My Biochem Flashcards
0
Q
Complex II Inhibitors
A
Carboxin
TTFA
Malonate
1
Q
Complex 1 inhibitors
A
Barbiturate
Amytal
Rotenone
Piercidin A
2
Q
Complex III Inhibitors
A
Antimycin A
Dimercaprol
3
Q
Complex IV Inhibitors
A
Sodium azide
Hydrogen sulfide
Cyanide
Carbon monoxide
4
Q
Complex v inhibitors
A
Oligomycin
5
Q
Uncouplers
A
Aspirin
Dinitrophenol
Thermogenin
6
Q
All complex mitochondrial disease
A
Fatal infantile mitochondrial myopathy
7
Q
Complex I mitochondrial disease
A
MELAS (mitochondrial encephalomyopathy, lactic acidosis, stroke like episodes)
8
Q
Complex II mitochondrial disease
A
Kearns-Sayre syndrome
9
Q
Complex III mitochondrial disease
A
Leber’s hereditary optic neuropathy
10
Q
Complex IV mitochondrial disease
A
Leigh’s disease
Ragged red muscle fiber disease
11
Q
Glut transporter for erythrocytes
A
1
12
Q
Glut transporter for brain
A
1 & 3
13
Q
Glut transporter for kidney
A
1, 2, 3
14
Q
Glut transporter for colon
A
1
15
Q
Glut transporter for placenta
A
1 & 3
16
Q
Glut transporter for liver
A
2
17
Q
Glut transporter for pancreatic B cell
A
2
18
Q
Glut transporter for small intestine
A
2, 5
19
Q
Glut transporter for heart
A
4
20
Q
Glut transporter for adipose
A
4
21
Q
Glut transporter for skeletal muscle
A
4
22
Q
Where does glycolysis occur?
A
Cytoplasm in all cells
23
Q
What is the substrate for glycolysis?
A
Glucose
24
What is the end product for glycolysis?
Pyruvate or lactate
25
Rate limiting step for Glycolysis
Fructose-6-Phosphate --(Phosphofructokinase 1)--> F-1,6-Bisphosphate)
26
Enzyme for energy expenditure step in Glycolysis
Hexokinase or Glucokinase
27
Energy production enzymes and steps in glycolysis
1,3 Bisphosphoglycerate --(Phosphoglycerate Kinase)--> 3 phosphoglycerate
PEP --(PEP Kinase)--> Pyruvate
28
Where is glucokinase present?
Liver parenchymal cells and islet cells of the pancreas
29
Activators for PFK1 vs PFK2
PFK1: Fructose-2,6-BP and AMP
PFK2: Well-fed state ^ Insulin and v Glucagon
30
Inhibitors for PFK1 vs PFK2
PFK1: ATP and citrate
PFK2: Starved state V insulin ^ Glucagon
31
Activator for PEP -> Pyruvate
Fructose-1,6-Bisphosphate
32
NADH2 production in glycolysis
Glyceraldehyde-3-P --(Glyceraldehyde-3-dehydrogenase)--> 1,3-Bisphosphoglycerate
33
Aerobic glycolysis shuttle used for the liver kidney and heart
Malate-asparte shuttle = 3 ATP
| mas Late but mas Astig!
34
Aerobic glycolysis shuttle used for the skeletal and brain
Glycerol Phosphate shuttle = 2 ATP
| needed FASTER thus less output
35
Major fate of pyruvate in RBCs, lens, cornea, kidney medulla, testes, and WBC
Anaerobic glycolysis
36
ATP yield for glycolysis in Aerobic vs Anaerobic
2 vs 6-8
37
How does arsenic poisoning disrupt the glycolytic cycle?
Arsenic:
- Inhibits pyruvate dehydrogenase by binding to lipoic acid
- Competes with inorganic P as a substrate for G-3-P dehydrogenase
38
Most common enzyme defiency in glycolysis?
Pyruvate kinase deficiency (X-linked recessive) which manifests as chronic hemolytic anemia. Decreased acetyl Coa in the brain causes psychomotor retardation and death.
Treated with Ketogenic diet
39
Four fates of pyruvate
Lactate, Ethanol, Acetyl CoA, Oxaloacetate
40
Co-enzymes of pyruvate dehydrogenase
```
Love Never Fails to Conquer
Lipoic Acid
NAD
FAD
Thiamine pyrophosphate
Coenzyme A
```
41
Where does the TCA cycle occur
In all cells with mitochondria in the mitochondrial matrix except succinate dehydrogenase which occurs in the inner membrane.
42
Rate limiting step in the TCA cycle
Isocitrate --(isocitrate dehydrogenase)--> a-ketoglutarate
43
What inhibits the conversion of citrate to isocitrate?
Fluroacetate (rat poison) inhibits aconitase
44
Where are the NADHs produced in the TCA cycle?
Isocitrate --(Isocitrate dehydrogenase)--> a-ketoglutarate + CO2
a-ketoglytarate --> Succinyl CoA + CO2
Malate -> Oxaloacetate
45
Where is the FADH2 produced in the TCA cycle?
Succinate --(succinate dehydrogenase)--> Fumarate
46
Which TCA intermediate could be used for heme synthesis and activation of ketone bodies in extra hepatic tissues?
Succinyl CoA
47
Which TCA intermediate can be used for gluconeogenesis?
Malate
48
Which TCA intermediate delivers acetyl CoA to the cytoplasm for Fatty synthesis via a shuttle mechanism?
Citrate
49
Is there hormonal control and new oxaloacetate production in the TCA cycle?
No
50
ATP yield for the TCA cycle from pyruvate? from Acetyl CoA?
From pyruvate: 15
| From Acetyl Coa: 12
51
Where does gluconeogenesis occur?
90% liver
10% kidney
During prolonged fasting, the kidneys contribute as much as 40%
Mitochondria and cytoplasm
52
Rate limiting step for gluconeogenesis
F-1,6-BP --(Fructose 1,6-bisphosphatase)--> F-6-P
53
Three processes that occur both in the mitochondria and the cytoplasm
Gluconeogenesis
Heme Synthesis
Urea synthesis
54
What cycle is responsible for the conversion of lactate to glucose?
Cori cycle
55
Energy expenditure of the Cori cycle
4 ATP
56
Enzymes required for the conversion of pyruvate to PEP in gluconeogenesis
PEP
^ Pyruvate carboxylase (Requires biotin and ATP)
Oxaloacetate
^ PEP Carboxykinase (Requires GTP)
Pyruvate
57
What are the 3 Carboxylase reactions? What is the required co-factor in these reactions?
1. Pyruvate -> OAA (Pyruvate carboxylase)
2. Acetyl CoA -> Malonyl CoA (Acetyl CoA Carboxylase)
3. Propionyl CoA -> Succinyl CoA (Propionyl CoA Carboxylase
58
Where does conversion of Glucose-6-P to Glucose occur? And why?
Liver and kidneys only since the muscle lacks G-6-Phosphatase
59
Energy expenditure for gluconeogenesis
1. Use of 4 ATPs
2. use of 2 GTPs
3. Oxidizes 2 NADH back to NAD+
60
Renal blood glucose threshold that leads to glucosuria
9.5-10.0 mmol/L
61
What are the three reactions that is favored by NADH usually due to alcoholism?
1. Pyruvate -> Lactate
2. OAA -> Malate
3. DHAP -> glycerol-3-phosphate
62
In pregnancy which hormone is resonsible for hyperinsulinemia? Insulin resistance?
Hyperinsulinemia: Estrogen (fasting hypoglycemia)
IR: HPL (Post prandial hyperglycemia)
64
Where is glycogen stored?
Liver 100g (6% of liver) and muscle 400g (<1% of muscle) only
65
Where does glycogenesis occur?
Cytosol of the Liver and the muscle
66
Substrates for glycogenesis
1. UDP Glucose
2. ATP and UTP
3. Glycogenin: primer protein core
67
Rate limiting step in glycogenesis
Elongation of glycogen (via glycogen synthase)
68
Steps in Glycogenesis
1. Glucose-6-P to Glucose-1-P (phosphoglucomutase)
2. Glucose-1-P to UDP-Glucose
3. Elongation of glycogen chains (Glycogen synthase)
4. Branching of glycogen (Branching enzyme a transglucosidase)
69
Where does glycogenolysis occur?
Cytosol of the liver and the muscle
70
How many glucose residues are there before a branch point or limit dextrin?
Four
71
Products of glycogenolysis
Glucose-1-P and Free glucose
Liver: Can release free glucose
Muscle: Glucose-6-P limited
72
Rate limiting step of glycogenolysis
Removal of glucose (Breaking of a[1->4] bonds via glycogen phosphorylase)
73
Steps in Glycogenolysis
1. Removal of glucose by glycogen phosphorylase
2. Glucantransferase transfers the a(1->4) -> a(1->4) limit dextrin
3. Amylo-a(1->6) removes a free glucose by breaking its bond)
4. Conversion of G-1-P to G-6-P via phosphoglucomutase
74
Glycogen storage disease that is due to G-6-phosphatase deficiency. Findings such as glycogen in liver and renal cells. Hypoglycemia + lactic acidosis and ketosis.
Type I - Von Gierke's
75
Glycogen storage disease that is due to acid maltase deficiency. There are findings such as glycogen in lysosomes, cardiomegaly, and heart failure.
Type II - Pompe's disease
76
Glycogen storage disease that is due to debranching enzyme deficiency. It is a milder form of type I
Type III - Cori's
77
Glycogen storage disease that is due to a skeletal muscle glycogen phosphorylase deficiency leading to glycogen in the muscle, muscle cramps + myoglobinuria but no lactic acidosis.
Type V - McArdle's
78
Where are Disaccharidases and trisaccharidases are located in? Can pancreatic amylases hydrolyze the sugars that these enzymes cover?
Brush border of the intestinal epithelium
| No, pancreatic amylases cannot
79
Steps in galactose metabolism
1. Galactose -> Galactose-1-P (Galactokinase or hexokinase)
2. Formation of UDP-Galactose + Glucose-1-P (Galactose-1-P uridyl transferase)
3. UDP-Galactose -> UDP-Glucose
80
Causes galactosemia and galactosuria
Galactokinase deficiency
81
Absence of galactose 1-P uridyltransferase, it is autosomal recessive, which leads to galactitol accumulation resulting in cataracts, hepatosplenomegaly and mental retardation
Classic Galactosemia
82
Important source of fructose
Disaccharide sucrose found in honey and fruits
| Sucrose if hydrolyzed by sucrase in the brush border
83
What sugar has the fastest metabolism and greatest yield of energy?
Fructose
84
Steps in fructose metabolism
1. Phosphorylation of fructose (Fructokinase or hexokinase)
| 2. Formation of DHAP and glyceraldehyde (Aldolase B)
85
Which pathways are the two aldolases found?
Aldolase A: Glycolysis
F-1,6-BP -> DHAP + Glycerol-3-P
Aldolase B: Fructose
F-1,6-P -> DHAP + Glyceraldehyde
86
Symptoms of essential dructosuria
Defect in fructokinase: benign and asymptompatic. Only blood and urine fructose is noted.
87
An autosomal recessive disease that is due to the deficiency in aldolase B. Symptoms noted are hypoglycemia, jaundice, cirrhosis, and vomiting.
Fructose intolerance leading to fructose 1-P accumulation which leads to decrease in phosphate, glycogenolysis, and gluconeogenesis. Treatment is decrease intake of sucrose and fructose.
88
Where is sorbitol dehydrogenase found? (Sorbitol -> Fructose)
Seminal vesicles since fructose is fuel for sperm
89
Where is aldose reductase found? (Glucose-> Sorbitol)
Lens, Schwann cells, liver, kidney, placenta, RBC, ovaries, seminal vesicles
90
What is the Pentose phosphate pathway for?
1. NADPH production
2. Ribose-5-phophate production for synthesis of nucleotides
3. Metabolic use of 5-carbon sugars
91
Where does the PPP occur?
Cytoplasm
92
NADPH provides electrons for
1. FA and steroid biosynthesis
2. Reduction of glutathione
3. Cytochrome P450
4. WBC respiratory burst
5. Nitric oxide synthesis
93
Rate limiting step for HMP or PPP?
Glucose-6-P -> 6-phosphogluconate
| Glucose-6-P dehydrogenase
94
Two phases of PPP
Phase 1: Oxidative (Irreversible) producing NADPH and Ribulose-5-P [via G-6-P dehydrogenase]
Phase 2: Non-oxidative (reversible) producing ribose-5-P, Glyceraldehyde-3-P, fructose-5-P [via transketolases requiring Thiamine]
95
Purpose of glutathione and how is it regenerated?
Reduced glutathione sequesters harmful H2O2 via glutathione peroxidase
Reduced glutathione is recreated using NAGPH via glutathione reductase
96
Most common disease producing enzyme abnormality in humans which involves decreased NADPH in RBCs and a decrease in glutathione reductase activity causing free radicals and peroxidases to accumulate?
Glucose 6-Phosphate deficiency
97
Most common precipitating factor for G6PD
Infection
98
Histologic pathognomonic features of G6PD
Heinz bodies and bite cells
99
a disease that is noted for its NADPH oxidase deficiency. It leads to severe, persistent and chronic pyogenic infections caused by catalase (+) bacteria
Chronic granulomatous disease
100
What enzyme activates fatty acid for metabolism use?
Fatty-acyl-CoA synthetase
101
Cofactor required for fatty acid activation
Vitamin B5 or Panthotenic acid
102
Energy required to activate fatty acid
2 ATP
103
What is the product formed in fatty acid synthesis?
Palmitate (16:0)
104
Where does fatty acid synthesis occur?
Cytosol
Major: Liver and lactating mammary glands
Minor: adipose tissue
105
Substrates for fatty acid synthesis
1 acetyl CoA
7 malonyl CoA
NADPH
ATP
106
Rate limiting step in fatty acid synthesis
Acetyl CoA + ATP -> malonyl CoA
| Enzyme: acetyl CoA carboxylase
107
Steps in fatty acid synthesis
1. Synthesis of cytoplasmic acetyl CoA (transfer of mitochondrial acetyl CoA to cytoplasm via citrate shuttle)
2. Acetyl CoA carboxylation to malonyl CoA (via acetyl CoA carboxylase with biotin) [+ insulin, citrate]
3. Assembly of palmitate (via fatty acid synthase and Vit B5)
108
Steps in palmitate assembly
1. Condensation
2. Reduction
3. Dehydration
4. Reduction
109
What is the fate of Palmitate after its production?
1. Further elongation in SER and mitochondria
| 2. Desaturated in the ER (but not past the 9th carbon)
110
Main storage form of fatty acids
Triacylglycerols
111
Where does TAG synthesis occur?
Liver and adipose tissue
112
Sources of glycerol-3-phosphate
1. DHAP from glycolysis (liver and adipose)
| 2. Phosphorylation of free glycerol (liver)
113
What enzyme is responsible for the release of free fatty acids from TAGs?
Hormone sensitive lipases
114
In the bloodstream fatty acids are always bound to?
Albumin
115
Hormone sensitive lipases can only release what free fatty acids stored in TAG?
C1 & 3 thus resulting in
TAG -> 2 free FA and 2-mono acyl glycerol
116
Where does B-oxidation of fatty acids occur
Mitochondria of all cells, but the fatty acid activation raft occurs in the Cytosol
Exception: RBC, kidney medulla, neurons, testes
117
Rate limiting step in B-oxidation
Fatty acyl CoA + carnitine -> fatty acyl carnitine + CoA
| Enzyme: carnitine acyl transferase I
118
Cutoff number of carbons that do not need a shuttle
Less than 12 carbons
119
Steps in the carnitine shuttle
1. Fatty acyl synthase activates the fatty acid
2. Carnitine acyl transferase 1 attaches to fatty acyl to carnitine in the outer mitochondrial membrane
3. Fatty acyl-carnitine is shuttle through the inner membrane
4. Carnitine acyl transferase-2 transfers fatty acyl group back to a CoA in the mitochondrial matrix
120
Steps in beta oxidation
1. Oxidation
2. Hydratiion
3. Oxidation
4. Thiolysis
121
Beta oxidation of fatty acids with an odd number of carbon atoms releases?
Propionyl CoA which is converted to methylmalonyl coa (requires B12) then to succinyl CoA
122
Which is responsible for the conversion of very long chain fatty acids?
Peroxisomes but if unsaturated it requires 3,2 enol-CoA isomerase
123
Energy yield in ATP of beta oxidation of palmitate
129 ATP
7 NADH= 21
7 FAD= 14
8 acetyl CoA= 96
Activation = -2
124
Intake of this compound depletes the body's NAD+ supply leading to accumulation Of fat in the liver
Alcohol
125
Type of carnitine deficiency which leads to impaired FA oxidation and ketogenesis with hypoglycemia?
CPT-1 deficiency
126
Type of carnitine deficiency which affects skeletal muscle and when severe the liver
CPT-2 deficiency
127
It is a disorder school results in decreased fatty acid oxidation. Without the ATP to support gluconeogenesis, hypoglycemia becomes profound which may eventually leads to SIDS. It is prevented by frequent feeding with high carbohydrate and low fat diet.
Medium-chain fatty acyl-CoA dehydrogenase (MCAD) deficiency
128
Associated with eating unripe fruit of the akee tree which contains hypoglycin thus activating MC and SC acyl CoA dehydrogenase
Jamaican vomiting sickness
129
Rare neurological disorder which results to the accumulation of phytanic acid found in plant food stuff which blocks Boxidation
Refsum disease
130
Cerebrohepatorenal syndrome resulting from the absence of peroxisomes in all tissues, it is characterized by liver dysfunction, jaundice, MR, weakness, hypotonia, and craniofacial dimorphism
Zellweger syndrome
131
Defect in peroxismal activation of VLCFA thus leading to its accumulation. Ssx: apathy, behavral change, then visual loss spasticity, ataxia. All due to the fact since VLCFA are found in myelin tissue.
X-lied adrenoleukodystrophy
132
Where does ketogenesis occur?
Liver mitochondria
133
Products of ketogenesis
Acetoacetate and B-hydroxybutyrate (fuel)
| Acetone (cannot be used as fuel)
134
Rate limiting step of ketogenesis
Acetoacetyl CoA + acetyl CoA --(HMG CoA synthase)--> HMG CoA
135
What are the initial products that lead to the formation of acetyl CoA in ketogenolysis?
B-hydroxybutyrate -> acetoacetate -> acetyl coa
136
What peripheral tissues can oxidize ketone bodes?
Those with mitochondria like the renal cortex, brain, and skeletal muscle
137
Why cant liver convert acetoacetate to acetyl CoA?
It lacks succinyl-CoA acetoacetyl-CoA reductase (thiophorase)
138
What is the Urine test for ketones? What ketone type does not it detect?
Nitroprusside test
Does not detect b-hydroxybutyrate
139
Which part of cholesterol can a fatty acid attach to form a cholesteryl ester?
Single hydroxyl group of carbon 3 of the alpha ring
140
Where does cholesterol synthesis occur?
All cells in the Cytosol and SER majority of which are found in the liver and intestines
141
Substrates of cholesterol synthesis
Acetyl CoA, NADPH, ATP
142
Rate limiting step in cholesterol synthesis
HMG CoA --(HMG CoA reductase)--> mevalonate
143
Steps in Cholestid synthesis
1. Biosynthesis of mevalonate
2. Formation of isoprenoid units
3. Isoprene unit is formed from 6 isoprenoid units
4. Formation of lanosterol
5. Formation of cholesterol
144
How is the cholesterol ring eliminated?
Through conversion to bile salts then secretion to bile
145
Bile acid synthesis, found in the liver and Cytosol, rate limiting enzyme is?
Cholesterol-7-a-hydroxylase
146
What are the primary bile acids?
Cholic acid
| Chenocholic acid
147
What are the two amino acids used in bile acid conjugation to form bile salts?
Taurine and glycine
148
What are the secondary bile acids?
Deoxycholic acid
| Lithocholic acid
149
Where does steroid hormone synthesis occur?
SER of the adrenal glands, ovaries and testes, and placenta
150
What is blocked by the drug aminogluthetimide?
The conversion of cholesterol to pregnenolone by desmolase
151
The enzyme responsible for the breakdown of TAG to FA and:
A) 2-MAG from diet
B) FREE glycerol from chylomicrons and VLDL
C) 2-MAG from adipose
A) pancreatic lipase
B) Lipoprotein lipase
C) hormone sensitive lipase
152
Lipoprotein with the largest percentage of TG
Chylomicrons
153
Lipoprotein with the largest percentage of cholesteryl esters
LDL
154
Chylomicrons transport TG and cholesterol from where to where?
Intestines to tissues
155
VLDL transports TG from where to where?
Liver to tissues
156
What apoprotein activates lipoprotein lipase?
APO-CII
157
What apolipoprotein uptakes remnants by the liver?
APO E
158
Apolipoprotein B-48 is used by chylomicrons which are created by the?
Epithelial cells
159
What apolipoprotein is secreted by the liver for VDL?
B-100
160
How does IDL become LDL?
By picking up cholesterol from HD!
161
Which apoprotein delivers cholesterol into cells?
LDL
162
Which apolipoprotein is used by HDL to activate lecithin cholesterol acyl transferase or LCAT to produce cholesterol esters?
APO-A1
163
Difference between Type II familial hypercholesterolemia and type IV familial hypertriglyceredemia?
The former has high LDL leader to xanthomas and xanthelasmas with increased risk of atherosclerosis and CHD
The latter has increased VLDL production leading to a triad of
1. DM type 2
2. CAD
3. Obesity
164
Phospholipid is composed of
DAG
Alcohol
Phosphodiester bond
165
Most abundant phospholipid which is important in nervous transmission
Phosphatidylcholine
166
Phospholipid playing a role in apoptosis
Phosphatidyl serine
167
Phospholipid that is a major component of surfactant?
Dipalmitoylphosphatidylcholine
168
Phospholipid reservoir for arachidonic acid in the membranes
Phosphatidylinositol
169
What phospholipid is essential in mitochondrial function which is also used as a non-troponemal test due to its ability to act as an antigen?
Cardiolipin
170
```
Composition of these glycolipids:
Ceramide
Cerebroside
Globoside
Ganglioside
Sulfatide
```
Ceramide: sphingosine + FA
```
Ceramide + ________
Glucose or galactose = Cerebroside
Oligosacchardide = Globoside
N-acetylneuramic acid = Ganglioside
Sulfated galactose = Sulfatide
```
171
Hexosaminidase a ficiency leading to Ssx like cherry red macula, MR, hypotonia
Tay-Sachs disease
172
A-galactosidase deficiency leading to 3Rs: recessive x-linked, rash, renal failure
Fabrys disease
173
B-glucosidase deficiency leading to hepatosplenomegaly and erosion of long bones
Gauchers dissease
174
Sphingomyelinase deficiency leading to hepatosplenomegaly
Nieman-pick disease
175
The set of all proteins expressed by an individual at a particular time
Proteome
176
Aims to identify the entire complement of proteins elaborated by a cell under diverse conditions
Proteomics
177
What amino acid is needed to form ALA in heme synthesis?
Glycine combined with succinyl CoA
178
Which amino acid carries nitrogen from the liver?
Alanine
179
Which amino acids are implicated in maple syrup disease
valine, lucine, isoleucine
180
What enzyme is responsible for the buildup of phenyl lactate, phenyl acetate, and phenylpyruvate?
Phenylalanine hydroxylase
181
What amino acid is the precursor for niacin, serotonin, and melatonin?
Serotonin
182
What is the amino acid precursor for homocysteine?
Methionine
183
What amino acid contributes to the fibrous structure of collagen and interrupts a-helices in globular proteins?
Proline
184
Increase of the combination of this Amino acid is responsible for the curly hair of people?
Cysteine + cysteine = cystine
185
Amino acids with sites for O-linked glycosylation in the Golgi apparatus?
Serine and threonine
186
Site for n-linked glycosylation in the ER
Asparagine
187
Amino acid deaminated by an enzyme which results in the formation of ammonia. This is the major carrier of nitrogen to the liver from peripheral tissues,
Glutaminase deaminates glutamine
188
Amino acid used in the determination for Folic acid deficiency. What is the test called?
Histidine used in the N-forminoglutamate excretion test
| Increased amounts of FIGu in urine by Folic acid deficient individuals after histindine intake
189
Precursor amino acid for creatinine, urea, nitric oxide
Arginine
190
Essential amino acids that cannot be synthesized by the body and must come from the diet
PVT TIM HALL always ARGues and never TYRes
Phenylalanine, valine, tryptophan, threonine' isoleucine, methionine, histidine, argenine, Leucine, Lysine
191
Heme is a complex of?
Protoporphorin IX and heme
192
What is the Bohr effect?
HBO2 + H+ HbH + O2
193
What is an oxidized for of HB (Fe 3+) that does not bind O2 readily which could lead to chocolate cyanosis ? It is treated with oral methylene blue or ascorbic acid up to IV methylene blue.
Methemoglobin
194
Hemoglobin bound to carbon monoxide instead of O2 leading to a cherry pink color.
Carboxyhemoglobin
195
HB bound to carbon dioxide is called
Carbaminohenoglobin
196
Classification of alpha and beta thalassemia
Alpha: silent carrier, a-thalassemia trait, Hb H disease, hydrops fetalis
Beta: B-thalassemia minor and major
197
Most frequently affected collagen in Ehler Danlos syndrome leading to hyper extensible skin, tendency to bleed, hyper mobile joints, and increased risk for berry aneurysms.
Collagen type 3
198
Collagen I mutation leading to bendable and easily fractured bones. Accompanied with blue sclerae, hearing loss, and dental imperfections.
Osteogenesis imperfecta
199
Vitamin C deficiency leading to decreased hydroxylation of collagen. This leads to sore spongy gums, loose teeth, poor wound healing, and petecchiae on skin and mucous membranes.
Scurvy
200
Type IV collagen defect leading to hematuria and ESRD
Alpert syndrome
201
Collagen defect leading to kinky hair due to a deficiency of copper required by lysyl oxidase to strengthen collagen fibers.
Menke syndrome
202
Skin breaking and blisters as a result for minor trauma. This disease is due to a defect in collage VII.
Epidermolysis bullosa
203
Like collagen elastin has pro line and Lysine but has little and no?
Hydroxyproline
| Hydroxylysine
204
Protein degradation mechanisms of nitrogen
Energy dependent ubiquitin-proteosome mechanism
| Non-energy dependent degradation enzyme
205
Phases in amino acid catabolism
First phase: removal of a-amino group forming ammonia and a corresponding ketoacid
Second phase: carbon skeletons of a-ketoacids are converted to common intermediates of energy producing metabolic pathwas
206
Two main steps in nitrogen removal from AA
1. Transamination
| 2. Oxidative deamination
207
Where does transamination occur?
All cells of the body
208
All but two amino acids transfer their amino groups to a-ketoglutarate except?
Lysine and threonine
209
What is the coenzyme for the two aminotransferases?
Pyridoxal phosphate (vitamin B6)
210
Oxidative deamination occurs where and for which amino acid only?
Liver and kidney
| Only glutamate
211
Glutamate is oxidized by glutamate dehydrogenases and deaminated to form ?
free ammonia which is used to make urea
212
What does the conversion of glutamate to a-ketoglutarate yield? What about vice versa?
Glutamate -> a ketoglutarate NH3 + NADH
| A ketoglutarate -> glutamate NADP+ + NH3
213
How is excess nitrogen removal from peripheral tissues removed?
1. Glutamine: via glutamate + ammonia (through Flutamide synthaetase)
2. Alanine: via glucose -> pyruvate + glutamate -> alanine cycle
214
Glutaminase deaminates glutamine to produce ammonium ion which is excreted from the body. Where are the two tissues this enzyme could be located?
Kidneys and small intestines
215
Another name for urea cycle
Ornithine cycle or krebs-henseleit cycle
216
What are the donors of the urea molecule?
1. NH3 from free ammonia
2. NH3 from aspartate
3. 1C and 1O from CO2
217
Reactions in the urea cycle
1. Formation of carbamoyl phosphate (via carbamoyl phosphate synthetase I)
2. Formation of citrulline (via Ornithine transcarbamoylase)
3. Synthesis of arginosuccinate (arginosuccinate synthetase)
4. Cleavage of arginosuccinate to form arginine (Arginosuccinase)
5. Arginine cleavage to yield urea and Ornithine (arginase)
218
Rate limiting step of urea cycle
Carbamoyl phosphate synthetase I
219
Energy requirement of urea cycle
4 ATP
220
Co factors of urea cycle
N-acetylglutamate
| Biotin
221
Hereditary hyperammonemia produces symptoms such as
Hyperammonemia, elevated blood glutamine, decreased BUN
| Parents with lethargy, vomiting, hyperventilation, convulsions, cerebral edema, coma, and death
222
Treatment for hereditary hyperammonemia
Low protein diet
| Administration of sodium benzoate or phenylpyruvate to capture and excrete excess nitrogen
223
Ketogenic carbon skeletons of AA
Leucine
Lysine
Yields acetoacetate or acetyl-coa/ acetoacetyl-coa
224
Ketogenic and glucogenic carbon skeletons of AA
```
WIFY
Phenylalanine
Isoleucine
Tryptophan
Tyrosine
```
Yields Ketogenic and glucose or glycogen by products
225
This amino acid acts as a raw material in the biosynthesis of Heme, purines, creatine
Glycine
226
This amino acid acts as a raw material in the biosynthesis of phospholipid, sphingolipid, purines, thymine
Serine
227
This amino acid acts as a raw material in the biosynthesis of GABA
Glutamate
228
This amino acid acts as a raw material in the biosynthesis of creatine, polyamines, nitric oxide
Arginine
229
This amino acid acts as a raw material in the biosynthesis of serotonin, NAD+, NADP+, melatonin
Tryptophan
230
This amino acid acts as a raw material in the biosynthesis of catecholamines, thyroid hormones, melanin
Tyrosine
231
3 hormones dependent on tyrosine
Thyroid hormones
Melanin
Catecholamines
232
Deficiency of homogenistic acid oxidase in the degrative pathway of tyrosine which results in urine turning to black on standing with dark connective tissues (ochronosis)
Alkaptonuria
233
Congenital deficiency due tyrosinase deficieny or defective tyrosine transporters which leads to an increased risk for skin cancer.
Albinism
234
Autosomal recessive disorder that may either be due to decreased methionine, increased cysteine, B6, and folate or decreased affinity for cystathione synthase. This results in mental retardation, osteoporosis, tall stature, lens subluxation, and atherosclerosis.
Homocystinuria
235
Common inherited defect of renal tubular amino acid transporter for its parent compound, Ornithine, Lysine, and arginine, in the PCT of the kidneys. It eventually precipitates and cause staghorn caliculi. What is its treatment?
Cystinuria is treated with acetazolamide to alkalinize the urine
236
The initial and last three steps of heme synthesis occurs in?
The mitochondria
237
Heme synthesis summary
1. Formation of ALA (via ALA synthase and B6)
2. Formation of porphobilinogen
3. Formation of uroporphyrinogen
4. Formation of heme
238
Lead inhibits what two steps in heme synthesis?
1. Introduction of Fe 2+ into protoporphyrin IX via ferrochelatase
2. Condensation of two ALA molecules by zinc containing ALA dehydratase
239
Where is B6 a cofactors of?
1. Heme synthesis
2. Synthesis of cystathionine from homocysteine
3. Transamination between alanine and a-ketoglutarate
240
Most common porphyria
Porphyria cutanea tarda
241
Which part of heme synthesis do these symptoms appear?
1. Photosensitivity
2. Neuropsychiatric symptoms
1. After ring formation
| 2. Before ring formation
242
Pyridoxine ficiency associated with isoniazid therapy results in this histopathologic finding
Sideroblastic anemia with ringed sideroblast
243
Poisoning due to this heavy metal leads to coar basophilic stippling of RBC, peripheral neuropathy, lines in gums, increas in urinary ALA and free erythrocytes porphorin
lead poisoning
244
Microcytic hypo chromic anemia is found in
IDA
Thalassemia
Lead poisoning
245
Megaloblastic anemia is found in
Folate or B12 deficiency
| Pernicious anemia
246
Normoyctic normochromic anemia is found in
Anemia of chronic kidney disease
| Blood loss
247
Increase in MCHC is found in
Hereditary spherocytosis
248
Summary of heme degradation
1. Formation of bilirubin
2. Uptake of bilirubin by the liver
3. Formation of bilirubin diglucoronide
4. Secretion of bilirubin into bile
5. Formation of urobilins in the intestine
249
Colors of biliverdin, bilirubin, urobilinogen, stercolin, urobilin
```
Biliverdin: green
Bilirubin: red orange
Urobilinogen: colorless
Stercolin: brown orange red
Urobilin: yellow
```
250
Examples of unconjugated hyperbilirubinemia
```
Hemolytic anemia
Physiologic jaundice
Crigler-najjar syndrome types I and II
Gilbert syndrome
Toxic hyperbilirubinemia
```
251
Examples of conjugated hyperbilirubinemia
Biliary tree obstruction
Dubin-Johnson syndrome
Rotor syndrome
252
What reaction measures total and direct bilirubin?
Van den bergs reaction
253
What enzyme activates fatty acid for metabolism use?
Fatty-acyl-CoA synthetase
254
Cofactor required for fatty acid activation
Vitamin B5 or Panthotenic acid
255
Energy required to activate fatty acid
2 ATP
256
What is the product formed in fatty acid synthesis?
Palmitate (16:0)
257
Where does fatty acid synthesis occur?
Cytosol
Major: Liver and lactating mammary glands
Minor: adipose tissue
258
Substrates for fatty acid synthesis
1 acetyl CoA
7 malonyl CoA
NADPH
ATP
259
Rate limiting step in fatty acid synthesis
Acetyl CoA + ATP -> malonyl CoA
| Enzyme: acetyl CoA carboxylase
260
Steps in fatty acid synthesis
1. Synthesis of cytoplasmic acetyl CoA (transfer of mitochondrial acetyl CoA to cytoplasm via citrate shuttle)
2. Acetyl CoA carboxylation to malonyl CoA (via acetyl CoA carboxylase with biotin) [+ insulin, citrate]
3. Assembly of palmitate (via fatty acid synthase and Vit B5)
261
Steps in palmitate assembly
1. Condensation
2. Reduction
3. Dehydration
4. Reduction
262
What is the fate of Palmitate after its production?
1. Further elongation in SER and mitochondria
| 2. Desaturated in the ER (but not past the 9th carbon)
263
Main storage form of fatty acids
Triacylglycerols
264
Where does TAG synthesis occur?
Liver and adipose tissue
265
Sources of glycerol-3-phosphate
1. DHAP from glycolysis (liver and adipose)
| 2. Phosphorylation of free glycerol (liver)
266
What enzyme is responsible for the release of free fatty acids from TAGs?
Hormone sensitive lipases
267
In the bloodstream fatty acids are always bound to?
Albumin
268
Hormone sensitive lipases can only release what free fatty acids stored in TAG?
C1 & 3 thus resulting in
TAG -> 2 free FA and 2-mono acyl glycerol
269
Where does B-oxidation of fatty acids occur
Mitochondria of all cells, but the fatty acid activation raft occurs in the Cytosol
Exception: RBC, kidney medulla, neurons, testes
270
Rate limiting step in B-oxidation
Fatty acyl CoA + carnitine -> fatty acyl carnitine + CoA
| Enzyme: carnitine acyl transferase I
271
Cutoff number of carbons that do not need a shuttle
Less than 12 carbons
272
Steps in the carnitine shuttle
1. Fatty acyl synthase activates the fatty acid
2. Carnitine acyl transferase 1 attaches to fatty acyl to carnitine in the outer mitochondrial membrane
3. Fatty acyl-carnitine is shuttle through the inner membrane
4. Carnitine acyl transferase-2 transfers fatty acyl group back to a CoA in the mitochondrial matrix
273
Steps in beta oxidation
1. Oxidation
2. Hydratiion
3. Oxidation
4. Thiolysis
274
Beta oxidation of fatty acids with an odd number of carbon atoms releases?
Propionyl CoA which is converted to methylmalonyl coa (requires B12) then to succinyl CoA
275
Which is responsible for the conversion of very long chain fatty acids?
Peroxisomes but if unsaturated it requires 3,2 enol-CoA isomerase
276
Energy yield in ATP of beta oxidation of palmitate
129 ATP
7 NADH= 21
7 FAD= 14
8 acetyl CoA= 96
Activation = -2
277
Intake of this compound depletes the body's NAD+ supply leading to accumulation Of fat in the liver
Alcohol
278
Type of carnitine deficiency which leads to impaired FA oxidation and ketogenesis with hypoglycemia?
CPT-1 deficiency
279
Type of carnitine deficiency which affects skeletal muscle and when severe the liver
CPT-2 deficiency
280
It is a disorder school results in decreased fatty acid oxidation. Without the ATP to support gluconeogenesis, hypoglycemia becomes profound which may eventually leads to SIDS. It is prevented by frequent feeding with high carbohydrate and low fat diet.
Medium-chain fatty acyl-CoA dehydrogenase (MCAD) deficiency
281
Associated with eating unripe fruit of the akee tree which contains hypoglycin thus activating MC and SC acyl CoA dehydrogenase
Jamaican vomiting sickness
282
Rare neurological disorder which results to the accumulation of phytanic acid found in plant food stuff which blocks Boxidation
Refsum disease
283
Cerebrohepatorenal syndrome resulting from the absence of peroxisomes in all tissues, it is characterized by liver dysfunction, jaundice, MR, weakness, hypotonia, and craniofacial dimorphism
Zellweger syndrome
284
Defect in peroxismal activation of VLCFA thus leading to its accumulation. Ssx: apathy, behavral change, then visual loss spasticity, ataxia. All due to the fact since VLCFA are found in myelin tissue.
X-lied adrenoleukodystrophy
285
Where does ketogenesis occur?
Liver mitochondria
286
Products of ketogenesis
Acetoacetate and B-hydroxybutyrate (fuel)
| Acetone (cannot be used as fuel)
287
Rate limiting step of ketogenesis
Acetoacetyl CoA + acetyl CoA --(HMG CoA synthase)--> HMG CoA
288
What are the initial products that lead to the formation of acetyl CoA in ketogenolysis?
B-hydroxybutyrate -> acetoacetate -> acetyl coa
289
What peripheral tissues can oxidize ketone bodes?
Those with mitochondria like the renal cortex, brain, and skeletal muscle
290
Why cant liver convert acetoacetate to acetyl CoA?
It lacks succinyl-CoA acetoacetyl-CoA reductase (thiophorase)
291
What is the Urine test for ketones? What ketone type does not it detect?
Nitroprusside test
Does not detect b-hydroxybutyrate
292
Which part of cholesterol can a fatty acid attach to form a cholesteryl ester?
Single hydroxyl group of carbon 3 of the alpha ring
293
Where does cholesterol synthesis occur?
All cells in the Cytosol and SER majority of which are found in the liver and intestines
294
Substrates of cholesterol synthesis
Acetyl CoA, NADPH, ATP
295
Rate limiting step in cholesterol synthesis
HMG CoA --(HMG CoA reductase)--> mevalonate
296
Steps in Cholestid synthesis
1. Biosynthesis of mevalonate
2. Formation of isoprenoid units
3. Isoprene unit is formed from 6 isoprenoid units
4. Formation of lanosterol
5. Formation of cholesterol
297
How is the cholesterol ring eliminated?
Through conversion to bile salts then secretion to bile
298
Bile acid synthesis, found in the liver and Cytosol, rate limiting enzyme is?
Cholesterol-7-a-hydroxylase
299
What are the primary bile acids?
Cholic acid
| Chenocholic acid
300
What are the two amino acids used in bile acid conjugation to form bile salts?
Taurine and glycine
301
What are the secondary bile acids?
Deoxycholic acid
| Lithocholic acid
302
Where does steroid hormone synthesis occur?
SER of the adrenal glands, ovaries and testes, and placenta
303
What is blocked by the drug aminogluthetimide?
The conversion of cholesterol to pregnenolone by desmolase
304
The enzyme responsible for the breakdown of TAG to FA and:
A) 2-MAG from diet
B) FREE glycerol from chylomicrons and VLDL
C) 2-MAG from adipose
A) pancreatic lipase
B) Lipoprotein lipase
C) hormone sensitive lipase
305
Lipoprotein with the largest percentage of TG
Chylomicrons
306
Lipoprotein with the largest percentage of cholesteryl esters
LDL
307
Chylomicrons transport TG and cholesterol from where to where?
Intestines to tissues
308
VLDL transports TG from where to where?
Liver to tissues
309
What apoprotein activates lipoprotein lipase?
APO-CII
310
What apolipoprotein uptakes remnants by the liver?
APO E
311
Apolipoprotein B-48 is used by chylomicrons which are created by the?
Epithelial cells
312
What apolipoprotein is secreted by the liver for VDL?
B-100
313
How does IDL become LDL?
By picking up cholesterol from HD!
314
Which apoprotein delivers cholesterol into cells?
LDL
315
Which apolipoprotein is used by HDL to activate lecithin cholesterol acyl transferase or LCAT to produce cholesterol esters?
APO-A1
316
Difference between Type II familial hypercholesterolemia and type IV familial hypertriglyceredemia?
The former has high LDL leader to xanthomas and xanthelasmas with increased risk of atherosclerosis and CHD
The latter has increased VLDL production leading to a triad of
1. DM type 2
2. CAD
3. Obesity
317
Phospholipid is composed of
DAG
Alcohol
Phosphodiester bond
318
Most abundant phospholipid which is important in nervous transmission
Phosphatidylcholine
319
Phospholipid playing a role in apoptosis
Phosphatidyl serine
320
Phospholipid that is a major component of surfactant?
Dipalmitoylphosphatidylcholine
321
Phospholipid reservoir for arachidonic acid in the membranes
Phosphatidylinositol
322
What phospholipid is essential in mitochondrial function which is also used as a non-troponemal test due to its ability to act as an antigen?
Cardiolipin
323
```
Composition of these glycolipids:
Ceramide
Cerebroside
Globoside
Ganglioside
Sulfatide
```
Ceramide: sphingosine + FA
```
Ceramide + ________
Glucose or galactose = Cerebroside
Oligosacchardide = Globoside
N-acetylneuramic acid = Ganglioside
Sulfated galactose = Sulfatide
```
324
Hexosaminidase a ficiency leading to Ssx like cherry red macula, MR, hypotonia
Tay-Sachs disease
325
A-galactosidase deficiency leading to 3Rs: recessive x-linked, rash, renal failure
Fabrys disease
326
B-glucosidase deficiency leading to hepatosplenomegaly and erosion of long bones
Gauchers dissease
327
Sphingomyelinase deficiency leading to hepatosplenomegaly
Nieman-pick disease
328
The set of all proteins expressed by an individual at a particular time
Proteome
329
Aims to identify the entire complement of proteins elaborated by a cell under diverse conditions
Proteomics
330
What amino acid is needed to form ALA in heme synthesis?
Glycine combined with succinyl CoA
331
Which amino acid carries nitrogen from the liver?
Alanine
332
Which amino acids are implicated in maple syrup disease
valine, lucine, isoleucine
333
What enzyme is responsible for the buildup of phenyl lactate, phenyl acetate, and phenylpyruvate?
Phenylalanine hydroxylase
334
What amino acid is the precursor for niacin, serotonin, and melatonin?
Serotonin
335
What is the amino acid precursor for homocysteine?
Methionine
336
What amino acid contributes to the fibrous structure of collagen and interrupts a-helices in globular proteins?
Proline
337
Increase of the combination of this Amino acid is responsible for the curly hair of people?
Cysteine + cysteine = cystine
338
Amino acids with sites for O-linked glycosylation in the Golgi apparatus?
Serine and threonine
339
Site for n-linked glycosylation in the ER
Asparagine
340
Amino acid deaminated by an enzyme which results in the formation of ammonia. This is the major carrier of nitrogen to the liver from peripheral tissues,
Glutaminase deaminates glutamine
341
Amino acid used in the determination for Folic acid deficiency. What is the test called?
Histidine used in the N-forminoglutamate excretion test
| Increased amounts of FIGu in urine by Folic acid deficient individuals after histindine intake
342
Precursor amino acid for creatinine, urea, nitric oxide
Arginine
343
Essential amino acids that cannot be synthesized by the body and must come from the diet
PVT TIM HALL always ARGues and never TYRes
Phenylalanine, valine, tryptophan, threonine' isoleucine, methionine, histidine, argenine, Leucine, Lysine
344
Heme is a complex of?
Protoporphorin IX and heme
345
What is the Bohr effect?
HBO2 + H+ HbH + O2
346
What is an oxidized for of HB (Fe 3+) that does not bind O2 readily which could lead to chocolate cyanosis ? It is treated with oral methylene blue or ascorbic acid up to IV methylene blue.
Methemoglobin
347
Hemoglobin bound to carbon monoxide instead of O2 leading to a cherry pink color.
Carboxyhemoglobin
348
HB bound to carbon dioxide is called
Carbaminohenoglobin
349
Classification of alpha and beta thalassemia
Alpha: silent carrier, a-thalassemia trait, Hb H disease, hydrops fetalis
Beta: B-thalassemia minor and major
350
Most frequently affected collagen in Ehler Danlos syndrome leading to hyper extensible skin, tendency to bleed, hyper mobile joints, and increased risk for berry aneurysms.
Collagen type 3
351
Collagen I mutation leading to bendable and easily fractured bones. Accompanied with blue sclerae, hearing loss, and dental imperfections.
Osteogenesis imperfecta
352
Vitamin C deficiency leading to decreased hydroxylation of collagen. This leads to sore spongy gums, loose teeth, poor wound healing, and petecchiae on skin and mucous membranes.
Scurvy
353
Type IV collagen defect leading to hematuria and ESRD
Alpert syndrome
354
Collagen defect leading to kinky hair due to a deficiency of copper required by lysyl oxidase to strengthen collagen fibers.
Menke syndrome
355
Skin breaking and blisters as a result for minor trauma. This disease is due to a defect in collage VII.
Epidermolysis bullosa
356
Like collagen elastin has pro line and Lysine but has little and no?
Hydroxyproline
| Hydroxylysine
357
Protein degradation mechanisms of nitrogen
Energy dependent ubiquitin-proteosome mechanism
| Non-energy dependent degradation enzyme
358
Phases in amino acid catabolism
First phase: removal of a-amino group forming ammonia and a corresponding ketoacid
Second phase: carbon skeletons of a-ketoacids are converted to common intermediates of energy producing metabolic pathwas
359
Two main steps in nitrogen removal from AA
1. Transamination
| 2. Oxidative deamination
360
Where does transamination occur?
All cells of the body
361
All but two amino acids transfer their amino groups to a-ketoglutarate except?
Lysine and threonine
362
What is the coenzyme for the two aminotransferases?
Pyridoxal phosphate (vitamin B6)
363
Oxidative deamination occurs where and for which amino acid only?
Liver and kidney
| Only glutamate
364
Glutamate is oxidized by glutamate dehydrogenases and deaminated to form ?
free ammonia which is used to make urea
365
What does the conversion of glutamate to a-ketoglutarate yield? What about vice versa?
Glutamate -> a ketoglutarate NH3 + NADH
| A ketoglutarate -> glutamate NADP+ + NH3
366
How is excess nitrogen removal from peripheral tissues removed?
1. Glutamine: via glutamate + ammonia (through Flutamide synthaetase)
2. Alanine: via glucose -> pyruvate + glutamate -> alanine cycle
367
Glutaminase deaminates glutamine to produce ammonium ion which is excreted from the body. Where are the two tissues this enzyme could be located?
Kidneys and small intestines
368
Another name for urea cycle
Ornithine cycle or krebs-henseleit cycle
369
What are the donors of the urea molecule?
1. NH3 from free ammonia
2. NH3 from aspartate
3. 1C and 1O from CO2
370
Reactions in the urea cycle
1. Formation of carbamoyl phosphate (via carbamoyl phosphate synthetase I)
2. Formation of citrulline (via Ornithine transcarbamoylase)
3. Synthesis of arginosuccinate (arginosuccinate synthetase)
4. Cleavage of arginosuccinate to form arginine (Arginosuccinase)
5. Arginine cleavage to yield urea and Ornithine (arginase)
371
Rate limiting step of urea cycle
Carbamoyl phosphate synthetase I
372
Energy requirement of urea cycle
4 ATP
373
Co factors of urea cycle
N-acetylglutamate
| Biotin
374
Hereditary hyperammonemia produces symptoms such as
Hyperammonemia, elevated blood glutamine, decreased BUN
| Parents with lethargy, vomiting, hyperventilation, convulsions, cerebral edema, coma, and death
375
Treatment for hereditary hyperammonemia
Low protein diet
| Administration of sodium benzoate or phenylpyruvate to capture and excrete excess nitrogen
376
What reaction measures total and direct bilirubin?
Van den bergs reaction
377
Examples of conjugated hyperbilirubinemia
Biliary tree obstruction
Dubin-Johnson syndrome
Rotor syndrome
378
Examples of unconjugated hyperbilirubinemia
```
Hemolytic anemia
Physiologic jaundice
Crigler-najjar syndrome types I and II
Gilbert syndrome
Toxic hyperbilirubinemia
```
379
Colors of biliverdin, bilirubin, urobilinogen, stercolin, urobilin
```
Biliverdin: green
Bilirubin: red orange
Urobilinogen: colorless
Stercolin: brown orange red
Urobilin: yellow
```
380
Summary of heme degradation
1. Formation of bilirubin
2. Uptake of bilirubin by the liver
3. Formation of bilirubin diglucoronide
4. Secretion of bilirubin into bile
5. Formation of urobilins in the intestine
381
Increase in MCHC is found in
Hereditary spherocytosis
382
Normoyctic normochromic anemia is found in
Anemia of chronic kidney disease
| Blood loss
383
Megaloblastic anemia is found in
Folate or B12 deficiency
| Pernicious anemia
384
Microcytic hypo chromic anemia is found in
IDA
Thalassemia
Lead poisoning
385
Poisoning due to this heavy metal leads to coar basophilic stippling of RBC, peripheral neuropathy, lines in gums, increas in urinary ALA and free erythrocytes porphorin
lead poisoning
386
Pyridoxine ficiency associated with isoniazid therapy results in this histopathologic finding
Sideroblastic anemia with ringed sideroblast
387
Which part of heme synthesis do these symptoms appear?
1. Photosensitivity
2. Neuropsychiatric symptoms
1. After ring formation
| 2. Before ring formation
388
Most common porphyria
Porphyria cutanea tarda
389
Where is B6 a cofactors of?
1. Heme synthesis
2. Synthesis of cystathionine from homocysteine
3. Transamination between alanine and a-ketoglutarate
390
Lead inhibits what two steps in heme synthesis?
1. Introduction of Fe 2+ into protoporphyrin IX via ferrochelatase
2. Condensation of two ALA molecules by zinc containing ALA dehydratase
391
Heme synthesis summary
1. Formation of ALA (via ALA synthase and B6)
2. Formation of porphobilinogen
3. Formation of uroporphyrinogen
4. Formation of heme
392
The initial and last three steps of heme synthesis occurs in?
The mitochondria
393
Common inherited defect of renal tubular amino acid transporter for its parent compound, Ornithine, Lysine, and arginine, in the PCT of the kidneys. It eventually precipitates and cause staghorn caliculi. What is its treatment?
Cystinuria is treated with acetazolamide to alkalinize the urine
394
Autosomal recessive disorder that may either be due to decreased methionine, increased cysteine, B6, and folate or decreased affinity for cystathione synthase. This results in mental retardation, osteoporosis, tall stature, lens subluxation, and atherosclerosis.
Homocystinuria
395
Congenital deficiency due tyrosinase deficieny or defective tyrosine transporters which leads to an increased risk for skin cancer.
Albinism
396
Deficiency of homogenistic acid oxidase in the degrative pathway of tyrosine which results in urine turning to black on standing with dark connective tissues (ochronosis)
Alkaptonuria
397
3 hormones dependent on tyrosine
Thyroid hormones
Melanin
Catecholamines
398
This amino acid acts as a raw material in the biosynthesis of catecholamines, thyroid hormones, melanin
Tyrosine
399
This amino acid acts as a raw material in the biosynthesis of serotonin, NAD+, NADP+, melatonin
Tryptophan
400
This amino acid acts as a raw material in the biosynthesis of creatine, polyamines, nitric oxide
Arginine
401
This amino acid acts as a raw material in the biosynthesis of GABA
Glutamate
402
This amino acid acts as a raw material in the biosynthesis of phospholipid, sphingolipid, purines, thymine
Serine
403
This amino acid acts as a raw material in the biosynthesis of Heme, purines, creatine
Glycine
404
Ketogenic and glucogenic carbon skeletons of AA
```
WIFY
Phenylalanine
Isoleucine
Tryptophan
Tyrosine
```
Yields Ketogenic and glucose or glycogen by products
405
Ketogenic carbon skeletons of AA
Leucine
Lysine
Yields acetoacetate or acetyl-coa/ acetoacetyl-coa
406
What enzyme activates fatty acid for metabolism use?
Fatty-acyl-CoA synthetase
407
Cofactor required for fatty acid activation
Vitamin B5 or Panthotenic acid
408
Energy required to activate fatty acid
2 ATP
409
What is the product formed in fatty acid synthesis?
Palmitate (16:0)
410
Where does fatty acid synthesis occur?
Cytosol
Major: Liver and lactating mammary glands
Minor: adipose tissue
411
Substrates for fatty acid synthesis
1 acetyl CoA
7 malonyl CoA
NADPH
ATP
412
Rate limiting step in fatty acid synthesis
Acetyl CoA + ATP -> malonyl CoA
| Enzyme: acetyl CoA carboxylase
413
Steps in fatty acid synthesis
1. Synthesis of cytoplasmic acetyl CoA (transfer of mitochondrial acetyl CoA to cytoplasm via citrate shuttle)
2. Acetyl CoA carboxylation to malonyl CoA (via acetyl CoA carboxylase with biotin) [+ insulin, citrate]
3. Assembly of palmitate (via fatty acid synthase and Vit B5)
414
Steps in palmitate assembly
1. Condensation
2. Reduction
3. Dehydration
4. Reduction
415
What is the fate of Palmitate after its production?
1. Further elongation in SER and mitochondria
| 2. Desaturated in the ER (but not past the 9th carbon)
416
Main storage form of fatty acids
Triacylglycerols
417
Where does TAG synthesis occur?
Liver and adipose tissue
418
Sources of glycerol-3-phosphate
1. DHAP from glycolysis (liver and adipose)
| 2. Phosphorylation of free glycerol (liver)
419
What enzyme is responsible for the release of free fatty acids from TAGs?
Hormone sensitive lipases
420
In the bloodstream fatty acids are always bound to?
Albumin
421
Hormone sensitive lipases can only release what free fatty acids stored in TAG?
C1 & 3 thus resulting in
TAG -> 2 free FA and 2-mono acyl glycerol
422
Where does B-oxidation of fatty acids occur
Mitochondria of all cells, but the fatty acid activation raft occurs in the Cytosol
Exception: RBC, kidney medulla, neurons, testes
423
Rate limiting step in B-oxidation
Fatty acyl CoA + carnitine -> fatty acyl carnitine + CoA
| Enzyme: carnitine acyl transferase I
424
Cutoff number of carbons that do not need a shuttle
Less than 12 carbons
425
Steps in the carnitine shuttle
1. Fatty acyl synthase activates the fatty acid
2. Carnitine acyl transferase 1 attaches to fatty acyl to carnitine in the outer mitochondrial membrane
3. Fatty acyl-carnitine is shuttle through the inner membrane
4. Carnitine acyl transferase-2 transfers fatty acyl group back to a CoA in the mitochondrial matrix
426
Steps in beta oxidation
1. Oxidation
2. Hydratiion
3. Oxidation
4. Thiolysis
427
Beta oxidation of fatty acids with an odd number of carbon atoms releases?
Propionyl CoA which is converted to methylmalonyl coa (requires B12) then to succinyl CoA
428
Which is responsible for the conversion of very long chain fatty acids?
Peroxisomes but if unsaturated it requires 3,2 enol-CoA isomerase
429
Energy yield in ATP of beta oxidation of palmitate
129 ATP
7 NADH= 21
7 FAD= 14
8 acetyl CoA= 96
Activation = -2
430
Intake of this compound depletes the body's NAD+ supply leading to accumulation Of fat in the liver
Alcohol
431
Type of carnitine deficiency which leads to impaired FA oxidation and ketogenesis with hypoglycemia?
CPT-1 deficiency
432
Type of carnitine deficiency which affects skeletal muscle and when severe the liver
CPT-2 deficiency
433
It is a disorder school results in decreased fatty acid oxidation. Without the ATP to support gluconeogenesis, hypoglycemia becomes profound which may eventually leads to SIDS. It is prevented by frequent feeding with high carbohydrate and low fat diet.
Medium-chain fatty acyl-CoA dehydrogenase (MCAD) deficiency
434
Associated with eating unripe fruit of the akee tree which contains hypoglycin thus activating MC and SC acyl CoA dehydrogenase
Jamaican vomiting sickness
435
Rare neurological disorder which results to the accumulation of phytanic acid found in plant food stuff which blocks Boxidation
Refsum disease
436
Cerebrohepatorenal syndrome resulting from the absence of peroxisomes in all tissues, it is characterized by liver dysfunction, jaundice, MR, weakness, hypotonia, and craniofacial dimorphism
Zellweger syndrome
437
Defect in peroxismal activation of VLCFA thus leading to its accumulation. Ssx: apathy, behavral change, then visual loss spasticity, ataxia. All due to the fact since VLCFA are found in myelin tissue.
X-lied adrenoleukodystrophy
438
Where does ketogenesis occur?
Liver mitochondria
439
Products of ketogenesis
Acetoacetate and B-hydroxybutyrate (fuel)
| Acetone (cannot be used as fuel)
440
Rate limiting step of ketogenesis
Acetoacetyl CoA + acetyl CoA --(HMG CoA synthase)--> HMG CoA
441
What are the initial products that lead to the formation of acetyl CoA in ketogenolysis?
B-hydroxybutyrate -> acetoacetate -> acetyl coa
442
What peripheral tissues can oxidize ketone bodes?
Those with mitochondria like the renal cortex, brain, and skeletal muscle
443
Why cant liver convert acetoacetate to acetyl CoA?
It lacks succinyl-CoA acetoacetyl-CoA reductase (thiophorase)
444
What is the Urine test for ketones? What ketone type does not it detect?
Nitroprusside test
Does not detect b-hydroxybutyrate
445
Which part of cholesterol can a fatty acid attach to form a cholesteryl ester?
Single hydroxyl group of carbon 3 of the alpha ring
446
Where does cholesterol synthesis occur?
All cells in the Cytosol and SER majority of which are found in the liver and intestines
447
Substrates of cholesterol synthesis
Acetyl CoA, NADPH, ATP
448
Rate limiting step in cholesterol synthesis
HMG CoA --(HMG CoA reductase)--> mevalonate
449
Steps in Cholestid synthesis
1. Biosynthesis of mevalonate
2. Formation of isoprenoid units
3. Isoprene unit is formed from 6 isoprenoid units
4. Formation of lanosterol
5. Formation of cholesterol
450
How is the cholesterol ring eliminated?
Through conversion to bile salts then secretion to bile
451
Bile acid synthesis, found in the liver and Cytosol, rate limiting enzyme is?
Cholesterol-7-a-hydroxylase
452
What are the primary bile acids?
Cholic acid
| Chenocholic acid
453
What are the two amino acids used in bile acid conjugation to form bile salts?
Taurine and glycine
454
What are the secondary bile acids?
Deoxycholic acid
| Lithocholic acid
455
Where does steroid hormone synthesis occur?
SER of the adrenal glands, ovaries and testes, and placenta
456
What is blocked by the drug aminogluthetimide?
The conversion of cholesterol to pregnenolone by desmolase
457
The enzyme responsible for the breakdown of TAG to FA and:
A) 2-MAG from diet
B) FREE glycerol from chylomicrons and VLDL
C) 2-MAG from adipose
A) pancreatic lipase
B) Lipoprotein lipase
C) hormone sensitive lipase
458
Lipoprotein with the largest percentage of TG
Chylomicrons
459
Lipoprotein with the largest percentage of cholesteryl esters
LDL
460
Chylomicrons transport TG and cholesterol from where to where?
Intestines to tissues
461
VLDL transports TG from where to where?
Liver to tissues
462
What apoprotein activates lipoprotein lipase?
APO-CII
463
What apolipoprotein uptakes remnants by the liver?
APO E
464
Apolipoprotein B-48 is used by chylomicrons which are created by the?
Epithelial cells
465
What apolipoprotein is secreted by the liver for VDL?
B-100
466
How does IDL become LDL?
By picking up cholesterol from HD!
467
Which apoprotein delivers cholesterol into cells?
LDL
468
Which apolipoprotein is used by HDL to activate lecithin cholesterol acyl transferase or LCAT to produce cholesterol esters?
APO-A1
469
Difference between Type II familial hypercholesterolemia and type IV familial hypertriglyceredemia?
The former has high LDL leader to xanthomas and xanthelasmas with increased risk of atherosclerosis and CHD
The latter has increased VLDL production leading to a triad of
1. DM type 2
2. CAD
3. Obesity
470
Phospholipid is composed of
DAG
Alcohol
Phosphodiester bond
471
Most abundant phospholipid which is important in nervous transmission
Phosphatidylcholine
472
Phospholipid playing a role in apoptosis
Phosphatidyl serine
473
Phospholipid that is a major component of surfactant?
Dipalmitoylphosphatidylcholine
474
Phospholipid reservoir for arachidonic acid in the membranes
Phosphatidylinositol
475
What phospholipid is essential in mitochondrial function which is also used as a non-troponemal test due to its ability to act as an antigen?
Cardiolipin
476
```
Composition of these glycolipids:
Ceramide
Cerebroside
Globoside
Ganglioside
Sulfatide
```
Ceramide: sphingosine + FA
```
Ceramide + ________
Glucose or galactose = Cerebroside
Oligosacchardide = Globoside
N-acetylneuramic acid = Ganglioside
Sulfated galactose = Sulfatide
```
477
Hexosaminidase a ficiency leading to Ssx like cherry red macula, MR, hypotonia
Tay-Sachs disease
478
A-galactosidase deficiency leading to 3Rs: recessive x-linked, rash, renal failure
Fabrys disease
479
B-glucosidase deficiency leading to hepatosplenomegaly and erosion of long bones
Gauchers dissease
480
Sphingomyelinase deficiency leading to hepatosplenomegaly
Nieman-pick disease
481
The set of all proteins expressed by an individual at a particular time
Proteome
482
Aims to identify the entire complement of proteins elaborated by a cell under diverse conditions
Proteomics
483
What amino acid is needed to form ALA in heme synthesis?
Glycine combined with succinyl CoA
484
Which amino acid carries nitrogen from the liver?
Alanine
485
Which amino acids are implicated in maple syrup disease
valine, lucine, isoleucine
486
What enzyme is responsible for the buildup of phenyl lactate, phenyl acetate, and phenylpyruvate?
Phenylalanine hydroxylase
487
What amino acid is the precursor for niacin, serotonin, and melatonin?
Serotonin
488
What is the amino acid precursor for homocysteine?
Methionine
489
What amino acid contributes to the fibrous structure of collagen and interrupts a-helices in globular proteins?
Proline
490
Increase of the combination of this Amino acid is responsible for the curly hair of people?
Cysteine + cysteine = cystine
491
Amino acids with sites for O-linked glycosylation in the Golgi apparatus?
Serine and threonine
492
Site for n-linked glycosylation in the ER
Asparagine
493
Amino acid deaminated by an enzyme which results in the formation of ammonia. This is the major carrier of nitrogen to the liver from peripheral tissues,
Glutaminase deaminates glutamine
494
Amino acid used in the determination for Folic acid deficiency. What is the test called?
Histidine used in the N-forminoglutamate excretion test
| Increased amounts of FIGu in urine by Folic acid deficient individuals after histindine intake
495
Precursor amino acid for creatinine, urea, nitric oxide
Arginine
496
Essential amino acids that cannot be synthesized by the body and must come from the diet
PVT TIM HALL always ARGues and never TYRes
Phenylalanine, valine, tryptophan, threonine' isoleucine, methionine, histidine, argenine, Leucine, Lysine
497
Heme is a complex of?
Protoporphorin IX and heme
498
What is the Bohr effect?
HBO2 + H+ HbH + O2
499
What is an oxidized for of HB (Fe 3+) that does not bind O2 readily which could lead to chocolate cyanosis ? It is treated with oral methylene blue or ascorbic acid up to IV methylene blue.
Methemoglobin
500
Hemoglobin bound to carbon monoxide instead of O2 leading to a cherry pink color.
Carboxyhemoglobin
501
HB bound to carbon dioxide is called
Carbaminohenoglobin
502
Classification of alpha and beta thalassemia
Alpha: silent carrier, a-thalassemia trait, Hb H disease, hydrops fetalis
Beta: B-thalassemia minor and major
503
Most frequently affected collagen in Ehler Danlos syndrome leading to hyper extensible skin, tendency to bleed, hyper mobile joints, and increased risk for berry aneurysms.
Collagen type 3
504
Collagen I mutation leading to bendable and easily fractured bones. Accompanied with blue sclerae, hearing loss, and dental imperfections.
Osteogenesis imperfecta
505
Vitamin C deficiency leading to decreased hydroxylation of collagen. This leads to sore spongy gums, loose teeth, poor wound healing, and petecchiae on skin and mucous membranes.
Scurvy
506
Type IV collagen defect leading to hematuria and ESRD
Alpert syndrome
507
Collagen defect leading to kinky hair due to a deficiency of copper required by lysyl oxidase to strengthen collagen fibers.
Menke syndrome
508
Skin breaking and blisters as a result for minor trauma. This disease is due to a defect in collage VII.
Epidermolysis bullosa
509
Like collagen elastin has pro line and Lysine but has little and no?
Hydroxyproline
| Hydroxylysine
510
Protein degradation mechanisms of nitrogen
Energy dependent ubiquitin-proteosome mechanism
| Non-energy dependent degradation enzyme
511
Phases in amino acid catabolism
First phase: removal of a-amino group forming ammonia and a corresponding ketoacid
Second phase: carbon skeletons of a-ketoacids are converted to common intermediates of energy producing metabolic pathwas
512
Two main steps in nitrogen removal from AA
1. Transamination
| 2. Oxidative deamination
513
Where does transamination occur?
All cells of the body
514
All but two amino acids transfer their amino groups to a-ketoglutarate except?
Lysine and threonine
515
What is the coenzyme for the two aminotransferases?
Pyridoxal phosphate (vitamin B6)
516
Oxidative deamination occurs where and for which amino acid only?
Liver and kidney
| Only glutamate
517
Glutamate is oxidized by glutamate dehydrogenases and deaminated to form ?
free ammonia which is used to make urea
518
What does the conversion of glutamate to a-ketoglutarate yield? What about vice versa?
Glutamate -> a ketoglutarate NH3 + NADH
| A ketoglutarate -> glutamate NADP+ + NH3
519
How is excess nitrogen removal from peripheral tissues removed?
1. Glutamine: via glutamate + ammonia (through Flutamide synthaetase)
2. Alanine: via glucose -> pyruvate + glutamate -> alanine cycle
520
Glutaminase deaminates glutamine to produce ammonium ion which is excreted from the body. Where are the two tissues this enzyme could be located?
Kidneys and small intestines
521
Another name for urea cycle
Ornithine cycle or krebs-henseleit cycle
522
What are the donors of the urea molecule?
1. NH3 from free ammonia
2. NH3 from aspartate
3. 1C and 1O from CO2
523
Reactions in the urea cycle
1. Formation of carbamoyl phosphate (via carbamoyl phosphate synthetase I)
2. Formation of citrulline (via Ornithine transcarbamoylase)
3. Synthesis of arginosuccinate (arginosuccinate synthetase)
4. Cleavage of arginosuccinate to form arginine (Arginosuccinase)
5. Arginine cleavage to yield urea and Ornithine (arginase)
524
Rate limiting step of urea cycle
Carbamoyl phosphate synthetase I
525
Energy requirement of urea cycle
4 ATP
526
Co factors of urea cycle
N-acetylglutamate
| Biotin
527
Hereditary hyperammonemia produces symptoms such as
Hyperammonemia, elevated blood glutamine, decreased BUN
| Parents with lethargy, vomiting, hyperventilation, convulsions, cerebral edema, coma, and death
528
Treatment for hereditary hyperammonemia
Low protein diet
| Administration of sodium benzoate or phenylpyruvate to capture and excrete excess nitrogen
529
Ketogenic carbon skeletons of AA
Leucine
Lysine
Yields acetoacetate or acetyl-coa/ acetoacetyl-coa
530
Ketogenic and glucogenic carbon skeletons of AA
```
WIFY
Phenylalanine
Isoleucine
Tryptophan
Tyrosine
```
Yields Ketogenic and glucose or glycogen by products
531
This amino acid acts as a raw material in the biosynthesis of Heme, purines, creatine
Glycine
532
This amino acid acts as a raw material in the biosynthesis of phospholipid, sphingolipid, purines, thymine
Serine
533
This amino acid acts as a raw material in the biosynthesis of GABA
Glutamate
534
This amino acid acts as a raw material in the biosynthesis of creatine, polyamines, nitric oxide
Arginine
535
This amino acid acts as a raw material in the biosynthesis of serotonin, NAD+, NADP+, melatonin
Tryptophan
536
This amino acid acts as a raw material in the biosynthesis of catecholamines, thyroid hormones, melanin
Tyrosine
537
3 hormones dependent on tyrosine
Thyroid hormones
Melanin
Catecholamines
538
Deficiency of homogenistic acid oxidase in the degrative pathway of tyrosine which results in urine turning to black on standing with dark connective tissues (ochronosis)
Alkaptonuria
539
Congenital deficiency due tyrosinase deficieny or defective tyrosine transporters which leads to an increased risk for skin cancer.
Albinism
540
Autosomal recessive disorder that may either be due to decreased methionine, increased cysteine, B6, and folate or decreased affinity for cystathione synthase. This results in mental retardation, osteoporosis, tall stature, lens subluxation, and atherosclerosis.
Homocystinuria
541
What reaction measures total and direct bilirubin?
Van den bergs reaction
542
Examples of conjugated hyperbilirubinemia
Biliary tree obstruction
Dubin-Johnson syndrome
Rotor syndrome
543
Examples of unconjugated hyperbilirubinemia
```
Hemolytic anemia
Physiologic jaundice
Crigler-najjar syndrome types I and II
Gilbert syndrome
Toxic hyperbilirubinemia
```
544
Colors of biliverdin, bilirubin, urobilinogen, stercolin, urobilin
```
Biliverdin: green
Bilirubin: red orange
Urobilinogen: colorless
Stercolin: brown orange red
Urobilin: yellow
```
545
Summary of heme degradation
1. Formation of bilirubin
2. Uptake of bilirubin by the liver
3. Formation of bilirubin diglucoronide
4. Secretion of bilirubin into bile
5. Formation of urobilins in the intestine
546
Increase in MCHC is found in
Hereditary spherocytosis
547
Normoyctic normochromic anemia is found in
Anemia of chronic kidney disease
| Blood loss
548
Megaloblastic anemia is found in
Folate or B12 deficiency
| Pernicious anemia
549
Microcytic hypo chromic anemia is found in
IDA
Thalassemia
Lead poisoning
550
Poisoning due to this heavy metal leads to coar basophilic stippling of RBC, peripheral neuropathy, lines in gums, increas in urinary ALA and free erythrocytes porphorin
lead poisoning
551
Pyridoxine ficiency associated with isoniazid therapy results in this histopathologic finding
Sideroblastic anemia with ringed sideroblast
552
Which part of heme synthesis do these symptoms appear?
1. Photosensitivity
2. Neuropsychiatric symptoms
1. After ring formation
| 2. Before ring formation
553
Most common porphyria
Porphyria cutanea tarda
554
Where is B6 a cofactors of?
1. Heme synthesis
2. Synthesis of cystathionine from homocysteine
3. Transamination between alanine and a-ketoglutarate
555
Lead inhibits what two steps in heme synthesis?
1. Introduction of Fe 2+ into protoporphyrin IX via ferrochelatase
2. Condensation of two ALA molecules by zinc containing ALA dehydratase
556
Heme synthesis summary
1. Formation of ALA (via ALA synthase and B6)
2. Formation of porphobilinogen
3. Formation of uroporphyrinogen
4. Formation of heme
557
The initial and last three steps of heme synthesis occurs in?
The mitochondria
558
Common inherited defect of renal tubular amino acid transporter for its parent compound, Ornithine, Lysine, and arginine, in the PCT of the kidneys. It eventually precipitates and cause staghorn caliculi. What is its treatment?
Cystinuria is treated with acetazolamide to alkalinize the urine
559
What enzyme activates fatty acid for metabolism use?
Fatty-acyl-CoA synthetase
560
Cofactor required for fatty acid activation
Vitamin B5 or Panthotenic acid
561
Energy required to activate fatty acid
2 ATP
562
What is the product formed in fatty acid synthesis?
Palmitate (16:0)
563
Where does fatty acid synthesis occur?
Cytosol
Major: Liver and lactating mammary glands
Minor: adipose tissue
564
Substrates for fatty acid synthesis
1 acetyl CoA
7 malonyl CoA
NADPH
ATP
565
Rate limiting step in fatty acid synthesis
Acetyl CoA + ATP -> malonyl CoA
| Enzyme: acetyl CoA carboxylase
566
Steps in fatty acid synthesis
1. Synthesis of cytoplasmic acetyl CoA (transfer of mitochondrial acetyl CoA to cytoplasm via citrate shuttle)
2. Acetyl CoA carboxylation to malonyl CoA (via acetyl CoA carboxylase with biotin) [+ insulin, citrate]
3. Assembly of palmitate (via fatty acid synthase and Vit B5)
567
Steps in palmitate assembly
1. Condensation
2. Reduction
3. Dehydration
4. Reduction
568
What is the fate of Palmitate after its production?
1. Further elongation in SER and mitochondria
| 2. Desaturated in the ER (but not past the 9th carbon)
569
Main storage form of fatty acids
Triacylglycerols
570
Where does TAG synthesis occur?
Liver and adipose tissue
571
Sources of glycerol-3-phosphate
1. DHAP from glycolysis (liver and adipose)
| 2. Phosphorylation of free glycerol (liver)
572
What enzyme is responsible for the release of free fatty acids from TAGs?
Hormone sensitive lipases
573
In the bloodstream fatty acids are always bound to?
Albumin
574
Hormone sensitive lipases can only release what free fatty acids stored in TAG?
C1 & 3 thus resulting in
TAG -> 2 free FA and 2-mono acyl glycerol
575
Where does B-oxidation of fatty acids occur
Mitochondria of all cells, but the fatty acid activation raft occurs in the Cytosol
Exception: RBC, kidney medulla, neurons, testes
576
Rate limiting step in B-oxidation
Fatty acyl CoA + carnitine -> fatty acyl carnitine + CoA
| Enzyme: carnitine acyl transferase I
577
Cutoff number of carbons that do not need a shuttle
Less than 12 carbons
578
Steps in the carnitine shuttle
1. Fatty acyl synthase activates the fatty acid
2. Carnitine acyl transferase 1 attaches to fatty acyl to carnitine in the outer mitochondrial membrane
3. Fatty acyl-carnitine is shuttle through the inner membrane
4. Carnitine acyl transferase-2 transfers fatty acyl group back to a CoA in the mitochondrial matrix
579
Steps in beta oxidation
1. Oxidation
2. Hydratiion
3. Oxidation
4. Thiolysis
580
Beta oxidation of fatty acids with an odd number of carbon atoms releases?
Propionyl CoA which is converted to methylmalonyl coa (requires B12) then to succinyl CoA
581
Which is responsible for the conversion of very long chain fatty acids?
Peroxisomes but if unsaturated it requires 3,2 enol-CoA isomerase
582
Energy yield in ATP of beta oxidation of palmitate
129 ATP
7 NADH= 21
7 FAD= 14
8 acetyl CoA= 96
Activation = -2
583
Intake of this compound depletes the body's NAD+ supply leading to accumulation Of fat in the liver
Alcohol
584
Type of carnitine deficiency which leads to impaired FA oxidation and ketogenesis with hypoglycemia?
CPT-1 deficiency
585
Type of carnitine deficiency which affects skeletal muscle and when severe the liver
CPT-2 deficiency
586
It is a disorder school results in decreased fatty acid oxidation. Without the ATP to support gluconeogenesis, hypoglycemia becomes profound which may eventually leads to SIDS. It is prevented by frequent feeding with high carbohydrate and low fat diet.
Medium-chain fatty acyl-CoA dehydrogenase (MCAD) deficiency
587
Associated with eating unripe fruit of the akee tree which contains hypoglycin thus activating MC and SC acyl CoA dehydrogenase
Jamaican vomiting sickness
588
Rare neurological disorder which results to the accumulation of phytanic acid found in plant food stuff which blocks Boxidation
Refsum disease
589
Cerebrohepatorenal syndrome resulting from the absence of peroxisomes in all tissues, it is characterized by liver dysfunction, jaundice, MR, weakness, hypotonia, and craniofacial dimorphism
Zellweger syndrome
590
Defect in peroxismal activation of VLCFA thus leading to its accumulation. Ssx: apathy, behavral change, then visual loss spasticity, ataxia. All due to the fact since VLCFA are found in myelin tissue.
X-lied adrenoleukodystrophy
591
Where does ketogenesis occur?
Liver mitochondria
592
Products of ketogenesis
Acetoacetate and B-hydroxybutyrate (fuel)
| Acetone (cannot be used as fuel)
593
Rate limiting step of ketogenesis
Acetoacetyl CoA + acetyl CoA --(HMG CoA synthase)--> HMG CoA
594
What are the initial products that lead to the formation of acetyl CoA in ketogenolysis?
B-hydroxybutyrate -> acetoacetate -> acetyl coa
595
What peripheral tissues can oxidize ketone bodes?
Those with mitochondria like the renal cortex, brain, and skeletal muscle
596
Why cant liver convert acetoacetate to acetyl CoA?
It lacks succinyl-CoA acetoacetyl-CoA reductase (thiophorase)
597
What is the Urine test for ketones? What ketone type does not it detect?
Nitroprusside test
Does not detect b-hydroxybutyrate
598
Which part of cholesterol can a fatty acid attach to form a cholesteryl ester?
Single hydroxyl group of carbon 3 of the alpha ring
599
Where does cholesterol synthesis occur?
All cells in the Cytosol and SER majority of which are found in the liver and intestines
600
Substrates of cholesterol synthesis
Acetyl CoA, NADPH, ATP
601
Rate limiting step in cholesterol synthesis
HMG CoA --(HMG CoA reductase)--> mevalonate
602
Steps in Cholestid synthesis
1. Biosynthesis of mevalonate
2. Formation of isoprenoid units
3. Isoprene unit is formed from 6 isoprenoid units
4. Formation of lanosterol
5. Formation of cholesterol
603
How is the cholesterol ring eliminated?
Through conversion to bile salts then secretion to bile
604
Bile acid synthesis, found in the liver and Cytosol, rate limiting enzyme is?
Cholesterol-7-a-hydroxylase
605
What are the primary bile acids?
Cholic acid
| Chenocholic acid
606
What are the two amino acids used in bile acid conjugation to form bile salts?
Taurine and glycine
607
What are the secondary bile acids?
Deoxycholic acid
| Lithocholic acid
608
Where does steroid hormone synthesis occur?
SER of the adrenal glands, ovaries and testes, and placenta
609
What is blocked by the drug aminogluthetimide?
The conversion of cholesterol to pregnenolone by desmolase
610
The enzyme responsible for the breakdown of TAG to FA and:
A) 2-MAG from diet
B) FREE glycerol from chylomicrons and VLDL
C) 2-MAG from adipose
A) pancreatic lipase
B) Lipoprotein lipase
C) hormone sensitive lipase
611
Lipoprotein with the largest percentage of TG
Chylomicrons
612
Lipoprotein with the largest percentage of cholesteryl esters
LDL
613
Chylomicrons transport TG and cholesterol from where to where?
Intestines to tissues
614
VLDL transports TG from where to where?
Liver to tissues
615
What apoprotein activates lipoprotein lipase?
APO-CII
616
What apolipoprotein uptakes remnants by the liver?
APO E
617
Apolipoprotein B-48 is used by chylomicrons which are created by the?
Epithelial cells
618
What apolipoprotein is secreted by the liver for VDL?
B-100
619
How does IDL become LDL?
By picking up cholesterol from HD!
620
Which apoprotein delivers cholesterol into cells?
LDL
621
Which apolipoprotein is used by HDL to activate lecithin cholesterol acyl transferase or LCAT to produce cholesterol esters?
APO-A1
622
Difference between Type II familial hypercholesterolemia and type IV familial hypertriglyceredemia?
The former has high LDL leader to xanthomas and xanthelasmas with increased risk of atherosclerosis and CHD
The latter has increased VLDL production leading to a triad of
1. DM type 2
2. CAD
3. Obesity
623
Phospholipid is composed of
DAG
Alcohol
Phosphodiester bond
624
Most abundant phospholipid which is important in nervous transmission
Phosphatidylcholine
625
Phospholipid playing a role in apoptosis
Phosphatidyl serine
626
Phospholipid that is a major component of surfactant?
Dipalmitoylphosphatidylcholine
627
Phospholipid reservoir for arachidonic acid in the membranes
Phosphatidylinositol
628
What phospholipid is essential in mitochondrial function which is also used as a non-troponemal test due to its ability to act as an antigen?
Cardiolipin
629
```
Composition of these glycolipids:
Ceramide
Cerebroside
Globoside
Ganglioside
Sulfatide
```
Ceramide: sphingosine + FA
```
Ceramide + ________
Glucose or galactose = Cerebroside
Oligosacchardide = Globoside
N-acetylneuramic acid = Ganglioside
Sulfated galactose = Sulfatide
```
630
Hexosaminidase a ficiency leading to Ssx like cherry red macula, MR, hypotonia
Tay-Sachs disease
631
A-galactosidase deficiency leading to 3Rs: recessive x-linked, rash, renal failure
Fabrys disease
632
B-glucosidase deficiency leading to hepatosplenomegaly and erosion of long bones
Gauchers dissease
633
Sphingomyelinase deficiency leading to hepatosplenomegaly
Nieman-pick disease
634
The set of all proteins expressed by an individual at a particular time
Proteome
635
Aims to identify the entire complement of proteins elaborated by a cell under diverse conditions
Proteomics
636
What amino acid is needed to form ALA in heme synthesis?
Glycine combined with succinyl CoA
637
Which amino acid carries nitrogen from the liver?
Alanine
638
Which amino acids are implicated in maple syrup disease
valine, lucine, isoleucine
639
What enzyme is responsible for the buildup of phenyl lactate, phenyl acetate, and phenylpyruvate?
Phenylalanine hydroxylase
640
What amino acid is the precursor for niacin, serotonin, and melatonin?
Serotonin
641
What is the amino acid precursor for homocysteine?
Methionine
642
What amino acid contributes to the fibrous structure of collagen and interrupts a-helices in globular proteins?
Proline
643
Increase of the combination of this Amino acid is responsible for the curly hair of people?
Cysteine + cysteine = cystine
644
Amino acids with sites for O-linked glycosylation in the Golgi apparatus?
Serine and threonine
645
Site for n-linked glycosylation in the ER
Asparagine
646
Amino acid deaminated by an enzyme which results in the formation of ammonia. This is the major carrier of nitrogen to the liver from peripheral tissues,
Glutaminase deaminates glutamine
647
Amino acid used in the determination for Folic acid deficiency. What is the test called?
Histidine used in the N-forminoglutamate excretion test
| Increased amounts of FIGu in urine by Folic acid deficient individuals after histindine intake
648
Precursor amino acid for creatinine, urea, nitric oxide
Arginine
649
Essential amino acids that cannot be synthesized by the body and must come from the diet
PVT TIM HALL always ARGues and never TYRes
Phenylalanine, valine, tryptophan, threonine' isoleucine, methionine, histidine, argenine, Leucine, Lysine
650
Heme is a complex of?
Protoporphorin IX and heme
651
What is the Bohr effect?
HBO2 + H+ HbH + O2
652
What is an oxidized for of HB (Fe 3+) that does not bind O2 readily which could lead to chocolate cyanosis ? It is treated with oral methylene blue or ascorbic acid up to IV methylene blue.
Methemoglobin
653
Hemoglobin bound to carbon monoxide instead of O2 leading to a cherry pink color.
Carboxyhemoglobin
654
HB bound to carbon dioxide is called
Carbaminohenoglobin
655
Classification of alpha and beta thalassemia
Alpha: silent carrier, a-thalassemia trait, Hb H disease, hydrops fetalis
Beta: B-thalassemia minor and major
656
Most frequently affected collagen in Ehler Danlos syndrome leading to hyper extensible skin, tendency to bleed, hyper mobile joints, and increased risk for berry aneurysms.
Collagen type 3
657
Collagen I mutation leading to bendable and easily fractured bones. Accompanied with blue sclerae, hearing loss, and dental imperfections.
Osteogenesis imperfecta
658
Vitamin C deficiency leading to decreased hydroxylation of collagen. This leads to sore spongy gums, loose teeth, poor wound healing, and petecchiae on skin and mucous membranes.
Scurvy
659
Type IV collagen defect leading to hematuria and ESRD
Alpert syndrome
660
Collagen defect leading to kinky hair due to a deficiency of copper required by lysyl oxidase to strengthen collagen fibers.
Menke syndrome
661
Skin breaking and blisters as a result for minor trauma. This disease is due to a defect in collage VII.
Epidermolysis bullosa
662
Like collagen elastin has pro line and Lysine but has little and no?
Hydroxyproline
| Hydroxylysine
663
Protein degradation mechanisms of nitrogen
Energy dependent ubiquitin-proteosome mechanism
| Non-energy dependent degradation enzyme
664
Phases in amino acid catabolism
First phase: removal of a-amino group forming ammonia and a corresponding ketoacid
Second phase: carbon skeletons of a-ketoacids are converted to common intermediates of energy producing metabolic pathwas
665
Two main steps in nitrogen removal from AA
1. Transamination
| 2. Oxidative deamination
666
Where does transamination occur?
All cells of the body
667
All but two amino acids transfer their amino groups to a-ketoglutarate except?
Lysine and threonine
668
What is the coenzyme for the two aminotransferases?
Pyridoxal phosphate (vitamin B6)
669
Oxidative deamination occurs where and for which amino acid only?
Liver and kidney
| Only glutamate
670
Glutamate is oxidized by glutamate dehydrogenases and deaminated to form ?
free ammonia which is used to make urea
671
What does the conversion of glutamate to a-ketoglutarate yield? What about vice versa?
Glutamate -> a ketoglutarate NH3 + NADH
| A ketoglutarate -> glutamate NADP+ + NH3
672
How is excess nitrogen removal from peripheral tissues removed?
1. Glutamine: via glutamate + ammonia (through Flutamide synthaetase)
2. Alanine: via glucose -> pyruvate + glutamate -> alanine cycle
673
Glutaminase deaminates glutamine to produce ammonium ion which is excreted from the body. Where are the two tissues this enzyme could be located?
Kidneys and small intestines
674
Another name for urea cycle
Ornithine cycle or krebs-henseleit cycle
675
What are the donors of the urea molecule?
1. NH3 from free ammonia
2. NH3 from aspartate
3. 1C and 1O from CO2
676
Reactions in the urea cycle
1. Formation of carbamoyl phosphate (via carbamoyl phosphate synthetase I)
2. Formation of citrulline (via Ornithine transcarbamoylase)
3. Synthesis of arginosuccinate (arginosuccinate synthetase)
4. Cleavage of arginosuccinate to form arginine (Arginosuccinase)
5. Arginine cleavage to yield urea and Ornithine (arginase)
677
Rate limiting step of urea cycle
Carbamoyl phosphate synthetase I
678
Energy requirement of urea cycle
4 ATP
679
Co factors of urea cycle
N-acetylglutamate
| Biotin
680
Hereditary hyperammonemia produces symptoms such as
Hyperammonemia, elevated blood glutamine, decreased BUN
| Parents with lethargy, vomiting, hyperventilation, convulsions, cerebral edema, coma, and death
681
Treatment for hereditary hyperammonemia
Low protein diet
| Administration of sodium benzoate or phenylpyruvate to capture and excrete excess nitrogen
682
Ketogenic carbon skeletons of AA
Leucine
Lysine
Yields acetoacetate or acetyl-coa/ acetoacetyl-coa
683
Ketogenic and glucogenic carbon skeletons of AA
```
WIFY
Phenylalanine
Isoleucine
Tryptophan
Tyrosine
```
Yields Ketogenic and glucose or glycogen by products
684
This amino acid acts as a raw material in the biosynthesis of Heme, purines, creatine
Glycine
685
This amino acid acts as a raw material in the biosynthesis of phospholipid, sphingolipid, purines, thymine
Serine
686
This amino acid acts as a raw material in the biosynthesis of GABA
Glutamate
687
This amino acid acts as a raw material in the biosynthesis of creatine, polyamines, nitric oxide
Arginine
688
This amino acid acts as a raw material in the biosynthesis of serotonin, NAD+, NADP+, melatonin
Tryptophan
689
This amino acid acts as a raw material in the biosynthesis of catecholamines, thyroid hormones, melanin
Tyrosine
690
3 hormones dependent on tyrosine
Thyroid hormones
Melanin
Catecholamines
691
Deficiency of homogenistic acid oxidase in the degrative pathway of tyrosine which results in urine turning to black on standing with dark connective tissues (ochronosis)
Alkaptonuria
692
Congenital deficiency due tyrosinase deficieny or defective tyrosine transporters which leads to an increased risk for skin cancer.
Albinism
693
Autosomal recessive disorder that may either be due to decreased methionine, increased cysteine, B6, and folate or decreased affinity for cystathione synthase. This results in mental retardation, osteoporosis, tall stature, lens subluxation, and atherosclerosis.
Homocystinuria
694
Common inherited defect of renal tubular amino acid transporter for its parent compound, Ornithine, Lysine, and arginine, in the PCT of the kidneys. It eventually precipitates and cause staghorn caliculi. What is its treatment?
Cystinuria is treated with acetazolamide to alkalinize the urine
695
The initial and last three steps of heme synthesis occurs in?
The mitochondria
696
Heme synthesis summary
1. Formation of ALA (via ALA synthase and B6)
2. Formation of porphobilinogen
3. Formation of uroporphyrinogen
4. Formation of heme
697
Lead inhibits what two steps in heme synthesis?
1. Introduction of Fe 2+ into protoporphyrin IX via ferrochelatase
2. Condensation of two ALA molecules by zinc containing ALA dehydratase
698
Where is B6 a cofactors of?
1. Heme synthesis
2. Synthesis of cystathionine from homocysteine
3. Transamination between alanine and a-ketoglutarate
699
Most common porphyria
Porphyria cutanea tarda
700
Which part of heme synthesis do these symptoms appear?
1. Photosensitivity
2. Neuropsychiatric symptoms
1. After ring formation
| 2. Before ring formation
701
Pyridoxine ficiency associated with isoniazid therapy results in this histopathologic finding
Sideroblastic anemia with ringed sideroblast
702
Poisoning due to this heavy metal leads to coar basophilic stippling of RBC, peripheral neuropathy, lines in gums, increas in urinary ALA and free erythrocytes porphorin
lead poisoning
703
Microcytic hypo chromic anemia is found in
IDA
Thalassemia
Lead poisoning
704
Megaloblastic anemia is found in
Folate or B12 deficiency
| Pernicious anemia
705
Normoyctic normochromic anemia is found in
Anemia of chronic kidney disease
| Blood loss
706
Increase in MCHC is found in
Hereditary spherocytosis
707
Summary of heme degradation
1. Formation of bilirubin
2. Uptake of bilirubin by the liver
3. Formation of bilirubin diglucoronide
4. Secretion of bilirubin into bile
5. Formation of urobilins in the intestine
708
Colors of biliverdin, bilirubin, urobilinogen, stercolin, urobilin
```
Biliverdin: green
Bilirubin: red orange
Urobilinogen: colorless
Stercolin: brown orange red
Urobilin: yellow
```
709
Examples of unconjugated hyperbilirubinemia
```
Hemolytic anemia
Physiologic jaundice
Crigler-najjar syndrome types I and II
Gilbert syndrome
Toxic hyperbilirubinemia
```
710
Examples of conjugated hyperbilirubinemia
Biliary tree obstruction
Dubin-Johnson syndrome
Rotor syndrome
711
What reaction measures total and direct bilirubin?
Van den bergs reaction
712
What enzyme activates fatty acid for metabolism use?
Fatty-acyl-CoA synthetase
713
Cofactor required for fatty acid activation
Vitamin B5 or Panthotenic acid
714
Energy required to activate fatty acid
2 ATP
715
What is the product formed in fatty acid synthesis?
Palmitate (16:0)
716
Where does fatty acid synthesis occur?
Cytosol
Major: Liver and lactating mammary glands
Minor: adipose tissue
717
Substrates for fatty acid synthesis
1 acetyl CoA
7 malonyl CoA
NADPH
ATP
718
Rate limiting step in fatty acid synthesis
Acetyl CoA + ATP -> malonyl CoA
| Enzyme: acetyl CoA carboxylase
719
Steps in fatty acid synthesis
1. Synthesis of cytoplasmic acetyl CoA (transfer of mitochondrial acetyl CoA to cytoplasm via citrate shuttle)
2. Acetyl CoA carboxylation to malonyl CoA (via acetyl CoA carboxylase with biotin) [+ insulin, citrate]
3. Assembly of palmitate (via fatty acid synthase and Vit B5)
720
Steps in palmitate assembly
1. Condensation
2. Reduction
3. Dehydration
4. Reduction
721
What is the fate of Palmitate after its production?
1. Further elongation in SER and mitochondria
| 2. Desaturated in the ER (but not past the 9th carbon)
722
Main storage form of fatty acids
Triacylglycerols
723
Where does TAG synthesis occur?
Liver and adipose tissue
724
Sources of glycerol-3-phosphate
1. DHAP from glycolysis (liver and adipose)
| 2. Phosphorylation of free glycerol (liver)
725
What enzyme is responsible for the release of free fatty acids from TAGs?
Hormone sensitive lipases
726
In the bloodstream fatty acids are always bound to?
Albumin
727
Hormone sensitive lipases can only release what free fatty acids stored in TAG?
C1 & 3 thus resulting in
TAG -> 2 free FA and 2-mono acyl glycerol
728
Where does B-oxidation of fatty acids occur
Mitochondria of all cells, but the fatty acid activation raft occurs in the Cytosol
Exception: RBC, kidney medulla, neurons, testes
729
Rate limiting step in B-oxidation
Fatty acyl CoA + carnitine -> fatty acyl carnitine + CoA
| Enzyme: carnitine acyl transferase I
730
Cutoff number of carbons that do not need a shuttle
Less than 12 carbons
731
Steps in the carnitine shuttle
1. Fatty acyl synthase activates the fatty acid
2. Carnitine acyl transferase 1 attaches to fatty acyl to carnitine in the outer mitochondrial membrane
3. Fatty acyl-carnitine is shuttle through the inner membrane
4. Carnitine acyl transferase-2 transfers fatty acyl group back to a CoA in the mitochondrial matrix
732
Steps in beta oxidation
1. Oxidation
2. Hydratiion
3. Oxidation
4. Thiolysis
733
Beta oxidation of fatty acids with an odd number of carbon atoms releases?
Propionyl CoA which is converted to methylmalonyl coa (requires B12) then to succinyl CoA
734
Which is responsible for the conversion of very long chain fatty acids?
Peroxisomes but if unsaturated it requires 3,2 enol-CoA isomerase
735
Energy yield in ATP of beta oxidation of palmitate
129 ATP
7 NADH= 21
7 FAD= 14
8 acetyl CoA= 96
Activation = -2
736
Intake of this compound depletes the body's NAD+ supply leading to accumulation Of fat in the liver
Alcohol
737
Type of carnitine deficiency which leads to impaired FA oxidation and ketogenesis with hypoglycemia?
CPT-1 deficiency
738
Type of carnitine deficiency which affects skeletal muscle and when severe the liver
CPT-2 deficiency
739
It is a disorder school results in decreased fatty acid oxidation. Without the ATP to support gluconeogenesis, hypoglycemia becomes profound which may eventually leads to SIDS. It is prevented by frequent feeding with high carbohydrate and low fat diet.
Medium-chain fatty acyl-CoA dehydrogenase (MCAD) deficiency
740
Associated with eating unripe fruit of the akee tree which contains hypoglycin thus activating MC and SC acyl CoA dehydrogenase
Jamaican vomiting sickness
741
Rare neurological disorder which results to the accumulation of phytanic acid found in plant food stuff which blocks Boxidation
Refsum disease
742
Cerebrohepatorenal syndrome resulting from the absence of peroxisomes in all tissues, it is characterized by liver dysfunction, jaundice, MR, weakness, hypotonia, and craniofacial dimorphism
Zellweger syndrome
743
Defect in peroxismal activation of VLCFA thus leading to its accumulation. Ssx: apathy, behavral change, then visual loss spasticity, ataxia. All due to the fact since VLCFA are found in myelin tissue.
X-lied adrenoleukodystrophy
744
Where does ketogenesis occur?
Liver mitochondria
745
Products of ketogenesis
Acetoacetate and B-hydroxybutyrate (fuel)
| Acetone (cannot be used as fuel)
746
Rate limiting step of ketogenesis
Acetoacetyl CoA + acetyl CoA --(HMG CoA synthase)--> HMG CoA
747
What are the initial products that lead to the formation of acetyl CoA in ketogenolysis?
B-hydroxybutyrate -> acetoacetate -> acetyl coa
748
What peripheral tissues can oxidize ketone bodes?
Those with mitochondria like the renal cortex, brain, and skeletal muscle
749
Why cant liver convert acetoacetate to acetyl CoA?
It lacks succinyl-CoA acetoacetyl-CoA reductase (thiophorase)
750
What is the Urine test for ketones? What ketone type does not it detect?
Nitroprusside test
Does not detect b-hydroxybutyrate
751
Which part of cholesterol can a fatty acid attach to form a cholesteryl ester?
Single hydroxyl group of carbon 3 of the alpha ring
752
Where does cholesterol synthesis occur?
All cells in the Cytosol and SER majority of which are found in the liver and intestines
753
Substrates of cholesterol synthesis
Acetyl CoA, NADPH, ATP
754
Rate limiting step in cholesterol synthesis
HMG CoA --(HMG CoA reductase)--> mevalonate
755
Steps in Cholestid synthesis
1. Biosynthesis of mevalonate
2. Formation of isoprenoid units
3. Isoprene unit is formed from 6 isoprenoid units
4. Formation of lanosterol
5. Formation of cholesterol
756
How is the cholesterol ring eliminated?
Through conversion to bile salts then secretion to bile
757
Bile acid synthesis, found in the liver and Cytosol, rate limiting enzyme is?
Cholesterol-7-a-hydroxylase
758
What are the primary bile acids?
Cholic acid
| Chenocholic acid
759
What are the two amino acids used in bile acid conjugation to form bile salts?
Taurine and glycine
760
What are the secondary bile acids?
Deoxycholic acid
| Lithocholic acid
761
Where does steroid hormone synthesis occur?
SER of the adrenal glands, ovaries and testes, and placenta
762
What is blocked by the drug aminogluthetimide?
The conversion of cholesterol to pregnenolone by desmolase
763
The enzyme responsible for the breakdown of TAG to FA and:
A) 2-MAG from diet
B) FREE glycerol from chylomicrons and VLDL
C) 2-MAG from adipose
A) pancreatic lipase
B) Lipoprotein lipase
C) hormone sensitive lipase
764
Lipoprotein with the largest percentage of TG
Chylomicrons
765
Lipoprotein with the largest percentage of cholesteryl esters
LDL
766
Chylomicrons transport TG and cholesterol from where to where?
Intestines to tissues
767
VLDL transports TG from where to where?
Liver to tissues
768
What apoprotein activates lipoprotein lipase?
APO-CII
769
What apolipoprotein uptakes remnants by the liver?
APO E
770
Apolipoprotein B-48 is used by chylomicrons which are created by the?
Epithelial cells
771
What apolipoprotein is secreted by the liver for VDL?
B-100
772
How does IDL become LDL?
By picking up cholesterol from HD!
773
Which apoprotein delivers cholesterol into cells?
LDL
774
Which apolipoprotein is used by HDL to activate lecithin cholesterol acyl transferase or LCAT to produce cholesterol esters?
APO-A1
775
Difference between Type II familial hypercholesterolemia and type IV familial hypertriglyceredemia?
The former has high LDL leader to xanthomas and xanthelasmas with increased risk of atherosclerosis and CHD
The latter has increased VLDL production leading to a triad of
1. DM type 2
2. CAD
3. Obesity
776
Phospholipid is composed of
DAG
Alcohol
Phosphodiester bond
777
Most abundant phospholipid which is important in nervous transmission
Phosphatidylcholine
778
Phospholipid playing a role in apoptosis
Phosphatidyl serine
779
Phospholipid that is a major component of surfactant?
Dipalmitoylphosphatidylcholine
780
Phospholipid reservoir for arachidonic acid in the membranes
Phosphatidylinositol
781
What phospholipid is essential in mitochondrial function which is also used as a non-troponemal test due to its ability to act as an antigen?
Cardiolipin
782
```
Composition of these glycolipids:
Ceramide
Cerebroside
Globoside
Ganglioside
Sulfatide
```
Ceramide: sphingosine + FA
```
Ceramide + ________
Glucose or galactose = Cerebroside
Oligosacchardide = Globoside
N-acetylneuramic acid = Ganglioside
Sulfated galactose = Sulfatide
```
783
Hexosaminidase a ficiency leading to Ssx like cherry red macula, MR, hypotonia
Tay-Sachs disease
784
A-galactosidase deficiency leading to 3Rs: recessive x-linked, rash, renal failure
Fabrys disease
785
B-glucosidase deficiency leading to hepatosplenomegaly and erosion of long bones
Gauchers dissease
786
Sphingomyelinase deficiency leading to hepatosplenomegaly
Nieman-pick disease
787
The set of all proteins expressed by an individual at a particular time
Proteome
788
Aims to identify the entire complement of proteins elaborated by a cell under diverse conditions
Proteomics
789
What amino acid is needed to form ALA in heme synthesis?
Glycine combined with succinyl CoA
790
Which amino acid carries nitrogen from the liver?
Alanine
791
Which amino acids are implicated in maple syrup disease
valine, lucine, isoleucine
792
What enzyme is responsible for the buildup of phenyl lactate, phenyl acetate, and phenylpyruvate?
Phenylalanine hydroxylase
793
What amino acid is the precursor for niacin, serotonin, and melatonin?
Serotonin
794
What is the amino acid precursor for homocysteine?
Methionine
795
What amino acid contributes to the fibrous structure of collagen and interrupts a-helices in globular proteins?
Proline
796
Increase of the combination of this Amino acid is responsible for the curly hair of people?
Cysteine + cysteine = cystine
797
Amino acids with sites for O-linked glycosylation in the Golgi apparatus?
Serine and threonine
798
Site for n-linked glycosylation in the ER
Asparagine
799
Amino acid deaminated by an enzyme which results in the formation of ammonia. This is the major carrier of nitrogen to the liver from peripheral tissues,
Glutaminase deaminates glutamine
800
Amino acid used in the determination for Folic acid deficiency. What is the test called?
Histidine used in the N-forminoglutamate excretion test
| Increased amounts of FIGu in urine by Folic acid deficient individuals after histindine intake
801
Precursor amino acid for creatinine, urea, nitric oxide
Arginine
802
Essential amino acids that cannot be synthesized by the body and must come from the diet
PVT TIM HALL always ARGues and never TYRes
Phenylalanine, valine, tryptophan, threonine' isoleucine, methionine, histidine, argenine, Leucine, Lysine
803
Heme is a complex of?
Protoporphorin IX and heme
804
What is the Bohr effect?
HBO2 + H+ HbH + O2
805
What is an oxidized for of HB (Fe 3+) that does not bind O2 readily which could lead to chocolate cyanosis ? It is treated with oral methylene blue or ascorbic acid up to IV methylene blue.
Methemoglobin
806
Hemoglobin bound to carbon monoxide instead of O2 leading to a cherry pink color.
Carboxyhemoglobin
807
HB bound to carbon dioxide is called
Carbaminohenoglobin
808
Classification of alpha and beta thalassemia
Alpha: silent carrier, a-thalassemia trait, Hb H disease, hydrops fetalis
Beta: B-thalassemia minor and major
809
Most frequently affected collagen in Ehler Danlos syndrome leading to hyper extensible skin, tendency to bleed, hyper mobile joints, and increased risk for berry aneurysms.
Collagen type 3
810
Collagen I mutation leading to bendable and easily fractured bones. Accompanied with blue sclerae, hearing loss, and dental imperfections.
Osteogenesis imperfecta
811
Vitamin C deficiency leading to decreased hydroxylation of collagen. This leads to sore spongy gums, loose teeth, poor wound healing, and petecchiae on skin and mucous membranes.
Scurvy
812
Type IV collagen defect leading to hematuria and ESRD
Alpert syndrome
813
Collagen defect leading to kinky hair due to a deficiency of copper required by lysyl oxidase to strengthen collagen fibers.
Menke syndrome
814
Skin breaking and blisters as a result for minor trauma. This disease is due to a defect in collage VII.
Epidermolysis bullosa
815
Like collagen elastin has pro line and Lysine but has little and no?
Hydroxyproline
| Hydroxylysine
816
Protein degradation mechanisms of nitrogen
Energy dependent ubiquitin-proteosome mechanism
| Non-energy dependent degradation enzyme
817
Phases in amino acid catabolism
First phase: removal of a-amino group forming ammonia and a corresponding ketoacid
Second phase: carbon skeletons of a-ketoacids are converted to common intermediates of energy producing metabolic pathwas
818
Two main steps in nitrogen removal from AA
1. Transamination
| 2. Oxidative deamination
819
Where does transamination occur?
All cells of the body
820
All but two amino acids transfer their amino groups to a-ketoglutarate except?
Lysine and threonine
821
What is the coenzyme for the two aminotransferases?
Pyridoxal phosphate (vitamin B6)
822
Oxidative deamination occurs where and for which amino acid only?
Liver and kidney
| Only glutamate
823
Glutamate is oxidized by glutamate dehydrogenases and deaminated to form ?
free ammonia which is used to make urea
824
What does the conversion of glutamate to a-ketoglutarate yield? What about vice versa?
Glutamate -> a ketoglutarate NH3 + NADH
| A ketoglutarate -> glutamate NADP+ + NH3
825
How is excess nitrogen removal from peripheral tissues removed?
1. Glutamine: via glutamate + ammonia (through Flutamide synthaetase)
2. Alanine: via glucose -> pyruvate + glutamate -> alanine cycle
826
Glutaminase deaminates glutamine to produce ammonium ion which is excreted from the body. Where are the two tissues this enzyme could be located?
Kidneys and small intestines
827
Another name for urea cycle
Ornithine cycle or krebs-henseleit cycle
828
What are the donors of the urea molecule?
1. NH3 from free ammonia
2. NH3 from aspartate
3. 1C and 1O from CO2
829
Reactions in the urea cycle
1. Formation of carbamoyl phosphate (via carbamoyl phosphate synthetase I)
2. Formation of citrulline (via Ornithine transcarbamoylase)
3. Synthesis of arginosuccinate (arginosuccinate synthetase)
4. Cleavage of arginosuccinate to form arginine (Arginosuccinase)
5. Arginine cleavage to yield urea and Ornithine (arginase)
830
Rate limiting step of urea cycle
Carbamoyl phosphate synthetase I
831
Energy requirement of urea cycle
4 ATP
832
Co factors of urea cycle
N-acetylglutamate
| Biotin
833
Hereditary hyperammonemia produces symptoms such as
Hyperammonemia, elevated blood glutamine, decreased BUN
| Parents with lethargy, vomiting, hyperventilation, convulsions, cerebral edema, coma, and death
834
Treatment for hereditary hyperammonemia
Low protein diet
| Administration of sodium benzoate or phenylpyruvate to capture and excrete excess nitrogen
835
Ketogenic carbon skeletons of AA
Leucine
Lysine
Yields acetoacetate or acetyl-coa/ acetoacetyl-coa
836
Ketogenic and glucogenic carbon skeletons of AA
```
WIFY
Phenylalanine
Isoleucine
Tryptophan
Tyrosine
```
Yields Ketogenic and glucose or glycogen by products
837
This amino acid acts as a raw material in the biosynthesis of Heme, purines, creatine
Glycine
838
This amino acid acts as a raw material in the biosynthesis of phospholipid, sphingolipid, purines, thymine
Serine
839
This amino acid acts as a raw material in the biosynthesis of GABA
Glutamate
840
This amino acid acts as a raw material in the biosynthesis of creatine, polyamines, nitric oxide
Arginine
841
This amino acid acts as a raw material in the biosynthesis of serotonin, NAD+, NADP+, melatonin
Tryptophan
842
This amino acid acts as a raw material in the biosynthesis of catecholamines, thyroid hormones, melanin
Tyrosine
843
3 hormones dependent on tyrosine
Thyroid hormones
Melanin
Catecholamines
844
Deficiency of homogenistic acid oxidase in the degrative pathway of tyrosine which results in urine turning to black on standing with dark connective tissues (ochronosis)
Alkaptonuria
845
Congenital deficiency due tyrosinase deficieny or defective tyrosine transporters which leads to an increased risk for skin cancer.
Albinism
846
Autosomal recessive disorder that may either be due to decreased methionine, increased cysteine, B6, and folate or decreased affinity for cystathione synthase. This results in mental retardation, osteoporosis, tall stature, lens subluxation, and atherosclerosis.
Homocystinuria
847
Common inherited defect of renal tubular amino acid transporter for its parent compound, Ornithine, Lysine, and arginine, in the PCT of the kidneys. It eventually precipitates and cause staghorn caliculi. What is its treatment?
Cystinuria is treated with acetazolamide to alkalinize the urine
848
The initial and last three steps of heme synthesis occurs in?
The mitochondria
849
Heme synthesis summary
1. Formation of ALA (via ALA synthase and B6)
2. Formation of porphobilinogen
3. Formation of uroporphyrinogen
4. Formation of heme
850
Lead inhibits what two steps in heme synthesis?
1. Introduction of Fe 2+ into protoporphyrin IX via ferrochelatase
2. Condensation of two ALA molecules by zinc containing ALA dehydratase
851
Where is B6 a cofactors of?
1. Heme synthesis
2. Synthesis of cystathionine from homocysteine
3. Transamination between alanine and a-ketoglutarate
852
Most common porphyria
Porphyria cutanea tarda
853
Which part of heme synthesis do these symptoms appear?
1. Photosensitivity
2. Neuropsychiatric symptoms
1. After ring formation
| 2. Before ring formation
854
Pyridoxine ficiency associated with isoniazid therapy results in this histopathologic finding
Sideroblastic anemia with ringed sideroblast
855
Poisoning due to this heavy metal leads to coar basophilic stippling of RBC, peripheral neuropathy, lines in gums, increas in urinary ALA and free erythrocytes porphorin
lead poisoning
856
Microcytic hypo chromic anemia is found in
IDA
Thalassemia
Lead poisoning
857
Megaloblastic anemia is found in
Folate or B12 deficiency
| Pernicious anemia
858
Normoyctic normochromic anemia is found in
Anemia of chronic kidney disease
| Blood loss
859
Increase in MCHC is found in
Hereditary spherocytosis
860
Summary of heme degradation
1. Formation of bilirubin
2. Uptake of bilirubin by the liver
3. Formation of bilirubin diglucoronide
4. Secretion of bilirubin into bile
5. Formation of urobilins in the intestine
861
Colors of biliverdin, bilirubin, urobilinogen, stercolin, urobilin
```
Biliverdin: green
Bilirubin: red orange
Urobilinogen: colorless
Stercolin: brown orange red
Urobilin: yellow
```
862
Examples of unconjugated hyperbilirubinemia
```
Hemolytic anemia
Physiologic jaundice
Crigler-najjar syndrome types I and II
Gilbert syndrome
Toxic hyperbilirubinemia
```
863
What reaction measures total and direct bilirubin?
Van den bergs reaction
864
Examples of conjugated hyperbilirubinemia
Biliary tree obstruction
Dubin-Johnson syndrome
Rotor syndrome
865
What enzyme activates fatty acid for metabolism use?
Fatty-acyl-CoA synthetase
866
Cofactor required for fatty acid activation
Vitamin B5 or Panthotenic acid
867
Energy required to activate fatty acid
2 ATP
868
What is the product formed in fatty acid synthesis?
Palmitate (16:0)
869
Where does fatty acid synthesis occur?
Cytosol
Major: Liver and lactating mammary glands
Minor: adipose tissue
870
Substrates for fatty acid synthesis
1 acetyl CoA
7 malonyl CoA
NADPH
ATP
871
Rate limiting step in fatty acid synthesis
Acetyl CoA + ATP -> malonyl CoA
| Enzyme: acetyl CoA carboxylase
872
Steps in fatty acid synthesis
1. Synthesis of cytoplasmic acetyl CoA (transfer of mitochondrial acetyl CoA to cytoplasm via citrate shuttle)
2. Acetyl CoA carboxylation to malonyl CoA (via acetyl CoA carboxylase with biotin) [+ insulin, citrate]
3. Assembly of palmitate (via fatty acid synthase and Vit B5)
873
Steps in palmitate assembly
1. Condensation
2. Reduction
3. Dehydration
4. Reduction
874
What is the fate of Palmitate after its production?
1. Further elongation in SER and mitochondria
| 2. Desaturated in the ER (but not past the 9th carbon)
875
Main storage form of fatty acids
Triacylglycerols
876
Where does TAG synthesis occur?
Liver and adipose tissue
877
Sources of glycerol-3-phosphate
1. DHAP from glycolysis (liver and adipose)
| 2. Phosphorylation of free glycerol (liver)
878
What enzyme is responsible for the release of free fatty acids from TAGs?
Hormone sensitive lipases
879
In the bloodstream fatty acids are always bound to?
Albumin
880
Hormone sensitive lipases can only release what free fatty acids stored in TAG?
C1 & 3 thus resulting in
TAG -> 2 free FA and 2-mono acyl glycerol
881
Where does B-oxidation of fatty acids occur
Mitochondria of all cells, but the fatty acid activation raft occurs in the Cytosol
Exception: RBC, kidney medulla, neurons, testes
882
Rate limiting step in B-oxidation
Fatty acyl CoA + carnitine -> fatty acyl carnitine + CoA
| Enzyme: carnitine acyl transferase I
883
Cutoff number of carbons that do not need a shuttle
Less than 12 carbons
884
Steps in the carnitine shuttle
1. Fatty acyl synthase activates the fatty acid
2. Carnitine acyl transferase 1 attaches to fatty acyl to carnitine in the outer mitochondrial membrane
3. Fatty acyl-carnitine is shuttle through the inner membrane
4. Carnitine acyl transferase-2 transfers fatty acyl group back to a CoA in the mitochondrial matrix
885
Steps in beta oxidation
1. Oxidation
2. Hydratiion
3. Oxidation
4. Thiolysis
886
Beta oxidation of fatty acids with an odd number of carbon atoms releases?
Propionyl CoA which is converted to methylmalonyl coa (requires B12) then to succinyl CoA
887
Which is responsible for the conversion of very long chain fatty acids?
Peroxisomes but if unsaturated it requires 3,2 enol-CoA isomerase
888
Energy yield in ATP of beta oxidation of palmitate
129 ATP
7 NADH= 21
7 FAD= 14
8 acetyl CoA= 96
Activation = -2
889
Intake of this compound depletes the body's NAD+ supply leading to accumulation Of fat in the liver
Alcohol
890
Type of carnitine deficiency which leads to impaired FA oxidation and ketogenesis with hypoglycemia?
CPT-1 deficiency
891
Type of carnitine deficiency which affects skeletal muscle and when severe the liver
CPT-2 deficiency
892
It is a disorder school results in decreased fatty acid oxidation. Without the ATP to support gluconeogenesis, hypoglycemia becomes profound which may eventually leads to SIDS. It is prevented by frequent feeding with high carbohydrate and low fat diet.
Medium-chain fatty acyl-CoA dehydrogenase (MCAD) deficiency
893
Associated with eating unripe fruit of the akee tree which contains hypoglycin thus activating MC and SC acyl CoA dehydrogenase
Jamaican vomiting sickness
894
Rare neurological disorder which results to the accumulation of phytanic acid found in plant food stuff which blocks Boxidation
Refsum disease
895
Cerebrohepatorenal syndrome resulting from the absence of peroxisomes in all tissues, it is characterized by liver dysfunction, jaundice, MR, weakness, hypotonia, and craniofacial dimorphism
Zellweger syndrome
896
Defect in peroxismal activation of VLCFA thus leading to its accumulation. Ssx: apathy, behavral change, then visual loss spasticity, ataxia. All due to the fact since VLCFA are found in myelin tissue.
X-lied adrenoleukodystrophy
897
Where does ketogenesis occur?
Liver mitochondria
898
Products of ketogenesis
Acetoacetate and B-hydroxybutyrate (fuel)
| Acetone (cannot be used as fuel)
899
Rate limiting step of ketogenesis
Acetoacetyl CoA + acetyl CoA --(HMG CoA synthase)--> HMG CoA
900
What are the initial products that lead to the formation of acetyl CoA in ketogenolysis?
B-hydroxybutyrate -> acetoacetate -> acetyl coa
901
What peripheral tissues can oxidize ketone bodes?
Those with mitochondria like the renal cortex, brain, and skeletal muscle
902
Why cant liver convert acetoacetate to acetyl CoA?
It lacks succinyl-CoA acetoacetyl-CoA reductase (thiophorase)
903
What is the Urine test for ketones? What ketone type does not it detect?
Nitroprusside test
Does not detect b-hydroxybutyrate
904
Which part of cholesterol can a fatty acid attach to form a cholesteryl ester?
Single hydroxyl group of carbon 3 of the alpha ring
905
Where does cholesterol synthesis occur?
All cells in the Cytosol and SER majority of which are found in the liver and intestines
906
Substrates of cholesterol synthesis
Acetyl CoA, NADPH, ATP
907
Rate limiting step in cholesterol synthesis
HMG CoA --(HMG CoA reductase)--> mevalonate
908
Steps in Cholestid synthesis
1. Biosynthesis of mevalonate
2. Formation of isoprenoid units
3. Isoprene unit is formed from 6 isoprenoid units
4. Formation of lanosterol
5. Formation of cholesterol
909
How is the cholesterol ring eliminated?
Through conversion to bile salts then secretion to bile
910
Bile acid synthesis, found in the liver and Cytosol, rate limiting enzyme is?
Cholesterol-7-a-hydroxylase
911
What are the primary bile acids?
Cholic acid
| Chenocholic acid
912
What are the two amino acids used in bile acid conjugation to form bile salts?
Taurine and glycine
913
What are the secondary bile acids?
Deoxycholic acid
| Lithocholic acid
914
Where does steroid hormone synthesis occur?
SER of the adrenal glands, ovaries and testes, and placenta
915
What is blocked by the drug aminogluthetimide?
The conversion of cholesterol to pregnenolone by desmolase
916
The enzyme responsible for the breakdown of TAG to FA and:
A) 2-MAG from diet
B) FREE glycerol from chylomicrons and VLDL
C) 2-MAG from adipose
A) pancreatic lipase
B) Lipoprotein lipase
C) hormone sensitive lipase
917
Lipoprotein with the largest percentage of TG
Chylomicrons
918
Lipoprotein with the largest percentage of cholesteryl esters
LDL
919
Chylomicrons transport TG and cholesterol from where to where?
Intestines to tissues
920
VLDL transports TG from where to where?
Liver to tissues
921
What apoprotein activates lipoprotein lipase?
APO-CII
922
What apolipoprotein uptakes remnants by the liver?
APO E
923
Apolipoprotein B-48 is used by chylomicrons which are created by the?
Epithelial cells
924
What apolipoprotein is secreted by the liver for VDL?
B-100
925
How does IDL become LDL?
By picking up cholesterol from HD!
926
Which apoprotein delivers cholesterol into cells?
LDL
927
Which apolipoprotein is used by HDL to activate lecithin cholesterol acyl transferase or LCAT to produce cholesterol esters?
APO-A1
928
Difference between Type II familial hypercholesterolemia and type IV familial hypertriglyceredemia?
The former has high LDL leader to xanthomas and xanthelasmas with increased risk of atherosclerosis and CHD
The latter has increased VLDL production leading to a triad of
1. DM type 2
2. CAD
3. Obesity
929
Phospholipid is composed of
DAG
Alcohol
Phosphodiester bond
930
Most abundant phospholipid which is important in nervous transmission
Phosphatidylcholine
931
Phospholipid playing a role in apoptosis
Phosphatidyl serine
932
Phospholipid that is a major component of surfactant?
Dipalmitoylphosphatidylcholine
933
Phospholipid reservoir for arachidonic acid in the membranes
Phosphatidylinositol
934
What phospholipid is essential in mitochondrial function which is also used as a non-troponemal test due to its ability to act as an antigen?
Cardiolipin
935
```
Composition of these glycolipids:
Ceramide
Cerebroside
Globoside
Ganglioside
Sulfatide
```
Ceramide: sphingosine + FA
```
Ceramide + ________
Glucose or galactose = Cerebroside
Oligosacchardide = Globoside
N-acetylneuramic acid = Ganglioside
Sulfated galactose = Sulfatide
```
936
Hexosaminidase a ficiency leading to Ssx like cherry red macula, MR, hypotonia
Tay-Sachs disease
937
A-galactosidase deficiency leading to 3Rs: recessive x-linked, rash, renal failure
Fabrys disease
938
B-glucosidase deficiency leading to hepatosplenomegaly and erosion of long bones
Gauchers dissease
939
Sphingomyelinase deficiency leading to hepatosplenomegaly
Nieman-pick disease
940
The set of all proteins expressed by an individual at a particular time
Proteome
941
Aims to identify the entire complement of proteins elaborated by a cell under diverse conditions
Proteomics
942
What amino acid is needed to form ALA in heme synthesis?
Glycine combined with succinyl CoA
943
Which amino acid carries nitrogen from the liver?
Alanine
944
Which amino acids are implicated in maple syrup disease
valine, lucine, isoleucine
945
What enzyme is responsible for the buildup of phenyl lactate, phenyl acetate, and phenylpyruvate?
Phenylalanine hydroxylase
946
What amino acid is the precursor for niacin, serotonin, and melatonin?
Serotonin
947
What is the amino acid precursor for homocysteine?
Methionine
948
What amino acid contributes to the fibrous structure of collagen and interrupts a-helices in globular proteins?
Proline
949
Increase of the combination of this Amino acid is responsible for the curly hair of people?
Cysteine + cysteine = cystine
950
Amino acids with sites for O-linked glycosylation in the Golgi apparatus?
Serine and threonine
951
Site for n-linked glycosylation in the ER
Asparagine
952
Amino acid deaminated by an enzyme which results in the formation of ammonia. This is the major carrier of nitrogen to the liver from peripheral tissues,
Glutaminase deaminates glutamine
953
Amino acid used in the determination for Folic acid deficiency. What is the test called?
Histidine used in the N-forminoglutamate excretion test
| Increased amounts of FIGu in urine by Folic acid deficient individuals after histindine intake
954
Precursor amino acid for creatinine, urea, nitric oxide
Arginine
955
Essential amino acids that cannot be synthesized by the body and must come from the diet
PVT TIM HALL always ARGues and never TYRes
Phenylalanine, valine, tryptophan, threonine' isoleucine, methionine, histidine, argenine, Leucine, Lysine
956
Heme is a complex of?
Protoporphorin IX and heme
957
What is the Bohr effect?
HBO2 + H+ HbH + O2
958
What is an oxidized for of HB (Fe 3+) that does not bind O2 readily which could lead to chocolate cyanosis ? It is treated with oral methylene blue or ascorbic acid up to IV methylene blue.
Methemoglobin
959
Hemoglobin bound to carbon monoxide instead of O2 leading to a cherry pink color.
Carboxyhemoglobin
960
HB bound to carbon dioxide is called
Carbaminohenoglobin
961
Classification of alpha and beta thalassemia
Alpha: silent carrier, a-thalassemia trait, Hb H disease, hydrops fetalis
Beta: B-thalassemia minor and major
962
Most frequently affected collagen in Ehler Danlos syndrome leading to hyper extensible skin, tendency to bleed, hyper mobile joints, and increased risk for berry aneurysms.
Collagen type 3
963
Collagen I mutation leading to bendable and easily fractured bones. Accompanied with blue sclerae, hearing loss, and dental imperfections.
Osteogenesis imperfecta
964
Vitamin C deficiency leading to decreased hydroxylation of collagen. This leads to sore spongy gums, loose teeth, poor wound healing, and petecchiae on skin and mucous membranes.
Scurvy
965
Type IV collagen defect leading to hematuria and ESRD
Alpert syndrome
966
Collagen defect leading to kinky hair due to a deficiency of copper required by lysyl oxidase to strengthen collagen fibers.
Menke syndrome
967
Skin breaking and blisters as a result for minor trauma. This disease is due to a defect in collage VII.
Epidermolysis bullosa
968
Like collagen elastin has pro line and Lysine but has little and no?
Hydroxyproline
| Hydroxylysine
969
Protein degradation mechanisms of nitrogen
Energy dependent ubiquitin-proteosome mechanism
| Non-energy dependent degradation enzyme
970
Phases in amino acid catabolism
First phase: removal of a-amino group forming ammonia and a corresponding ketoacid
Second phase: carbon skeletons of a-ketoacids are converted to common intermediates of energy producing metabolic pathwas
971
Two main steps in nitrogen removal from AA
1. Transamination
| 2. Oxidative deamination
972
Where does transamination occur?
All cells of the body
973
All but two amino acids transfer their amino groups to a-ketoglutarate except?
Lysine and threonine
974
What is the coenzyme for the two aminotransferases?
Pyridoxal phosphate (vitamin B6)
975
Oxidative deamination occurs where and for which amino acid only?
Liver and kidney
| Only glutamate
976
Glutamate is oxidized by glutamate dehydrogenases and deaminated to form ?
free ammonia which is used to make urea
977
What does the conversion of glutamate to a-ketoglutarate yield? What about vice versa?
Glutamate -> a ketoglutarate NH3 + NADH
| A ketoglutarate -> glutamate NADP+ + NH3
978
How is excess nitrogen removal from peripheral tissues removed?
1. Glutamine: via glutamate + ammonia (through Flutamide synthaetase)
2. Alanine: via glucose -> pyruvate + glutamate -> alanine cycle
979
Glutaminase deaminates glutamine to produce ammonium ion which is excreted from the body. Where are the two tissues this enzyme could be located?
Kidneys and small intestines
980
Another name for urea cycle
Ornithine cycle or krebs-henseleit cycle
981
What are the donors of the urea molecule?
1. NH3 from free ammonia
2. NH3 from aspartate
3. 1C and 1O from CO2
982
Reactions in the urea cycle
1. Formation of carbamoyl phosphate (via carbamoyl phosphate synthetase I)
2. Formation of citrulline (via Ornithine transcarbamoylase)
3. Synthesis of arginosuccinate (arginosuccinate synthetase)
4. Cleavage of arginosuccinate to form arginine (Arginosuccinase)
5. Arginine cleavage to yield urea and Ornithine (arginase)
983
Rate limiting step of urea cycle
Carbamoyl phosphate synthetase I
984
Energy requirement of urea cycle
4 ATP
985
Co factors of urea cycle
N-acetylglutamate
| Biotin
986
Hereditary hyperammonemia produces symptoms such as
Hyperammonemia, elevated blood glutamine, decreased BUN
| Parents with lethargy, vomiting, hyperventilation, convulsions, cerebral edema, coma, and death
987
Treatment for hereditary hyperammonemia
Low protein diet
| Administration of sodium benzoate or phenylpyruvate to capture and excrete excess nitrogen
988
Ketogenic carbon skeletons of AA
Leucine
Lysine
Yields acetoacetate or acetyl-coa/ acetoacetyl-coa
989
Ketogenic and glucogenic carbon skeletons of AA
```
WIFY
Phenylalanine
Isoleucine
Tryptophan
Tyrosine
```
Yields Ketogenic and glucose or glycogen by products
990
This amino acid acts as a raw material in the biosynthesis of Heme, purines, creatine
Glycine
991
This amino acid acts as a raw material in the biosynthesis of phospholipid, sphingolipid, purines, thymine
Serine
992
This amino acid acts as a raw material in the biosynthesis of GABA
Glutamate
993
This amino acid acts as a raw material in the biosynthesis of creatine, polyamines, nitric oxide
Arginine
994
This amino acid acts as a raw material in the biosynthesis of serotonin, NAD+, NADP+, melatonin
Tryptophan
995
This amino acid acts as a raw material in the biosynthesis of catecholamines, thyroid hormones, melanin
Tyrosine
996
3 hormones dependent on tyrosine
Thyroid hormones
Melanin
Catecholamines
997
Deficiency of homogenistic acid oxidase in the degrative pathway of tyrosine which results in urine turning to black on standing with dark connective tissues (ochronosis)
Alkaptonuria
998
Congenital deficiency due tyrosinase deficieny or defective tyrosine transporters which leads to an increased risk for skin cancer.
Albinism
999
Autosomal recessive disorder that may either be due to decreased methionine, increased cysteine, B6, and folate or decreased affinity for cystathione synthase. This results in mental retardation, osteoporosis, tall stature, lens subluxation, and atherosclerosis.
Homocystinuria
1000
Common inherited defect of renal tubular amino acid transporter for its parent compound, Ornithine, Lysine, and arginine, in the PCT of the kidneys. It eventually precipitates and cause staghorn caliculi. What is its treatment?
Cystinuria is treated with acetazolamide to alkalinize the urine
1001
The initial and last three steps of heme synthesis occurs in?
The mitochondria
1002
Heme synthesis summary
1. Formation of ALA (via ALA synthase and B6)
2. Formation of porphobilinogen
3. Formation of uroporphyrinogen
4. Formation of heme
1003
Lead inhibits what two steps in heme synthesis?
1. Introduction of Fe 2+ into protoporphyrin IX via ferrochelatase
2. Condensation of two ALA molecules by zinc containing ALA dehydratase
1004
Where is B6 a cofactors of?
1. Heme synthesis
2. Synthesis of cystathionine from homocysteine
3. Transamination between alanine and a-ketoglutarate
1005
Most common porphyria
Porphyria cutanea tarda
1006
Which part of heme synthesis do these symptoms appear?
1. Photosensitivity
2. Neuropsychiatric symptoms
1. After ring formation
| 2. Before ring formation
1007
Pyridoxine ficiency associated with isoniazid therapy results in this histopathologic finding
Sideroblastic anemia with ringed sideroblast
1008
Poisoning due to this heavy metal leads to coar basophilic stippling of RBC, peripheral neuropathy, lines in gums, increas in urinary ALA and free erythrocytes porphorin
lead poisoning
1009
Microcytic hypo chromic anemia is found in
IDA
Thalassemia
Lead poisoning
1010
Megaloblastic anemia is found in
Folate or B12 deficiency
| Pernicious anemia
1011
Normoyctic normochromic anemia is found in
Anemia of chronic kidney disease
| Blood loss
1012
Increase in MCHC is found in
Hereditary spherocytosis
1013
Summary of heme degradation
1. Formation of bilirubin
2. Uptake of bilirubin by the liver
3. Formation of bilirubin diglucoronide
4. Secretion of bilirubin into bile
5. Formation of urobilins in the intestine
1014
Colors of biliverdin, bilirubin, urobilinogen, stercolin, urobilin
```
Biliverdin: green
Bilirubin: red orange
Urobilinogen: colorless
Stercolin: brown orange red
Urobilin: yellow
```
1015
Examples of unconjugated hyperbilirubinemia
```
Hemolytic anemia
Physiologic jaundice
Crigler-najjar syndrome types I and II
Gilbert syndrome
Toxic hyperbilirubinemia
```
1016
Examples of conjugated hyperbilirubinemia
Biliary tree obstruction
Dubin-Johnson syndrome
Rotor syndrome
1017
What reaction measures total and direct bilirubin?
Van den bergs reaction
1018
What enzyme activates fatty acid for metabolism use?
Fatty-acyl-CoA synthetase
1019
Cofactor required for fatty acid activation
Vitamin B5 or Panthotenic acid
1020
Energy required to activate fatty acid
2 ATP
1021
What is the product formed in fatty acid synthesis?
Palmitate (16:0)
1022
Where does fatty acid synthesis occur?
Cytosol
Major: Liver and lactating mammary glands
Minor: adipose tissue
1023
Substrates for fatty acid synthesis
1 acetyl CoA
7 malonyl CoA
NADPH
ATP
1024
Rate limiting step in fatty acid synthesis
Acetyl CoA + ATP -> malonyl CoA
| Enzyme: acetyl CoA carboxylase
1025
Steps in fatty acid synthesis
1. Synthesis of cytoplasmic acetyl CoA (transfer of mitochondrial acetyl CoA to cytoplasm via citrate shuttle)
2. Acetyl CoA carboxylation to malonyl CoA (via acetyl CoA carboxylase with biotin) [+ insulin, citrate]
3. Assembly of palmitate (via fatty acid synthase and Vit B5)
1026
Steps in palmitate assembly
1. Condensation
2. Reduction
3. Dehydration
4. Reduction
1027
What is the fate of Palmitate after its production?
1. Further elongation in SER and mitochondria
| 2. Desaturated in the ER (but not past the 9th carbon)
1028
Main storage form of fatty acids
Triacylglycerols
1029
Where does TAG synthesis occur?
Liver and adipose tissue
1030
Sources of glycerol-3-phosphate
1. DHAP from glycolysis (liver and adipose)
| 2. Phosphorylation of free glycerol (liver)
1031
What enzyme is responsible for the release of free fatty acids from TAGs?
Hormone sensitive lipases
1032
In the bloodstream fatty acids are always bound to?
Albumin
1033
Hormone sensitive lipases can only release what free fatty acids stored in TAG?
C1 & 3 thus resulting in
TAG -> 2 free FA and 2-mono acyl glycerol
1034
Where does B-oxidation of fatty acids occur
Mitochondria of all cells, but the fatty acid activation raft occurs in the Cytosol
Exception: RBC, kidney medulla, neurons, testes
1035
Rate limiting step in B-oxidation
Fatty acyl CoA + carnitine -> fatty acyl carnitine + CoA
| Enzyme: carnitine acyl transferase I
1036
Cutoff number of carbons that do not need a shuttle
Less than 12 carbons
1037
Steps in the carnitine shuttle
1. Fatty acyl synthase activates the fatty acid
2. Carnitine acyl transferase 1 attaches to fatty acyl to carnitine in the outer mitochondrial membrane
3. Fatty acyl-carnitine is shuttle through the inner membrane
4. Carnitine acyl transferase-2 transfers fatty acyl group back to a CoA in the mitochondrial matrix
1038
Steps in beta oxidation
1. Oxidation
2. Hydratiion
3. Oxidation
4. Thiolysis
1039
Beta oxidation of fatty acids with an odd number of carbon atoms releases?
Propionyl CoA which is converted to methylmalonyl coa (requires B12) then to succinyl CoA
1040
Which is responsible for the conversion of very long chain fatty acids?
Peroxisomes but if unsaturated it requires 3,2 enol-CoA isomerase
1041
Energy yield in ATP of beta oxidation of palmitate
129 ATP
7 NADH= 21
7 FAD= 14
8 acetyl CoA= 96
Activation = -2
1042
Intake of this compound depletes the body's NAD+ supply leading to accumulation Of fat in the liver
Alcohol
1043
Type of carnitine deficiency which leads to impaired FA oxidation and ketogenesis with hypoglycemia?
CPT-1 deficiency
1044
Type of carnitine deficiency which affects skeletal muscle and when severe the liver
CPT-2 deficiency
1045
It is a disorder school results in decreased fatty acid oxidation. Without the ATP to support gluconeogenesis, hypoglycemia becomes profound which may eventually leads to SIDS. It is prevented by frequent feeding with high carbohydrate and low fat diet.
Medium-chain fatty acyl-CoA dehydrogenase (MCAD) deficiency
1046
Associated with eating unripe fruit of the akee tree which contains hypoglycin thus activating MC and SC acyl CoA dehydrogenase
Jamaican vomiting sickness
1047
Rare neurological disorder which results to the accumulation of phytanic acid found in plant food stuff which blocks Boxidation
Refsum disease
1048
Cerebrohepatorenal syndrome resulting from the absence of peroxisomes in all tissues, it is characterized by liver dysfunction, jaundice, MR, weakness, hypotonia, and craniofacial dimorphism
Zellweger syndrome
1049
Defect in peroxismal activation of VLCFA thus leading to its accumulation. Ssx: apathy, behavral change, then visual loss spasticity, ataxia. All due to the fact since VLCFA are found in myelin tissue.
X-lied adrenoleukodystrophy
1050
Where does ketogenesis occur?
Liver mitochondria
1051
Products of ketogenesis
Acetoacetate and B-hydroxybutyrate (fuel)
| Acetone (cannot be used as fuel)
1052
Rate limiting step of ketogenesis
Acetoacetyl CoA + acetyl CoA --(HMG CoA synthase)--> HMG CoA
1053
What are the initial products that lead to the formation of acetyl CoA in ketogenolysis?
B-hydroxybutyrate -> acetoacetate -> acetyl coa
1054
What peripheral tissues can oxidize ketone bodes?
Those with mitochondria like the renal cortex, brain, and skeletal muscle
1055
Why cant liver convert acetoacetate to acetyl CoA?
It lacks succinyl-CoA acetoacetyl-CoA reductase (thiophorase)
1056
What is the Urine test for ketones? What ketone type does not it detect?
Nitroprusside test
Does not detect b-hydroxybutyrate
1057
Which part of cholesterol can a fatty acid attach to form a cholesteryl ester?
Single hydroxyl group of carbon 3 of the alpha ring
1058
Where does cholesterol synthesis occur?
All cells in the Cytosol and SER majority of which are found in the liver and intestines
1059
Substrates of cholesterol synthesis
Acetyl CoA, NADPH, ATP
1060
Rate limiting step in cholesterol synthesis
HMG CoA --(HMG CoA reductase)--> mevalonate
1061
Steps in Cholestid synthesis
1. Biosynthesis of mevalonate
2. Formation of isoprenoid units
3. Isoprene unit is formed from 6 isoprenoid units
4. Formation of lanosterol
5. Formation of cholesterol
1062
How is the cholesterol ring eliminated?
Through conversion to bile salts then secretion to bile
1063
Bile acid synthesis, found in the liver and Cytosol, rate limiting enzyme is?
Cholesterol-7-a-hydroxylase
1064
What are the primary bile acids?
Cholic acid
| Chenocholic acid
1065
What are the two amino acids used in bile acid conjugation to form bile salts?
Taurine and glycine
1066
What are the secondary bile acids?
Deoxycholic acid
| Lithocholic acid
1067
Where does steroid hormone synthesis occur?
SER of the adrenal glands, ovaries and testes, and placenta
1068
What is blocked by the drug aminogluthetimide?
The conversion of cholesterol to pregnenolone by desmolase
1069
The enzyme responsible for the breakdown of TAG to FA and:
A) 2-MAG from diet
B) FREE glycerol from chylomicrons and VLDL
C) 2-MAG from adipose
A) pancreatic lipase
B) Lipoprotein lipase
C) hormone sensitive lipase
1070
Lipoprotein with the largest percentage of TG
Chylomicrons
1071
Lipoprotein with the largest percentage of cholesteryl esters
LDL
1072
Chylomicrons transport TG and cholesterol from where to where?
Intestines to tissues
1073
VLDL transports TG from where to where?
Liver to tissues
1074
What apoprotein activates lipoprotein lipase?
APO-CII
1075
What apolipoprotein uptakes remnants by the liver?
APO E
1076
Apolipoprotein B-48 is used by chylomicrons which are created by the?
Epithelial cells
1077
What apolipoprotein is secreted by the liver for VDL?
B-100
1078
How does IDL become LDL?
By picking up cholesterol from HD!
1079
Which apoprotein delivers cholesterol into cells?
LDL
1080
Which apolipoprotein is used by HDL to activate lecithin cholesterol acyl transferase or LCAT to produce cholesterol esters?
APO-A1
1081
Difference between Type II familial hypercholesterolemia and type IV familial hypertriglyceredemia?
The former has high LDL leader to xanthomas and xanthelasmas with increased risk of atherosclerosis and CHD
The latter has increased VLDL production leading to a triad of
1. DM type 2
2. CAD
3. Obesity
1082
Phospholipid is composed of
DAG
Alcohol
Phosphodiester bond
1083
Most abundant phospholipid which is important in nervous transmission
Phosphatidylcholine
1084
Phospholipid playing a role in apoptosis
Phosphatidyl serine
1085
Phospholipid that is a major component of surfactant?
Dipalmitoylphosphatidylcholine
1086
Phospholipid reservoir for arachidonic acid in the membranes
Phosphatidylinositol
1087
What phospholipid is essential in mitochondrial function which is also used as a non-troponemal test due to its ability to act as an antigen?
Cardiolipin
1088
```
Composition of these glycolipids:
Ceramide
Cerebroside
Globoside
Ganglioside
Sulfatide
```
Ceramide: sphingosine + FA
```
Ceramide + ________
Glucose or galactose = Cerebroside
Oligosacchardide = Globoside
N-acetylneuramic acid = Ganglioside
Sulfated galactose = Sulfatide
```
1089
Hexosaminidase a ficiency leading to Ssx like cherry red macula, MR, hypotonia
Tay-Sachs disease
1090
A-galactosidase deficiency leading to 3Rs: recessive x-linked, rash, renal failure
Fabrys disease
1091
B-glucosidase deficiency leading to hepatosplenomegaly and erosion of long bones
Gauchers dissease
1092
Sphingomyelinase deficiency leading to hepatosplenomegaly
Nieman-pick disease
1093
The set of all proteins expressed by an individual at a particular time
Proteome
1094
Aims to identify the entire complement of proteins elaborated by a cell under diverse conditions
Proteomics
1095
What amino acid is needed to form ALA in heme synthesis?
Glycine combined with succinyl CoA
1096
Which amino acid carries nitrogen from the liver?
Alanine
1097
Which amino acids are implicated in maple syrup disease
valine, lucine, isoleucine
1098
What enzyme is responsible for the buildup of phenyl lactate, phenyl acetate, and phenylpyruvate?
Phenylalanine hydroxylase
1099
What amino acid is the precursor for niacin, serotonin, and melatonin?
Serotonin
1100
What is the amino acid precursor for homocysteine?
Methionine
1101
What amino acid contributes to the fibrous structure of collagen and interrupts a-helices in globular proteins?
Proline
1102
Increase of the combination of this Amino acid is responsible for the curly hair of people?
Cysteine + cysteine = cystine
1103
Amino acids with sites for O-linked glycosylation in the Golgi apparatus?
Serine and threonine
1104
Site for n-linked glycosylation in the ER
Asparagine
1105
Amino acid deaminated by an enzyme which results in the formation of ammonia. This is the major carrier of nitrogen to the liver from peripheral tissues,
Glutaminase deaminates glutamine
1106
Amino acid used in the determination for Folic acid deficiency. What is the test called?
Histidine used in the N-forminoglutamate excretion test
| Increased amounts of FIGu in urine by Folic acid deficient individuals after histindine intake
1107
Precursor amino acid for creatinine, urea, nitric oxide
Arginine
1108
Essential amino acids that cannot be synthesized by the body and must come from the diet
PVT TIM HALL always ARGues and never TYRes
Phenylalanine, valine, tryptophan, threonine' isoleucine, methionine, histidine, argenine, Leucine, Lysine
1109
Heme is a complex of?
Protoporphorin IX and heme
1110
What is the Bohr effect?
HBO2 + H+ HbH + O2
1111
What is an oxidized for of HB (Fe 3+) that does not bind O2 readily which could lead to chocolate cyanosis ? It is treated with oral methylene blue or ascorbic acid up to IV methylene blue.
Methemoglobin
1112
Hemoglobin bound to carbon monoxide instead of O2 leading to a cherry pink color.
Carboxyhemoglobin
1113
HB bound to carbon dioxide is called
Carbaminohenoglobin
1114
Classification of alpha and beta thalassemia
Alpha: silent carrier, a-thalassemia trait, Hb H disease, hydrops fetalis
Beta: B-thalassemia minor and major
1115
Most frequently affected collagen in Ehler Danlos syndrome leading to hyper extensible skin, tendency to bleed, hyper mobile joints, and increased risk for berry aneurysms.
Collagen type 3
1116
Collagen I mutation leading to bendable and easily fractured bones. Accompanied with blue sclerae, hearing loss, and dental imperfections.
Osteogenesis imperfecta
1117
Vitamin C deficiency leading to decreased hydroxylation of collagen. This leads to sore spongy gums, loose teeth, poor wound healing, and petecchiae on skin and mucous membranes.
Scurvy
1118
Type IV collagen defect leading to hematuria and ESRD
Alpert syndrome
1119
Collagen defect leading to kinky hair due to a deficiency of copper required by lysyl oxidase to strengthen collagen fibers.
Menke syndrome
1120
Skin breaking and blisters as a result for minor trauma. This disease is due to a defect in collage VII.
Epidermolysis bullosa
1121
Like collagen elastin has pro line and Lysine but has little and no?
Hydroxyproline
| Hydroxylysine
1122
Protein degradation mechanisms of nitrogen
Energy dependent ubiquitin-proteosome mechanism
| Non-energy dependent degradation enzyme
1123
Phases in amino acid catabolism
First phase: removal of a-amino group forming ammonia and a corresponding ketoacid
Second phase: carbon skeletons of a-ketoacids are converted to common intermediates of energy producing metabolic pathwas
1124
Two main steps in nitrogen removal from AA
1. Transamination
| 2. Oxidative deamination
1125
Where does transamination occur?
All cells of the body
1126
All but two amino acids transfer their amino groups to a-ketoglutarate except?
Lysine and threonine
1127
What is the coenzyme for the two aminotransferases?
Pyridoxal phosphate (vitamin B6)
1128
Oxidative deamination occurs where and for which amino acid only?
Liver and kidney
| Only glutamate
1129
Glutamate is oxidized by glutamate dehydrogenases and deaminated to form ?
free ammonia which is used to make urea
1130
What does the conversion of glutamate to a-ketoglutarate yield? What about vice versa?
Glutamate -> a ketoglutarate NH3 + NADH
| A ketoglutarate -> glutamate NADP+ + NH3
1131
How is excess nitrogen removal from peripheral tissues removed?
1. Glutamine: via glutamate + ammonia (through Flutamide synthaetase)
2. Alanine: via glucose -> pyruvate + glutamate -> alanine cycle
1132
Glutaminase deaminates glutamine to produce ammonium ion which is excreted from the body. Where are the two tissues this enzyme could be located?
Kidneys and small intestines
1133
Another name for urea cycle
Ornithine cycle or krebs-henseleit cycle
1134
What are the donors of the urea molecule?
1. NH3 from free ammonia
2. NH3 from aspartate
3. 1C and 1O from CO2
1135
Reactions in the urea cycle
1. Formation of carbamoyl phosphate (via carbamoyl phosphate synthetase I)
2. Formation of citrulline (via Ornithine transcarbamoylase)
3. Synthesis of arginosuccinate (arginosuccinate synthetase)
4. Cleavage of arginosuccinate to form arginine (Arginosuccinase)
5. Arginine cleavage to yield urea and Ornithine (arginase)
1136
Rate limiting step of urea cycle
Carbamoyl phosphate synthetase I
1137
Energy requirement of urea cycle
4 ATP
1138
Co factors of urea cycle
N-acetylglutamate
| Biotin
1139
Hereditary hyperammonemia produces symptoms such as
Hyperammonemia, elevated blood glutamine, decreased BUN
| Parents with lethargy, vomiting, hyperventilation, convulsions, cerebral edema, coma, and death
1140
Treatment for hereditary hyperammonemia
Low protein diet
| Administration of sodium benzoate or phenylpyruvate to capture and excrete excess nitrogen
1141
Ketogenic carbon skeletons of AA
Leucine
Lysine
Yields acetoacetate or acetyl-coa/ acetoacetyl-coa
1142
Ketogenic and glucogenic carbon skeletons of AA
```
WIFY
Phenylalanine
Isoleucine
Tryptophan
Tyrosine
```
Yields Ketogenic and glucose or glycogen by products
1143
This amino acid acts as a raw material in the biosynthesis of Heme, purines, creatine
Glycine
1144
This amino acid acts as a raw material in the biosynthesis of phospholipid, sphingolipid, purines, thymine
Serine
1145
This amino acid acts as a raw material in the biosynthesis of GABA
Glutamate
1146
This amino acid acts as a raw material in the biosynthesis of creatine, polyamines, nitric oxide
Arginine
1147
This amino acid acts as a raw material in the biosynthesis of serotonin, NAD+, NADP+, melatonin
Tryptophan
1148
This amino acid acts as a raw material in the biosynthesis of catecholamines, thyroid hormones, melanin
Tyrosine
1149
3 hormones dependent on tyrosine
Thyroid hormones
Melanin
Catecholamines
1150
Deficiency of homogenistic acid oxidase in the degrative pathway of tyrosine which results in urine turning to black on standing with dark connective tissues (ochronosis)
Alkaptonuria
1151
Congenital deficiency due tyrosinase deficieny or defective tyrosine transporters which leads to an increased risk for skin cancer.
Albinism
1152
Autosomal recessive disorder that may either be due to decreased methionine, increased cysteine, B6, and folate or decreased affinity for cystathione synthase. This results in mental retardation, osteoporosis, tall stature, lens subluxation, and atherosclerosis.
Homocystinuria
1153
Common inherited defect of renal tubular amino acid transporter for its parent compound, Ornithine, Lysine, and arginine, in the PCT of the kidneys. It eventually precipitates and cause staghorn caliculi. What is its treatment?
Cystinuria is treated with acetazolamide to alkalinize the urine
1154
The initial and last three steps of heme synthesis occurs in?
The mitochondria
1155
Heme synthesis summary
1. Formation of ALA (via ALA synthase and B6)
2. Formation of porphobilinogen
3. Formation of uroporphyrinogen
4. Formation of heme
1156
Lead inhibits what two steps in heme synthesis?
1. Introduction of Fe 2+ into protoporphyrin IX via ferrochelatase
2. Condensation of two ALA molecules by zinc containing ALA dehydratase
1157
Where is B6 a cofactors of?
1. Heme synthesis
2. Synthesis of cystathionine from homocysteine
3. Transamination between alanine and a-ketoglutarate
1158
Most common porphyria
Porphyria cutanea tarda
1159
Which part of heme synthesis do these symptoms appear?
1. Photosensitivity
2. Neuropsychiatric symptoms
1. After ring formation
| 2. Before ring formation
1160
Pyridoxine ficiency associated with isoniazid therapy results in this histopathologic finding
Sideroblastic anemia with ringed sideroblast
1161
Poisoning due to this heavy metal leads to coar basophilic stippling of RBC, peripheral neuropathy, lines in gums, increas in urinary ALA and free erythrocytes porphorin
lead poisoning
1162
Microcytic hypo chromic anemia is found in
IDA
Thalassemia
Lead poisoning
1163
Megaloblastic anemia is found in
Folate or B12 deficiency
| Pernicious anemia
1164
Normoyctic normochromic anemia is found in
Anemia of chronic kidney disease
| Blood loss
1165
Increase in MCHC is found in
Hereditary spherocytosis
1166
Summary of heme degradation
1. Formation of bilirubin
2. Uptake of bilirubin by the liver
3. Formation of bilirubin diglucoronide
4. Secretion of bilirubin into bile
5. Formation of urobilins in the intestine
1167
Colors of biliverdin, bilirubin, urobilinogen, stercolin, urobilin
```
Biliverdin: green
Bilirubin: red orange
Urobilinogen: colorless
Stercolin: brown orange red
Urobilin: yellow
```
1168
Examples of unconjugated hyperbilirubinemia
```
Hemolytic anemia
Physiologic jaundice
Crigler-najjar syndrome types I and II
Gilbert syndrome
Toxic hyperbilirubinemia
```
1169
Examples of conjugated hyperbilirubinemia
Biliary tree obstruction
Dubin-Johnson syndrome
Rotor syndrome
1170
What reaction measures total and direct bilirubin?
Van den bergs reaction
1171
What enzyme activates fatty acid for metabolism use?
Fatty-acyl-CoA synthetase
1172
Cofactor required for fatty acid activation
Vitamin B5 or Panthotenic acid
1173
Energy required to activate fatty acid
2 ATP
1174
What is the product formed in fatty acid synthesis?
Palmitate (16:0)
1175
Where does fatty acid synthesis occur?
Cytosol
Major: Liver and lactating mammary glands
Minor: adipose tissue
1176
Substrates for fatty acid synthesis
1 acetyl CoA
7 malonyl CoA
NADPH
ATP
1177
Rate limiting step in fatty acid synthesis
Acetyl CoA + ATP -> malonyl CoA
| Enzyme: acetyl CoA carboxylase
1178
Steps in fatty acid synthesis
1. Synthesis of cytoplasmic acetyl CoA (transfer of mitochondrial acetyl CoA to cytoplasm via citrate shuttle)
2. Acetyl CoA carboxylation to malonyl CoA (via acetyl CoA carboxylase with biotin) [+ insulin, citrate]
3. Assembly of palmitate (via fatty acid synthase and Vit B5)
1179
Steps in palmitate assembly
1. Condensation
2. Reduction
3. Dehydration
4. Reduction
1180
What is the fate of Palmitate after its production?
1. Further elongation in SER and mitochondria
| 2. Desaturated in the ER (but not past the 9th carbon)
1181
Main storage form of fatty acids
Triacylglycerols
1182
Where does TAG synthesis occur?
Liver and adipose tissue
1183
Sources of glycerol-3-phosphate
1. DHAP from glycolysis (liver and adipose)
| 2. Phosphorylation of free glycerol (liver)
1184
What enzyme is responsible for the release of free fatty acids from TAGs?
Hormone sensitive lipases
1185
In the bloodstream fatty acids are always bound to?
Albumin
1186
Hormone sensitive lipases can only release what free fatty acids stored in TAG?
C1 & 3 thus resulting in
TAG -> 2 free FA and 2-mono acyl glycerol
1187
Where does B-oxidation of fatty acids occur
Mitochondria of all cells, but the fatty acid activation raft occurs in the Cytosol
Exception: RBC, kidney medulla, neurons, testes
1188
Rate limiting step in B-oxidation
Fatty acyl CoA + carnitine -> fatty acyl carnitine + CoA
| Enzyme: carnitine acyl transferase I
1189
Cutoff number of carbons that do not need a shuttle
Less than 12 carbons
1190
Steps in the carnitine shuttle
1. Fatty acyl synthase activates the fatty acid
2. Carnitine acyl transferase 1 attaches to fatty acyl to carnitine in the outer mitochondrial membrane
3. Fatty acyl-carnitine is shuttle through the inner membrane
4. Carnitine acyl transferase-2 transfers fatty acyl group back to a CoA in the mitochondrial matrix
1191
Steps in beta oxidation
1. Oxidation
2. Hydratiion
3. Oxidation
4. Thiolysis
1192
Beta oxidation of fatty acids with an odd number of carbon atoms releases?
Propionyl CoA which is converted to methylmalonyl coa (requires B12) then to succinyl CoA
1193
Which is responsible for the conversion of very long chain fatty acids?
Peroxisomes but if unsaturated it requires 3,2 enol-CoA isomerase
1194
Energy yield in ATP of beta oxidation of palmitate
129 ATP
7 NADH= 21
7 FAD= 14
8 acetyl CoA= 96
Activation = -2
1195
Intake of this compound depletes the body's NAD+ supply leading to accumulation Of fat in the liver
Alcohol
1196
Type of carnitine deficiency which leads to impaired FA oxidation and ketogenesis with hypoglycemia?
CPT-1 deficiency
1197
Type of carnitine deficiency which affects skeletal muscle and when severe the liver
CPT-2 deficiency
1198
It is a disorder school results in decreased fatty acid oxidation. Without the ATP to support gluconeogenesis, hypoglycemia becomes profound which may eventually leads to SIDS. It is prevented by frequent feeding with high carbohydrate and low fat diet.
Medium-chain fatty acyl-CoA dehydrogenase (MCAD) deficiency
1199
Associated with eating unripe fruit of the akee tree which contains hypoglycin thus activating MC and SC acyl CoA dehydrogenase
Jamaican vomiting sickness
1200
Rare neurological disorder which results to the accumulation of phytanic acid found in plant food stuff which blocks Boxidation
Refsum disease
1201
Cerebrohepatorenal syndrome resulting from the absence of peroxisomes in all tissues, it is characterized by liver dysfunction, jaundice, MR, weakness, hypotonia, and craniofacial dimorphism
Zellweger syndrome
1202
Defect in peroxismal activation of VLCFA thus leading to its accumulation. Ssx: apathy, behavral change, then visual loss spasticity, ataxia. All due to the fact since VLCFA are found in myelin tissue.
X-lied adrenoleukodystrophy
1203
Where does ketogenesis occur?
Liver mitochondria
1204
Products of ketogenesis
Acetoacetate and B-hydroxybutyrate (fuel)
| Acetone (cannot be used as fuel)
1205
Rate limiting step of ketogenesis
Acetoacetyl CoA + acetyl CoA --(HMG CoA synthase)--> HMG CoA
1206
What are the initial products that lead to the formation of acetyl CoA in ketogenolysis?
B-hydroxybutyrate -> acetoacetate -> acetyl coa
1207
What peripheral tissues can oxidize ketone bodes?
Those with mitochondria like the renal cortex, brain, and skeletal muscle
1208
Why cant liver convert acetoacetate to acetyl CoA?
It lacks succinyl-CoA acetoacetyl-CoA reductase (thiophorase)
1209
What is the Urine test for ketones? What ketone type does not it detect?
Nitroprusside test
Does not detect b-hydroxybutyrate
1210
Which part of cholesterol can a fatty acid attach to form a cholesteryl ester?
Single hydroxyl group of carbon 3 of the alpha ring
1211
Where does cholesterol synthesis occur?
All cells in the Cytosol and SER majority of which are found in the liver and intestines
1212
Substrates of cholesterol synthesis
Acetyl CoA, NADPH, ATP
1213
Rate limiting step in cholesterol synthesis
HMG CoA --(HMG CoA reductase)--> mevalonate
1214
Steps in Cholestid synthesis
1. Biosynthesis of mevalonate
2. Formation of isoprenoid units
3. Isoprene unit is formed from 6 isoprenoid units
4. Formation of lanosterol
5. Formation of cholesterol
1215
How is the cholesterol ring eliminated?
Through conversion to bile salts then secretion to bile
1216
Bile acid synthesis, found in the liver and Cytosol, rate limiting enzyme is?
Cholesterol-7-a-hydroxylase
1217
What are the primary bile acids?
Cholic acid
| Chenocholic acid
1218
What are the two amino acids used in bile acid conjugation to form bile salts?
Taurine and glycine
1219
What are the secondary bile acids?
Deoxycholic acid
| Lithocholic acid
1220
Where does steroid hormone synthesis occur?
SER of the adrenal glands, ovaries and testes, and placenta
1221
What is blocked by the drug aminogluthetimide?
The conversion of cholesterol to pregnenolone by desmolase
1222
The enzyme responsible for the breakdown of TAG to FA and:
A) 2-MAG from diet
B) FREE glycerol from chylomicrons and VLDL
C) 2-MAG from adipose
A) pancreatic lipase
B) Lipoprotein lipase
C) hormone sensitive lipase
1223
Lipoprotein with the largest percentage of TG
Chylomicrons
1224
Lipoprotein with the largest percentage of cholesteryl esters
LDL
1225
Chylomicrons transport TG and cholesterol from where to where?
Intestines to tissues
1226
VLDL transports TG from where to where?
Liver to tissues
1227
What apoprotein activates lipoprotein lipase?
APO-CII
1228
What apolipoprotein uptakes remnants by the liver?
APO E
1229
Apolipoprotein B-48 is used by chylomicrons which are created by the?
Epithelial cells
1230
What apolipoprotein is secreted by the liver for VDL?
B-100
1231
How does IDL become LDL?
By picking up cholesterol from HD!
1232
Which apoprotein delivers cholesterol into cells?
LDL
1233
Which apolipoprotein is used by HDL to activate lecithin cholesterol acyl transferase or LCAT to produce cholesterol esters?
APO-A1
1234
Difference between Type II familial hypercholesterolemia and type IV familial hypertriglyceredemia?
The former has high LDL leader to xanthomas and xanthelasmas with increased risk of atherosclerosis and CHD
The latter has increased VLDL production leading to a triad of
1. DM type 2
2. CAD
3. Obesity
1235
Phospholipid is composed of
DAG
Alcohol
Phosphodiester bond
1236
Most abundant phospholipid which is important in nervous transmission
Phosphatidylcholine
1237
Phospholipid playing a role in apoptosis
Phosphatidyl serine
1238
Phospholipid that is a major component of surfactant?
Dipalmitoylphosphatidylcholine
1239
Phospholipid reservoir for arachidonic acid in the membranes
Phosphatidylinositol
1240
What phospholipid is essential in mitochondrial function which is also used as a non-troponemal test due to its ability to act as an antigen?
Cardiolipin
1241
```
Composition of these glycolipids:
Ceramide
Cerebroside
Globoside
Ganglioside
Sulfatide
```
Ceramide: sphingosine + FA
```
Ceramide + ________
Glucose or galactose = Cerebroside
Oligosacchardide = Globoside
N-acetylneuramic acid = Ganglioside
Sulfated galactose = Sulfatide
```
1242
Hexosaminidase a ficiency leading to Ssx like cherry red macula, MR, hypotonia
Tay-Sachs disease
1243
A-galactosidase deficiency leading to 3Rs: recessive x-linked, rash, renal failure
Fabrys disease
1244
B-glucosidase deficiency leading to hepatosplenomegaly and erosion of long bones
Gauchers dissease
1245
Sphingomyelinase deficiency leading to hepatosplenomegaly
Nieman-pick disease
1246
The set of all proteins expressed by an individual at a particular time
Proteome
1247
Aims to identify the entire complement of proteins elaborated by a cell under diverse conditions
Proteomics
1248
What amino acid is needed to form ALA in heme synthesis?
Glycine combined with succinyl CoA
1249
Which amino acid carries nitrogen from the liver?
Alanine
1250
Which amino acids are implicated in maple syrup disease
valine, lucine, isoleucine
1251
What enzyme is responsible for the buildup of phenyl lactate, phenyl acetate, and phenylpyruvate?
Phenylalanine hydroxylase
1252
What amino acid is the precursor for niacin, serotonin, and melatonin?
Serotonin
1253
What is the amino acid precursor for homocysteine?
Methionine
1254
What amino acid contributes to the fibrous structure of collagen and interrupts a-helices in globular proteins?
Proline
1255
Increase of the combination of this Amino acid is responsible for the curly hair of people?
Cysteine + cysteine = cystine
1256
Amino acids with sites for O-linked glycosylation in the Golgi apparatus?
Serine and threonine
1257
Site for n-linked glycosylation in the ER
Asparagine
1258
Amino acid deaminated by an enzyme which results in the formation of ammonia. This is the major carrier of nitrogen to the liver from peripheral tissues,
Glutaminase deaminates glutamine
1259
Amino acid used in the determination for Folic acid deficiency. What is the test called?
Histidine used in the N-forminoglutamate excretion test
| Increased amounts of FIGu in urine by Folic acid deficient individuals after histindine intake
1260
Precursor amino acid for creatinine, urea, nitric oxide
Arginine
1261
Essential amino acids that cannot be synthesized by the body and must come from the diet
PVT TIM HALL always ARGues and never TYRes
Phenylalanine, valine, tryptophan, threonine' isoleucine, methionine, histidine, argenine, Leucine, Lysine
1262
Heme is a complex of?
Protoporphorin IX and heme
1263
What is the Bohr effect?
HBO2 + H+ HbH + O2
1264
What is an oxidized for of HB (Fe 3+) that does not bind O2 readily which could lead to chocolate cyanosis ? It is treated with oral methylene blue or ascorbic acid up to IV methylene blue.
Methemoglobin
1265
Hemoglobin bound to carbon monoxide instead of O2 leading to a cherry pink color.
Carboxyhemoglobin
1266
HB bound to carbon dioxide is called
Carbaminohenoglobin
1267
Classification of alpha and beta thalassemia
Alpha: silent carrier, a-thalassemia trait, Hb H disease, hydrops fetalis
Beta: B-thalassemia minor and major
1268
Most frequently affected collagen in Ehler Danlos syndrome leading to hyper extensible skin, tendency to bleed, hyper mobile joints, and increased risk for berry aneurysms.
Collagen type 3
1269
Collagen I mutation leading to bendable and easily fractured bones. Accompanied with blue sclerae, hearing loss, and dental imperfections.
Osteogenesis imperfecta
1270
Vitamin C deficiency leading to decreased hydroxylation of collagen. This leads to sore spongy gums, loose teeth, poor wound healing, and petecchiae on skin and mucous membranes.
Scurvy
1271
Type IV collagen defect leading to hematuria and ESRD
Alpert syndrome
1272
Collagen defect leading to kinky hair due to a deficiency of copper required by lysyl oxidase to strengthen collagen fibers.
Menke syndrome
1273
Skin breaking and blisters as a result for minor trauma. This disease is due to a defect in collage VII.
Epidermolysis bullosa
1274
Like collagen elastin has pro line and Lysine but has little and no?
Hydroxyproline
| Hydroxylysine
1275
Protein degradation mechanisms of nitrogen
Energy dependent ubiquitin-proteosome mechanism
| Non-energy dependent degradation enzyme
1276
Phases in amino acid catabolism
First phase: removal of a-amino group forming ammonia and a corresponding ketoacid
Second phase: carbon skeletons of a-ketoacids are converted to common intermediates of energy producing metabolic pathwas
1277
Two main steps in nitrogen removal from AA
1. Transamination
| 2. Oxidative deamination
1278
Where does transamination occur?
All cells of the body
1279
All but two amino acids transfer their amino groups to a-ketoglutarate except?
Lysine and threonine
1280
What is the coenzyme for the two aminotransferases?
Pyridoxal phosphate (vitamin B6)
1281
Oxidative deamination occurs where and for which amino acid only?
Liver and kidney
| Only glutamate
1282
Glutamate is oxidized by glutamate dehydrogenases and deaminated to form ?
free ammonia which is used to make urea
1283
What does the conversion of glutamate to a-ketoglutarate yield? What about vice versa?
Glutamate -> a ketoglutarate NH3 + NADH
| A ketoglutarate -> glutamate NADP+ + NH3
1284
How is excess nitrogen removal from peripheral tissues removed?
1. Glutamine: via glutamate + ammonia (through Flutamide synthaetase)
2. Alanine: via glucose -> pyruvate + glutamate -> alanine cycle
1285
Glutaminase deaminates glutamine to produce ammonium ion which is excreted from the body. Where are the two tissues this enzyme could be located?
Kidneys and small intestines
1286
Another name for urea cycle
Ornithine cycle or krebs-henseleit cycle
1287
What are the donors of the urea molecule?
1. NH3 from free ammonia
2. NH3 from aspartate
3. 1C and 1O from CO2
1288
Reactions in the urea cycle
1. Formation of carbamoyl phosphate (via carbamoyl phosphate synthetase I)
2. Formation of citrulline (via Ornithine transcarbamoylase)
3. Synthesis of arginosuccinate (arginosuccinate synthetase)
4. Cleavage of arginosuccinate to form arginine (Arginosuccinase)
5. Arginine cleavage to yield urea and Ornithine (arginase)
1289
Rate limiting step of urea cycle
Carbamoyl phosphate synthetase I
1290
Energy requirement of urea cycle
4 ATP
1291
Co factors of urea cycle
N-acetylglutamate
| Biotin
1292
Hereditary hyperammonemia produces symptoms such as
Hyperammonemia, elevated blood glutamine, decreased BUN
| Parents with lethargy, vomiting, hyperventilation, convulsions, cerebral edema, coma, and death
1293
Treatment for hereditary hyperammonemia
Low protein diet
| Administration of sodium benzoate or phenylpyruvate to capture and excrete excess nitrogen
1294
Ketogenic carbon skeletons of AA
Leucine
Lysine
Yields acetoacetate or acetyl-coa/ acetoacetyl-coa
1295
Ketogenic and glucogenic carbon skeletons of AA
```
WIFY
Phenylalanine
Isoleucine
Tryptophan
Tyrosine
```
Yields Ketogenic and glucose or glycogen by products
1296
This amino acid acts as a raw material in the biosynthesis of Heme, purines, creatine
Glycine
1297
This amino acid acts as a raw material in the biosynthesis of phospholipid, sphingolipid, purines, thymine
Serine
1298
This amino acid acts as a raw material in the biosynthesis of GABA
Glutamate
1299
This amino acid acts as a raw material in the biosynthesis of creatine, polyamines, nitric oxide
Arginine
1300
This amino acid acts as a raw material in the biosynthesis of serotonin, NAD+, NADP+, melatonin
Tryptophan
1301
This amino acid acts as a raw material in the biosynthesis of catecholamines, thyroid hormones, melanin
Tyrosine
1302
3 hormones dependent on tyrosine
Thyroid hormones
Melanin
Catecholamines
1303
Deficiency of homogenistic acid oxidase in the degrative pathway of tyrosine which results in urine turning to black on standing with dark connective tissues (ochronosis)
Alkaptonuria
1304
Congenital deficiency due tyrosinase deficieny or defective tyrosine transporters which leads to an increased risk for skin cancer.
Albinism
1305
Autosomal recessive disorder that may either be due to decreased methionine, increased cysteine, B6, and folate or decreased affinity for cystathione synthase. This results in mental retardation, osteoporosis, tall stature, lens subluxation, and atherosclerosis.
Homocystinuria
1306
Common inherited defect of renal tubular amino acid transporter for its parent compound, Ornithine, Lysine, and arginine, in the PCT of the kidneys. It eventually precipitates and cause staghorn caliculi. What is its treatment?
Cystinuria is treated with acetazolamide to alkalinize the urine
1307
The initial and last three steps of heme synthesis occurs in?
The mitochondria
1308
Heme synthesis summary
1. Formation of ALA (via ALA synthase and B6)
2. Formation of porphobilinogen
3. Formation of uroporphyrinogen
4. Formation of heme
1309
Lead inhibits what two steps in heme synthesis?
1. Introduction of Fe 2+ into protoporphyrin IX via ferrochelatase
2. Condensation of two ALA molecules by zinc containing ALA dehydratase
1310
Where is B6 a cofactors of?
1. Heme synthesis
2. Synthesis of cystathionine from homocysteine
3. Transamination between alanine and a-ketoglutarate
1311
Most common porphyria
Porphyria cutanea tarda
1312
Which part of heme synthesis do these symptoms appear?
1. Photosensitivity
2. Neuropsychiatric symptoms
1. After ring formation
| 2. Before ring formation
1313
Pyridoxine ficiency associated with isoniazid therapy results in this histopathologic finding
Sideroblastic anemia with ringed sideroblast
1314
Poisoning due to this heavy metal leads to coar basophilic stippling of RBC, peripheral neuropathy, lines in gums, increas in urinary ALA and free erythrocytes porphorin
lead poisoning
1315
Microcytic hypo chromic anemia is found in
IDA
Thalassemia
Lead poisoning
1316
Megaloblastic anemia is found in
Folate or B12 deficiency
| Pernicious anemia
1317
Normoyctic normochromic anemia is found in
Anemia of chronic kidney disease
| Blood loss
1318
Increase in MCHC is found in
Hereditary spherocytosis
1319
What reaction measures total and direct bilirubin?
Van den bergs reaction
1320
Examples of conjugated hyperbilirubinemia
Biliary tree obstruction
Dubin-Johnson syndrome
Rotor syndrome
1321
Examples of unconjugated hyperbilirubinemia
```
Hemolytic anemia
Physiologic jaundice
Crigler-najjar syndrome types I and II
Gilbert syndrome
Toxic hyperbilirubinemia
```
1322
Colors of biliverdin, bilirubin, urobilinogen, stercolin, urobilin
```
Biliverdin: green
Bilirubin: red orange
Urobilinogen: colorless
Stercolin: brown orange red
Urobilin: yellow
```
1323
Summary of heme degradation
1. Formation of bilirubin
2. Uptake of bilirubin by the liver
3. Formation of bilirubin diglucoronide
4. Secretion of bilirubin into bile
5. Formation of urobilins in the intestine
1324
What enzyme activates fatty acid for metabolism use?
Fatty-acyl-CoA synthetase
1325
Cofactor required for fatty acid activation
Vitamin B5 or Panthotenic acid
1326
Energy required to activate fatty acid
2 ATP
1327
What is the product formed in fatty acid synthesis?
Palmitate (16:0)
1328
Where does fatty acid synthesis occur?
Cytosol
Major: Liver and lactating mammary glands
Minor: adipose tissue
1329
Substrates for fatty acid synthesis
1 acetyl CoA
7 malonyl CoA
NADPH
ATP
1330
Rate limiting step in fatty acid synthesis
Acetyl CoA + ATP -> malonyl CoA
| Enzyme: acetyl CoA carboxylase
1331
Steps in fatty acid synthesis
1. Synthesis of cytoplasmic acetyl CoA (transfer of mitochondrial acetyl CoA to cytoplasm via citrate shuttle)
2. Acetyl CoA carboxylation to malonyl CoA (via acetyl CoA carboxylase with biotin) [+ insulin, citrate]
3. Assembly of palmitate (via fatty acid synthase and Vit B5)
1332
Steps in palmitate assembly
1. Condensation
2. Reduction
3. Dehydration
4. Reduction
1333
What is the fate of Palmitate after its production?
1. Further elongation in SER and mitochondria
| 2. Desaturated in the ER (but not past the 9th carbon)
1334
Main storage form of fatty acids
Triacylglycerols
1335
Where does TAG synthesis occur?
Liver and adipose tissue
1336
Sources of glycerol-3-phosphate
1. DHAP from glycolysis (liver and adipose)
| 2. Phosphorylation of free glycerol (liver)
1337
What enzyme is responsible for the release of free fatty acids from TAGs?
Hormone sensitive lipases
1338
In the bloodstream fatty acids are always bound to?
Albumin
1339
Hormone sensitive lipases can only release what free fatty acids stored in TAG?
C1 & 3 thus resulting in
TAG -> 2 free FA and 2-mono acyl glycerol
1340
Where does B-oxidation of fatty acids occur
Mitochondria of all cells, but the fatty acid activation raft occurs in the Cytosol
Exception: RBC, kidney medulla, neurons, testes
1341
Rate limiting step in B-oxidation
Fatty acyl CoA + carnitine -> fatty acyl carnitine + CoA
| Enzyme: carnitine acyl transferase I
1342
Cutoff number of carbons that do not need a shuttle
Less than 12 carbons
1343
Steps in the carnitine shuttle
1. Fatty acyl synthase activates the fatty acid
2. Carnitine acyl transferase 1 attaches to fatty acyl to carnitine in the outer mitochondrial membrane
3. Fatty acyl-carnitine is shuttle through the inner membrane
4. Carnitine acyl transferase-2 transfers fatty acyl group back to a CoA in the mitochondrial matrix
1344
Steps in beta oxidation
1. Oxidation
2. Hydratiion
3. Oxidation
4. Thiolysis
1345
Beta oxidation of fatty acids with an odd number of carbon atoms releases?
Propionyl CoA which is converted to methylmalonyl coa (requires B12) then to succinyl CoA
1346
Which is responsible for the conversion of very long chain fatty acids?
Peroxisomes but if unsaturated it requires 3,2 enol-CoA isomerase
1347
Energy yield in ATP of beta oxidation of palmitate
129 ATP
7 NADH= 21
7 FAD= 14
8 acetyl CoA= 96
Activation = -2
1348
Intake of this compound depletes the body's NAD+ supply leading to accumulation Of fat in the liver
Alcohol
1349
Type of carnitine deficiency which leads to impaired FA oxidation and ketogenesis with hypoglycemia?
CPT-1 deficiency
1350
Type of carnitine deficiency which affects skeletal muscle and when severe the liver
CPT-2 deficiency
1351
It is a disorder school results in decreased fatty acid oxidation. Without the ATP to support gluconeogenesis, hypoglycemia becomes profound which may eventually leads to SIDS. It is prevented by frequent feeding with high carbohydrate and low fat diet.
Medium-chain fatty acyl-CoA dehydrogenase (MCAD) deficiency
1352
Associated with eating unripe fruit of the akee tree which contains hypoglycin thus activating MC and SC acyl CoA dehydrogenase
Jamaican vomiting sickness
1353
Rare neurological disorder which results to the accumulation of phytanic acid found in plant food stuff which blocks Boxidation
Refsum disease
1354
Cerebrohepatorenal syndrome resulting from the absence of peroxisomes in all tissues, it is characterized by liver dysfunction, jaundice, MR, weakness, hypotonia, and craniofacial dimorphism
Zellweger syndrome
1355
Defect in peroxismal activation of VLCFA thus leading to its accumulation. Ssx: apathy, behavral change, then visual loss spasticity, ataxia. All due to the fact since VLCFA are found in myelin tissue.
X-lied adrenoleukodystrophy
1356
Where does ketogenesis occur?
Liver mitochondria
1357
Products of ketogenesis
Acetoacetate and B-hydroxybutyrate (fuel)
| Acetone (cannot be used as fuel)
1358
Rate limiting step of ketogenesis
Acetoacetyl CoA + acetyl CoA --(HMG CoA synthase)--> HMG CoA
1359
What are the initial products that lead to the formation of acetyl CoA in ketogenolysis?
B-hydroxybutyrate -> acetoacetate -> acetyl coa
1360
What peripheral tissues can oxidize ketone bodes?
Those with mitochondria like the renal cortex, brain, and skeletal muscle
1361
Why cant liver convert acetoacetate to acetyl CoA?
It lacks succinyl-CoA acetoacetyl-CoA reductase (thiophorase)
1362
What is the Urine test for ketones? What ketone type does not it detect?
Nitroprusside test
Does not detect b-hydroxybutyrate
1363
Which part of cholesterol can a fatty acid attach to form a cholesteryl ester?
Single hydroxyl group of carbon 3 of the alpha ring
1364
Where does cholesterol synthesis occur?
All cells in the Cytosol and SER majority of which are found in the liver and intestines
1365
Substrates of cholesterol synthesis
Acetyl CoA, NADPH, ATP
1366
Rate limiting step in cholesterol synthesis
HMG CoA --(HMG CoA reductase)--> mevalonate
1367
Steps in Cholestid synthesis
1. Biosynthesis of mevalonate
2. Formation of isoprenoid units
3. Isoprene unit is formed from 6 isoprenoid units
4. Formation of lanosterol
5. Formation of cholesterol
1368
How is the cholesterol ring eliminated?
Through conversion to bile salts then secretion to bile
1369
Bile acid synthesis, found in the liver and Cytosol, rate limiting enzyme is?
Cholesterol-7-a-hydroxylase
1370
What are the primary bile acids?
Cholic acid
| Chenocholic acid
1371
What are the two amino acids used in bile acid conjugation to form bile salts?
Taurine and glycine
1372
What are the secondary bile acids?
Deoxycholic acid
| Lithocholic acid
1373
Where does steroid hormone synthesis occur?
SER of the adrenal glands, ovaries and testes, and placenta
1374
What is blocked by the drug aminogluthetimide?
The conversion of cholesterol to pregnenolone by desmolase
1375
The enzyme responsible for the breakdown of TAG to FA and:
A) 2-MAG from diet
B) FREE glycerol from chylomicrons and VLDL
C) 2-MAG from adipose
A) pancreatic lipase
B) Lipoprotein lipase
C) hormone sensitive lipase
1376
Lipoprotein with the largest percentage of TG
Chylomicrons
1377
Lipoprotein with the largest percentage of cholesteryl esters
LDL
1378
Chylomicrons transport TG and cholesterol from where to where?
Intestines to tissues
1379
VLDL transports TG from where to where?
Liver to tissues
1380
What apoprotein activates lipoprotein lipase?
APO-CII
1381
What apolipoprotein uptakes remnants by the liver?
APO E
1382
Apolipoprotein B-48 is used by chylomicrons which are created by the?
Epithelial cells
1383
What apolipoprotein is secreted by the liver for VDL?
B-100
1384
How does IDL become LDL?
By picking up cholesterol from HD!
1385
Which apoprotein delivers cholesterol into cells?
LDL
1386
Which apolipoprotein is used by HDL to activate lecithin cholesterol acyl transferase or LCAT to produce cholesterol esters?
APO-A1
1387
Difference between Type II familial hypercholesterolemia and type IV familial hypertriglyceredemia?
The former has high LDL leader to xanthomas and xanthelasmas with increased risk of atherosclerosis and CHD
The latter has increased VLDL production leading to a triad of
1. DM type 2
2. CAD
3. Obesity
1388
Phospholipid is composed of
DAG
Alcohol
Phosphodiester bond
1389
Most abundant phospholipid which is important in nervous transmission
Phosphatidylcholine
1390
Phospholipid playing a role in apoptosis
Phosphatidyl serine
1391
Phospholipid that is a major component of surfactant?
Dipalmitoylphosphatidylcholine
1392
Phospholipid reservoir for arachidonic acid in the membranes
Phosphatidylinositol
1393
What phospholipid is essential in mitochondrial function which is also used as a non-troponemal test due to its ability to act as an antigen?
Cardiolipin
1394
```
Composition of these glycolipids:
Ceramide
Cerebroside
Globoside
Ganglioside
Sulfatide
```
Ceramide: sphingosine + FA
```
Ceramide + ________
Glucose or galactose = Cerebroside
Oligosacchardide = Globoside
N-acetylneuramic acid = Ganglioside
Sulfated galactose = Sulfatide
```
1395
Hexosaminidase a ficiency leading to Ssx like cherry red macula, MR, hypotonia
Tay-Sachs disease
1396
A-galactosidase deficiency leading to 3Rs: recessive x-linked, rash, renal failure
Fabrys disease
1397
B-glucosidase deficiency leading to hepatosplenomegaly and erosion of long bones
Gauchers dissease
1398
Sphingomyelinase deficiency leading to hepatosplenomegaly
Nieman-pick disease
1399
The set of all proteins expressed by an individual at a particular time
Proteome
1400
Aims to identify the entire complement of proteins elaborated by a cell under diverse conditions
Proteomics
1401
What amino acid is needed to form ALA in heme synthesis?
Glycine combined with succinyl CoA
1402
Which amino acid carries nitrogen from the liver?
Alanine
1403
Which amino acids are implicated in maple syrup disease
valine, lucine, isoleucine
1404
What enzyme is responsible for the buildup of phenyl lactate, phenyl acetate, and phenylpyruvate?
Phenylalanine hydroxylase
1405
What amino acid is the precursor for niacin, serotonin, and melatonin?
Serotonin
1406
What is the amino acid precursor for homocysteine?
Methionine
1407
What amino acid contributes to the fibrous structure of collagen and interrupts a-helices in globular proteins?
Proline
1408
Increase of the combination of this Amino acid is responsible for the curly hair of people?
Cysteine + cysteine = cystine
1409
Amino acids with sites for O-linked glycosylation in the Golgi apparatus?
Serine and threonine
1410
Site for n-linked glycosylation in the ER
Asparagine
1411
Amino acid deaminated by an enzyme which results in the formation of ammonia. This is the major carrier of nitrogen to the liver from peripheral tissues,
Glutaminase deaminates glutamine
1412
Amino acid used in the determination for Folic acid deficiency. What is the test called?
Histidine used in the N-forminoglutamate excretion test
| Increased amounts of FIGu in urine by Folic acid deficient individuals after histindine intake
1413
Precursor amino acid for creatinine, urea, nitric oxide
Arginine
1414
Essential amino acids that cannot be synthesized by the body and must come from the diet
PVT TIM HALL always ARGues and never TYRes
Phenylalanine, valine, tryptophan, threonine' isoleucine, methionine, histidine, argenine, Leucine, Lysine
1415
Heme is a complex of?
Protoporphorin IX and heme
1416
What is the Bohr effect?
HBO2 + H+ HbH + O2
1417
What is an oxidized for of HB (Fe 3+) that does not bind O2 readily which could lead to chocolate cyanosis ? It is treated with oral methylene blue or ascorbic acid up to IV methylene blue.
Methemoglobin
1418
Hemoglobin bound to carbon monoxide instead of O2 leading to a cherry pink color.
Carboxyhemoglobin
1419
HB bound to carbon dioxide is called
Carbaminohenoglobin
1420
Classification of alpha and beta thalassemia
Alpha: silent carrier, a-thalassemia trait, Hb H disease, hydrops fetalis
Beta: B-thalassemia minor and major
1421
Most frequently affected collagen in Ehler Danlos syndrome leading to hyper extensible skin, tendency to bleed, hyper mobile joints, and increased risk for berry aneurysms.
Collagen type 3
1422
Collagen I mutation leading to bendable and easily fractured bones. Accompanied with blue sclerae, hearing loss, and dental imperfections.
Osteogenesis imperfecta
1423
Vitamin C deficiency leading to decreased hydroxylation of collagen. This leads to sore spongy gums, loose teeth, poor wound healing, and petecchiae on skin and mucous membranes.
Scurvy
1424
Type IV collagen defect leading to hematuria and ESRD
Alpert syndrome
1425
Collagen defect leading to kinky hair due to a deficiency of copper required by lysyl oxidase to strengthen collagen fibers.
Menke syndrome
1426
Skin breaking and blisters as a result for minor trauma. This disease is due to a defect in collage VII.
Epidermolysis bullosa
1427
Like collagen elastin has pro line and Lysine but has little and no?
Hydroxyproline
| Hydroxylysine
1428
Protein degradation mechanisms of nitrogen
Energy dependent ubiquitin-proteosome mechanism
| Non-energy dependent degradation enzyme
1429
Phases in amino acid catabolism
First phase: removal of a-amino group forming ammonia and a corresponding ketoacid
Second phase: carbon skeletons of a-ketoacids are converted to common intermediates of energy producing metabolic pathwas
1430
Two main steps in nitrogen removal from AA
1. Transamination
| 2. Oxidative deamination
1431
Where does transamination occur?
All cells of the body
1432
All but two amino acids transfer their amino groups to a-ketoglutarate except?
Lysine and threonine
1433
What is the coenzyme for the two aminotransferases?
Pyridoxal phosphate (vitamin B6)
1434
Oxidative deamination occurs where and for which amino acid only?
Liver and kidney
| Only glutamate
1435
Glutamate is oxidized by glutamate dehydrogenases and deaminated to form ?
free ammonia which is used to make urea
1436
What does the conversion of glutamate to a-ketoglutarate yield? What about vice versa?
Glutamate -> a ketoglutarate NH3 + NADH
| A ketoglutarate -> glutamate NADP+ + NH3
1437
How is excess nitrogen removal from peripheral tissues removed?
1. Glutamine: via glutamate + ammonia (through Flutamide synthaetase)
2. Alanine: via glucose -> pyruvate + glutamate -> alanine cycle
1438
Glutaminase deaminates glutamine to produce ammonium ion which is excreted from the body. Where are the two tissues this enzyme could be located?
Kidneys and small intestines
1439
Another name for urea cycle
Ornithine cycle or krebs-henseleit cycle
1440
What are the donors of the urea molecule?
1. NH3 from free ammonia
2. NH3 from aspartate
3. 1C and 1O from CO2
1441
Reactions in the urea cycle
1. Formation of carbamoyl phosphate (via carbamoyl phosphate synthetase I)
2. Formation of citrulline (via Ornithine transcarbamoylase)
3. Synthesis of arginosuccinate (arginosuccinate synthetase)
4. Cleavage of arginosuccinate to form arginine (Arginosuccinase)
5. Arginine cleavage to yield urea and Ornithine (arginase)
1442
Rate limiting step of urea cycle
Carbamoyl phosphate synthetase I
1443
Energy requirement of urea cycle
4 ATP
1444
Co factors of urea cycle
N-acetylglutamate
| Biotin
1445
Hereditary hyperammonemia produces symptoms such as
Hyperammonemia, elevated blood glutamine, decreased BUN
| Parents with lethargy, vomiting, hyperventilation, convulsions, cerebral edema, coma, and death
1446
Treatment for hereditary hyperammonemia
Low protein diet
| Administration of sodium benzoate or phenylpyruvate to capture and excrete excess nitrogen
1447
Ketogenic carbon skeletons of AA
Leucine
Lysine
Yields acetoacetate or acetyl-coa/ acetoacetyl-coa
1448
Ketogenic and glucogenic carbon skeletons of AA
```
WIFY
Phenylalanine
Isoleucine
Tryptophan
Tyrosine
```
Yields Ketogenic and glucose or glycogen by products
1449
This amino acid acts as a raw material in the biosynthesis of Heme, purines, creatine
Glycine
1450
This amino acid acts as a raw material in the biosynthesis of phospholipid, sphingolipid, purines, thymine
Serine
1451
This amino acid acts as a raw material in the biosynthesis of GABA
Glutamate
1452
This amino acid acts as a raw material in the biosynthesis of creatine, polyamines, nitric oxide
Arginine
1453
This amino acid acts as a raw material in the biosynthesis of serotonin, NAD+, NADP+, melatonin
Tryptophan
1454
This amino acid acts as a raw material in the biosynthesis of catecholamines, thyroid hormones, melanin
Tyrosine
1455
3 hormones dependent on tyrosine
Thyroid hormones
Melanin
Catecholamines
1456
Deficiency of homogenistic acid oxidase in the degrative pathway of tyrosine which results in urine turning to black on standing with dark connective tissues (ochronosis)
Alkaptonuria
1457
Congenital deficiency due tyrosinase deficieny or defective tyrosine transporters which leads to an increased risk for skin cancer.
Albinism
1458
Autosomal recessive disorder that may either be due to decreased methionine, increased cysteine, B6, and folate or decreased affinity for cystathione synthase. This results in mental retardation, osteoporosis, tall stature, lens subluxation, and atherosclerosis.
Homocystinuria
1459
Common inherited defect of renal tubular amino acid transporter for its parent compound, Ornithine, Lysine, and arginine, in the PCT of the kidneys. It eventually precipitates and cause staghorn caliculi. What is its treatment?
Cystinuria is treated with acetazolamide to alkalinize the urine
1460
The initial and last three steps of heme synthesis occurs in?
The mitochondria
1461
Heme synthesis summary
1. Formation of ALA (via ALA synthase and B6)
2. Formation of porphobilinogen
3. Formation of uroporphyrinogen
4. Formation of heme
1462
Lead inhibits what two steps in heme synthesis?
1. Introduction of Fe 2+ into protoporphyrin IX via ferrochelatase
2. Condensation of two ALA molecules by zinc containing ALA dehydratase
1463
Where is B6 a cofactors of?
1. Heme synthesis
2. Synthesis of cystathionine from homocysteine
3. Transamination between alanine and a-ketoglutarate
1464
Most common porphyria
Porphyria cutanea tarda
1465
Which part of heme synthesis do these symptoms appear?
1. Photosensitivity
2. Neuropsychiatric symptoms
1. After ring formation
| 2. Before ring formation
1466
Pyridoxine ficiency associated with isoniazid therapy results in this histopathologic finding
Sideroblastic anemia with ringed sideroblast
1467
Poisoning due to this heavy metal leads to coar basophilic stippling of RBC, peripheral neuropathy, lines in gums, increas in urinary ALA and free erythrocytes porphorin
lead poisoning
1468
Microcytic hypo chromic anemia is found in
IDA
Thalassemia
Lead poisoning
1469
Megaloblastic anemia is found in
Folate or B12 deficiency
| Pernicious anemia
1470
Normoyctic normochromic anemia is found in
Anemia of chronic kidney disease
| Blood loss
1471
Increase in MCHC is found in
Hereditary spherocytosis
1472
Summary of heme degradation
1. Formation of bilirubin
2. Uptake of bilirubin by the liver
3. Formation of bilirubin diglucoronide
4. Secretion of bilirubin into bile
5. Formation of urobilins in the intestine
1473
Colors of biliverdin, bilirubin, urobilinogen, stercolin, urobilin
```
Biliverdin: green
Bilirubin: red orange
Urobilinogen: colorless
Stercolin: brown orange red
Urobilin: yellow
```
1474
Examples of unconjugated hyperbilirubinemia
```
Hemolytic anemia
Physiologic jaundice
Crigler-najjar syndrome types I and II
Gilbert syndrome
Toxic hyperbilirubinemia
```
1475
Examples of conjugated hyperbilirubinemia
Biliary tree obstruction
Dubin-Johnson syndrome
Rotor syndrome
1476
What reaction measures total and direct bilirubin?
Van den bergs reaction
1477
What enzyme activates fatty acid for metabolism use?
Fatty-acyl-CoA synthetase
1478
Cofactor required for fatty acid activation
Vitamin B5 or Panthotenic acid
1479
Energy required to activate fatty acid
2 ATP
1480
What is the product formed in fatty acid synthesis?
Palmitate (16:0)
1481
Where does fatty acid synthesis occur?
Cytosol
Major: Liver and lactating mammary glands
Minor: adipose tissue
1482
Substrates for fatty acid synthesis
1 acetyl CoA
7 malonyl CoA
NADPH
ATP
1483
Rate limiting step in fatty acid synthesis
Acetyl CoA + ATP -> malonyl CoA
| Enzyme: acetyl CoA carboxylase
1484
Steps in fatty acid synthesis
1. Synthesis of cytoplasmic acetyl CoA (transfer of mitochondrial acetyl CoA to cytoplasm via citrate shuttle)
2. Acetyl CoA carboxylation to malonyl CoA (via acetyl CoA carboxylase with biotin) [+ insulin, citrate]
3. Assembly of palmitate (via fatty acid synthase and Vit B5)
1485
Steps in palmitate assembly
1. Condensation
2. Reduction
3. Dehydration
4. Reduction
1486
What is the fate of Palmitate after its production?
1. Further elongation in SER and mitochondria
| 2. Desaturated in the ER (but not past the 9th carbon)
1487
Main storage form of fatty acids
Triacylglycerols
1488
Where does TAG synthesis occur?
Liver and adipose tissue
1489
Sources of glycerol-3-phosphate
1. DHAP from glycolysis (liver and adipose)
| 2. Phosphorylation of free glycerol (liver)
1490
What enzyme is responsible for the release of free fatty acids from TAGs?
Hormone sensitive lipases
1491
In the bloodstream fatty acids are always bound to?
Albumin
1492
Hormone sensitive lipases can only release what free fatty acids stored in TAG?
C1 & 3 thus resulting in
TAG -> 2 free FA and 2-mono acyl glycerol
1493
Where does B-oxidation of fatty acids occur
Mitochondria of all cells, but the fatty acid activation raft occurs in the Cytosol
Exception: RBC, kidney medulla, neurons, testes
1494
Rate limiting step in B-oxidation
Fatty acyl CoA + carnitine -> fatty acyl carnitine + CoA
| Enzyme: carnitine acyl transferase I
1495
Cutoff number of carbons that do not need a shuttle
Less than 12 carbons
1496
Steps in the carnitine shuttle
1. Fatty acyl synthase activates the fatty acid
2. Carnitine acyl transferase 1 attaches to fatty acyl to carnitine in the outer mitochondrial membrane
3. Fatty acyl-carnitine is shuttle through the inner membrane
4. Carnitine acyl transferase-2 transfers fatty acyl group back to a CoA in the mitochondrial matrix
1497
Steps in beta oxidation
1. Oxidation
2. Hydratiion
3. Oxidation
4. Thiolysis
1498
Beta oxidation of fatty acids with an odd number of carbon atoms releases?
Propionyl CoA which is converted to methylmalonyl coa (requires B12) then to succinyl CoA
1499
Which is responsible for the conversion of very long chain fatty acids?
Peroxisomes but if unsaturated it requires 3,2 enol-CoA isomerase
1500
Energy yield in ATP of beta oxidation of palmitate
129 ATP
7 NADH= 21
7 FAD= 14
8 acetyl CoA= 96
Activation = -2
1501
Intake of this compound depletes the body's NAD+ supply leading to accumulation Of fat in the liver
Alcohol
1502
Type of carnitine deficiency which leads to impaired FA oxidation and ketogenesis with hypoglycemia?
CPT-1 deficiency
1503
Type of carnitine deficiency which affects skeletal muscle and when severe the liver
CPT-2 deficiency
1504
It is a disorder school results in decreased fatty acid oxidation. Without the ATP to support gluconeogenesis, hypoglycemia becomes profound which may eventually leads to SIDS. It is prevented by frequent feeding with high carbohydrate and low fat diet.
Medium-chain fatty acyl-CoA dehydrogenase (MCAD) deficiency
1505
Associated with eating unripe fruit of the akee tree which contains hypoglycin thus activating MC and SC acyl CoA dehydrogenase
Jamaican vomiting sickness
1506
Rare neurological disorder which results to the accumulation of phytanic acid found in plant food stuff which blocks Boxidation
Refsum disease
1507
Cerebrohepatorenal syndrome resulting from the absence of peroxisomes in all tissues, it is characterized by liver dysfunction, jaundice, MR, weakness, hypotonia, and craniofacial dimorphism
Zellweger syndrome
1508
Defect in peroxismal activation of VLCFA thus leading to its accumulation. Ssx: apathy, behavral change, then visual loss spasticity, ataxia. All due to the fact since VLCFA are found in myelin tissue.
X-lied adrenoleukodystrophy
1509
Where does ketogenesis occur?
Liver mitochondria
1510
Products of ketogenesis
Acetoacetate and B-hydroxybutyrate (fuel)
| Acetone (cannot be used as fuel)
1511
Rate limiting step of ketogenesis
Acetoacetyl CoA + acetyl CoA --(HMG CoA synthase)--> HMG CoA
1512
What are the initial products that lead to the formation of acetyl CoA in ketogenolysis?
B-hydroxybutyrate -> acetoacetate -> acetyl coa
1513
What peripheral tissues can oxidize ketone bodes?
Those with mitochondria like the renal cortex, brain, and skeletal muscle
1514
Why cant liver convert acetoacetate to acetyl CoA?
It lacks succinyl-CoA acetoacetyl-CoA reductase (thiophorase)
1515
What is the Urine test for ketones? What ketone type does not it detect?
Nitroprusside test
Does not detect b-hydroxybutyrate
1516
Which part of cholesterol can a fatty acid attach to form a cholesteryl ester?
Single hydroxyl group of carbon 3 of the alpha ring
1517
Where does cholesterol synthesis occur?
All cells in the Cytosol and SER majority of which are found in the liver and intestines
1518
Substrates of cholesterol synthesis
Acetyl CoA, NADPH, ATP
1519
Rate limiting step in cholesterol synthesis
HMG CoA --(HMG CoA reductase)--> mevalonate
1520
Steps in Cholestid synthesis
1. Biosynthesis of mevalonate
2. Formation of isoprenoid units
3. Isoprene unit is formed from 6 isoprenoid units
4. Formation of lanosterol
5. Formation of cholesterol
1521
How is the cholesterol ring eliminated?
Through conversion to bile salts then secretion to bile
1522
Bile acid synthesis, found in the liver and Cytosol, rate limiting enzyme is?
Cholesterol-7-a-hydroxylase
1523
What are the primary bile acids?
Cholic acid
| Chenocholic acid
1524
What are the two amino acids used in bile acid conjugation to form bile salts?
Taurine and glycine
1525
What are the secondary bile acids?
Deoxycholic acid
| Lithocholic acid
1526
Where does steroid hormone synthesis occur?
SER of the adrenal glands, ovaries and testes, and placenta
1527
What is blocked by the drug aminogluthetimide?
The conversion of cholesterol to pregnenolone by desmolase
1528
The enzyme responsible for the breakdown of TAG to FA and:
A) 2-MAG from diet
B) FREE glycerol from chylomicrons and VLDL
C) 2-MAG from adipose
A) pancreatic lipase
B) Lipoprotein lipase
C) hormone sensitive lipase
1529
Lipoprotein with the largest percentage of TG
Chylomicrons
1530
Lipoprotein with the largest percentage of cholesteryl esters
LDL
1531
Chylomicrons transport TG and cholesterol from where to where?
Intestines to tissues
1532
VLDL transports TG from where to where?
Liver to tissues
1533
What apoprotein activates lipoprotein lipase?
APO-CII
1534
What apolipoprotein uptakes remnants by the liver?
APO E
1535
Apolipoprotein B-48 is used by chylomicrons which are created by the?
Epithelial cells
1536
What apolipoprotein is secreted by the liver for VDL?
B-100
1537
How does IDL become LDL?
By picking up cholesterol from HD!
1538
Which apoprotein delivers cholesterol into cells?
LDL
1539
Which apolipoprotein is used by HDL to activate lecithin cholesterol acyl transferase or LCAT to produce cholesterol esters?
APO-A1
1540
Difference between Type II familial hypercholesterolemia and type IV familial hypertriglyceredemia?
The former has high LDL leader to xanthomas and xanthelasmas with increased risk of atherosclerosis and CHD
The latter has increased VLDL production leading to a triad of
1. DM type 2
2. CAD
3. Obesity
1541
Phospholipid is composed of
DAG
Alcohol
Phosphodiester bond
1542
Most abundant phospholipid which is important in nervous transmission
Phosphatidylcholine
1543
Phospholipid playing a role in apoptosis
Phosphatidyl serine
1544
Phospholipid that is a major component of surfactant?
Dipalmitoylphosphatidylcholine
1545
Phospholipid reservoir for arachidonic acid in the membranes
Phosphatidylinositol
1546
What phospholipid is essential in mitochondrial function which is also used as a non-troponemal test due to its ability to act as an antigen?
Cardiolipin
1547
```
Composition of these glycolipids:
Ceramide
Cerebroside
Globoside
Ganglioside
Sulfatide
```
Ceramide: sphingosine + FA
```
Ceramide + ________
Glucose or galactose = Cerebroside
Oligosacchardide = Globoside
N-acetylneuramic acid = Ganglioside
Sulfated galactose = Sulfatide
```
1548
Hexosaminidase a ficiency leading to Ssx like cherry red macula, MR, hypotonia
Tay-Sachs disease
1549
A-galactosidase deficiency leading to 3Rs: recessive x-linked, rash, renal failure
Fabrys disease
1550
B-glucosidase deficiency leading to hepatosplenomegaly and erosion of long bones
Gauchers dissease
1551
Sphingomyelinase deficiency leading to hepatosplenomegaly
Nieman-pick disease
1552
The set of all proteins expressed by an individual at a particular time
Proteome
1553
Aims to identify the entire complement of proteins elaborated by a cell under diverse conditions
Proteomics
1554
What amino acid is needed to form ALA in heme synthesis?
Glycine combined with succinyl CoA
1555
Which amino acid carries nitrogen from the liver?
Alanine
1556
Which amino acids are implicated in maple syrup disease
valine, lucine, isoleucine
1557
What enzyme is responsible for the buildup of phenyl lactate, phenyl acetate, and phenylpyruvate?
Phenylalanine hydroxylase
1558
What amino acid is the precursor for niacin, serotonin, and melatonin?
Serotonin
1559
What is the amino acid precursor for homocysteine?
Methionine
1560
What amino acid contributes to the fibrous structure of collagen and interrupts a-helices in globular proteins?
Proline
1561
Increase of the combination of this Amino acid is responsible for the curly hair of people?
Cysteine + cysteine = cystine
1562
Amino acids with sites for O-linked glycosylation in the Golgi apparatus?
Serine and threonine
1563
Site for n-linked glycosylation in the ER
Asparagine
1564
Amino acid deaminated by an enzyme which results in the formation of ammonia. This is the major carrier of nitrogen to the liver from peripheral tissues,
Glutaminase deaminates glutamine
1565
Amino acid used in the determination for Folic acid deficiency. What is the test called?
Histidine used in the N-forminoglutamate excretion test
| Increased amounts of FIGu in urine by Folic acid deficient individuals after histindine intake
1566
Precursor amino acid for creatinine, urea, nitric oxide
Arginine
1567
Essential amino acids that cannot be synthesized by the body and must come from the diet
PVT TIM HALL always ARGues and never TYRes
Phenylalanine, valine, tryptophan, threonine' isoleucine, methionine, histidine, argenine, Leucine, Lysine
1568
Heme is a complex of?
Protoporphorin IX and heme
1569
What is the Bohr effect?
HBO2 + H+ HbH + O2
1570
What is an oxidized for of HB (Fe 3+) that does not bind O2 readily which could lead to chocolate cyanosis ? It is treated with oral methylene blue or ascorbic acid up to IV methylene blue.
Methemoglobin
1571
Hemoglobin bound to carbon monoxide instead of O2 leading to a cherry pink color.
Carboxyhemoglobin
1572
HB bound to carbon dioxide is called
Carbaminohenoglobin
1573
Classification of alpha and beta thalassemia
Alpha: silent carrier, a-thalassemia trait, Hb H disease, hydrops fetalis
Beta: B-thalassemia minor and major
1574
Most frequently affected collagen in Ehler Danlos syndrome leading to hyper extensible skin, tendency to bleed, hyper mobile joints, and increased risk for berry aneurysms.
Collagen type 3
1575
Collagen I mutation leading to bendable and easily fractured bones. Accompanied with blue sclerae, hearing loss, and dental imperfections.
Osteogenesis imperfecta
1576
Vitamin C deficiency leading to decreased hydroxylation of collagen. This leads to sore spongy gums, loose teeth, poor wound healing, and petecchiae on skin and mucous membranes.
Scurvy
1577
Type IV collagen defect leading to hematuria and ESRD
Alpert syndrome
1578
Collagen defect leading to kinky hair due to a deficiency of copper required by lysyl oxidase to strengthen collagen fibers.
Menke syndrome
1579
Skin breaking and blisters as a result for minor trauma. This disease is due to a defect in collage VII.
Epidermolysis bullosa
1580
Like collagen elastin has pro line and Lysine but has little and no?
Hydroxyproline
| Hydroxylysine
1581
Protein degradation mechanisms of nitrogen
Energy dependent ubiquitin-proteosome mechanism
| Non-energy dependent degradation enzyme
1582
Phases in amino acid catabolism
First phase: removal of a-amino group forming ammonia and a corresponding ketoacid
Second phase: carbon skeletons of a-ketoacids are converted to common intermediates of energy producing metabolic pathwas
1583
Two main steps in nitrogen removal from AA
1. Transamination
| 2. Oxidative deamination
1584
Where does transamination occur?
All cells of the body
1585
All but two amino acids transfer their amino groups to a-ketoglutarate except?
Lysine and threonine
1586
What is the coenzyme for the two aminotransferases?
Pyridoxal phosphate (vitamin B6)
1587
Oxidative deamination occurs where and for which amino acid only?
Liver and kidney
| Only glutamate
1588
Glutamate is oxidized by glutamate dehydrogenases and deaminated to form ?
free ammonia which is used to make urea
1589
What does the conversion of glutamate to a-ketoglutarate yield? What about vice versa?
Glutamate -> a ketoglutarate NH3 + NADH
| A ketoglutarate -> glutamate NADP+ + NH3
1590
How is excess nitrogen removal from peripheral tissues removed?
1. Glutamine: via glutamate + ammonia (through Flutamide synthaetase)
2. Alanine: via glucose -> pyruvate + glutamate -> alanine cycle
1591
Glutaminase deaminates glutamine to produce ammonium ion which is excreted from the body. Where are the two tissues this enzyme could be located?
Kidneys and small intestines
1592
Another name for urea cycle
Ornithine cycle or krebs-henseleit cycle
1593
What are the donors of the urea molecule?
1. NH3 from free ammonia
2. NH3 from aspartate
3. 1C and 1O from CO2
1594
Reactions in the urea cycle
1. Formation of carbamoyl phosphate (via carbamoyl phosphate synthetase I)
2. Formation of citrulline (via Ornithine transcarbamoylase)
3. Synthesis of arginosuccinate (arginosuccinate synthetase)
4. Cleavage of arginosuccinate to form arginine (Arginosuccinase)
5. Arginine cleavage to yield urea and Ornithine (arginase)
1595
Rate limiting step of urea cycle
Carbamoyl phosphate synthetase I
1596
Energy requirement of urea cycle
4 ATP
1597
Co factors of urea cycle
N-acetylglutamate
| Biotin
1598
Hereditary hyperammonemia produces symptoms such as
Hyperammonemia, elevated blood glutamine, decreased BUN
| Parents with lethargy, vomiting, hyperventilation, convulsions, cerebral edema, coma, and death
1599
Treatment for hereditary hyperammonemia
Low protein diet
| Administration of sodium benzoate or phenylpyruvate to capture and excrete excess nitrogen
1600
Ketogenic carbon skeletons of AA
Leucine
Lysine
Yields acetoacetate or acetyl-coa/ acetoacetyl-coa
1601
Ketogenic and glucogenic carbon skeletons of AA
```
WIFY
Phenylalanine
Isoleucine
Tryptophan
Tyrosine
```
Yields Ketogenic and glucose or glycogen by products
1602
This amino acid acts as a raw material in the biosynthesis of Heme, purines, creatine
Glycine
1603
This amino acid acts as a raw material in the biosynthesis of phospholipid, sphingolipid, purines, thymine
Serine
1604
This amino acid acts as a raw material in the biosynthesis of GABA
Glutamate
1605
This amino acid acts as a raw material in the biosynthesis of creatine, polyamines, nitric oxide
Arginine
1606
This amino acid acts as a raw material in the biosynthesis of serotonin, NAD+, NADP+, melatonin
Tryptophan
1607
This amino acid acts as a raw material in the biosynthesis of catecholamines, thyroid hormones, melanin
Tyrosine
1608
3 hormones dependent on tyrosine
Thyroid hormones
Melanin
Catecholamines
1609
Deficiency of homogenistic acid oxidase in the degrative pathway of tyrosine which results in urine turning to black on standing with dark connective tissues (ochronosis)
Alkaptonuria
1610
Congenital deficiency due tyrosinase deficieny or defective tyrosine transporters which leads to an increased risk for skin cancer.
Albinism
1611
Autosomal recessive disorder that may either be due to decreased methionine, increased cysteine, B6, and folate or decreased affinity for cystathione synthase. This results in mental retardation, osteoporosis, tall stature, lens subluxation, and atherosclerosis.
Homocystinuria
1612
Common inherited defect of renal tubular amino acid transporter for its parent compound, Ornithine, Lysine, and arginine, in the PCT of the kidneys. It eventually precipitates and cause staghorn caliculi. What is its treatment?
Cystinuria is treated with acetazolamide to alkalinize the urine
1613
The initial and last three steps of heme synthesis occurs in?
The mitochondria
1614
Heme synthesis summary
1. Formation of ALA (via ALA synthase and B6)
2. Formation of porphobilinogen
3. Formation of uroporphyrinogen
4. Formation of heme
1615
Lead inhibits what two steps in heme synthesis?
1. Introduction of Fe 2+ into protoporphyrin IX via ferrochelatase
2. Condensation of two ALA molecules by zinc containing ALA dehydratase
1616
Where is B6 a cofactors of?
1. Heme synthesis
2. Synthesis of cystathionine from homocysteine
3. Transamination between alanine and a-ketoglutarate
1617
Most common porphyria
Porphyria cutanea tarda
1618
Which part of heme synthesis do these symptoms appear?
1. Photosensitivity
2. Neuropsychiatric symptoms
1. After ring formation
| 2. Before ring formation
1619
Pyridoxine ficiency associated with isoniazid therapy results in this histopathologic finding
Sideroblastic anemia with ringed sideroblast
1620
Poisoning due to this heavy metal leads to coar basophilic stippling of RBC, peripheral neuropathy, lines in gums, increas in urinary ALA and free erythrocytes porphorin
lead poisoning
1621
Microcytic hypo chromic anemia is found in
IDA
Thalassemia
Lead poisoning
1622
Megaloblastic anemia is found in
Folate or B12 deficiency
| Pernicious anemia
1623
Normoyctic normochromic anemia is found in
Anemia of chronic kidney disease
| Blood loss
1624
Increase in MCHC is found in
Hereditary spherocytosis
1625
Summary of heme degradation
1. Formation of bilirubin
2. Uptake of bilirubin by the liver
3. Formation of bilirubin diglucoronide
4. Secretion of bilirubin into bile
5. Formation of urobilins in the intestine
1626
Colors of biliverdin, bilirubin, urobilinogen, stercolin, urobilin
```
Biliverdin: green
Bilirubin: red orange
Urobilinogen: colorless
Stercolin: brown orange red
Urobilin: yellow
```
1627
Examples of unconjugated hyperbilirubinemia
```
Hemolytic anemia
Physiologic jaundice
Crigler-najjar syndrome types I and II
Gilbert syndrome
Toxic hyperbilirubinemia
```
1628
Examples of conjugated hyperbilirubinemia
Biliary tree obstruction
Dubin-Johnson syndrome
Rotor syndrome
1629
What reaction measures total and direct bilirubin?
Van den bergs reaction
1630
What enzyme activates fatty acid for metabolism use?
Fatty-acyl-CoA synthetase
1631
Cofactor required for fatty acid activation
Vitamin B5 or Panthotenic acid
1632
Energy required to activate fatty acid
2 ATP
1633
What is the product formed in fatty acid synthesis?
Palmitate (16:0)
1634
Where does fatty acid synthesis occur?
Cytosol
Major: Liver and lactating mammary glands
Minor: adipose tissue
1635
Substrates for fatty acid synthesis
1 acetyl CoA
7 malonyl CoA
NADPH
ATP
1636
Rate limiting step in fatty acid synthesis
Acetyl CoA + ATP -> malonyl CoA
| Enzyme: acetyl CoA carboxylase
1637
Steps in fatty acid synthesis
1. Synthesis of cytoplasmic acetyl CoA (transfer of mitochondrial acetyl CoA to cytoplasm via citrate shuttle)
2. Acetyl CoA carboxylation to malonyl CoA (via acetyl CoA carboxylase with biotin) [+ insulin, citrate]
3. Assembly of palmitate (via fatty acid synthase and Vit B5)
1638
Steps in palmitate assembly
1. Condensation
2. Reduction
3. Dehydration
4. Reduction
1639
What is the fate of Palmitate after its production?
1. Further elongation in SER and mitochondria
| 2. Desaturated in the ER (but not past the 9th carbon)
1640
Main storage form of fatty acids
Triacylglycerols
1641
Where does TAG synthesis occur?
Liver and adipose tissue
1642
Sources of glycerol-3-phosphate
1. DHAP from glycolysis (liver and adipose)
| 2. Phosphorylation of free glycerol (liver)
1643
What enzyme is responsible for the release of free fatty acids from TAGs?
Hormone sensitive lipases
1644
In the bloodstream fatty acids are always bound to?
Albumin
1645
Hormone sensitive lipases can only release what free fatty acids stored in TAG?
C1 & 3 thus resulting in
TAG -> 2 free FA and 2-mono acyl glycerol
1646
Where does B-oxidation of fatty acids occur
Mitochondria of all cells, but the fatty acid activation raft occurs in the Cytosol
Exception: RBC, kidney medulla, neurons, testes
1647
Rate limiting step in B-oxidation
Fatty acyl CoA + carnitine -> fatty acyl carnitine + CoA
| Enzyme: carnitine acyl transferase I
1648
Cutoff number of carbons that do not need a shuttle
Less than 12 carbons
1649
Steps in the carnitine shuttle
1. Fatty acyl synthase activates the fatty acid
2. Carnitine acyl transferase 1 attaches to fatty acyl to carnitine in the outer mitochondrial membrane
3. Fatty acyl-carnitine is shuttle through the inner membrane
4. Carnitine acyl transferase-2 transfers fatty acyl group back to a CoA in the mitochondrial matrix
1650
Steps in beta oxidation
1. Oxidation
2. Hydratiion
3. Oxidation
4. Thiolysis
1651
Beta oxidation of fatty acids with an odd number of carbon atoms releases?
Propionyl CoA which is converted to methylmalonyl coa (requires B12) then to succinyl CoA
1652
Which is responsible for the conversion of very long chain fatty acids?
Peroxisomes but if unsaturated it requires 3,2 enol-CoA isomerase
1653
Energy yield in ATP of beta oxidation of palmitate
129 ATP
7 NADH= 21
7 FAD= 14
8 acetyl CoA= 96
Activation = -2
1654
Intake of this compound depletes the body's NAD+ supply leading to accumulation Of fat in the liver
Alcohol
1655
Type of carnitine deficiency which leads to impaired FA oxidation and ketogenesis with hypoglycemia?
CPT-1 deficiency
1656
Type of carnitine deficiency which affects skeletal muscle and when severe the liver
CPT-2 deficiency
1657
It is a disorder school results in decreased fatty acid oxidation. Without the ATP to support gluconeogenesis, hypoglycemia becomes profound which may eventually leads to SIDS. It is prevented by frequent feeding with high carbohydrate and low fat diet.
Medium-chain fatty acyl-CoA dehydrogenase (MCAD) deficiency
1658
Associated with eating unripe fruit of the akee tree which contains hypoglycin thus activating MC and SC acyl CoA dehydrogenase
Jamaican vomiting sickness
1659
Rare neurological disorder which results to the accumulation of phytanic acid found in plant food stuff which blocks Boxidation
Refsum disease
1660
Cerebrohepatorenal syndrome resulting from the absence of peroxisomes in all tissues, it is characterized by liver dysfunction, jaundice, MR, weakness, hypotonia, and craniofacial dimorphism
Zellweger syndrome
1661
Defect in peroxismal activation of VLCFA thus leading to its accumulation. Ssx: apathy, behavral change, then visual loss spasticity, ataxia. All due to the fact since VLCFA are found in myelin tissue.
X-lied adrenoleukodystrophy
1662
Where does ketogenesis occur?
Liver mitochondria
1663
Products of ketogenesis
Acetoacetate and B-hydroxybutyrate (fuel)
| Acetone (cannot be used as fuel)
1664
Rate limiting step of ketogenesis
Acetoacetyl CoA + acetyl CoA --(HMG CoA synthase)--> HMG CoA
1665
What are the initial products that lead to the formation of acetyl CoA in ketogenolysis?
B-hydroxybutyrate -> acetoacetate -> acetyl coa
1666
What peripheral tissues can oxidize ketone bodes?
Those with mitochondria like the renal cortex, brain, and skeletal muscle
1667
Why cant liver convert acetoacetate to acetyl CoA?
It lacks succinyl-CoA acetoacetyl-CoA reductase (thiophorase)
1668
What is the Urine test for ketones? What ketone type does not it detect?
Nitroprusside test
Does not detect b-hydroxybutyrate
1669
Which part of cholesterol can a fatty acid attach to form a cholesteryl ester?
Single hydroxyl group of carbon 3 of the alpha ring
1670
Where does cholesterol synthesis occur?
All cells in the Cytosol and SER majority of which are found in the liver and intestines
1671
Substrates of cholesterol synthesis
Acetyl CoA, NADPH, ATP
1672
Rate limiting step in cholesterol synthesis
HMG CoA --(HMG CoA reductase)--> mevalonate
1673
Steps in Cholestid synthesis
1. Biosynthesis of mevalonate
2. Formation of isoprenoid units
3. Isoprene unit is formed from 6 isoprenoid units
4. Formation of lanosterol
5. Formation of cholesterol
1674
How is the cholesterol ring eliminated?
Through conversion to bile salts then secretion to bile
1675
Bile acid synthesis, found in the liver and Cytosol, rate limiting enzyme is?
Cholesterol-7-a-hydroxylase
1676
What are the primary bile acids?
Cholic acid
| Chenocholic acid
1677
What are the two amino acids used in bile acid conjugation to form bile salts?
Taurine and glycine
1678
What are the secondary bile acids?
Deoxycholic acid
| Lithocholic acid
1679
Where does steroid hormone synthesis occur?
SER of the adrenal glands, ovaries and testes, and placenta
1680
What is blocked by the drug aminogluthetimide?
The conversion of cholesterol to pregnenolone by desmolase
1681
The enzyme responsible for the breakdown of TAG to FA and:
A) 2-MAG from diet
B) FREE glycerol from chylomicrons and VLDL
C) 2-MAG from adipose
A) pancreatic lipase
B) Lipoprotein lipase
C) hormone sensitive lipase
1682
Lipoprotein with the largest percentage of TG
Chylomicrons
1683
Lipoprotein with the largest percentage of cholesteryl esters
LDL
1684
Chylomicrons transport TG and cholesterol from where to where?
Intestines to tissues
1685
VLDL transports TG from where to where?
Liver to tissues
1686
What apoprotein activates lipoprotein lipase?
APO-CII
1687
What apolipoprotein uptakes remnants by the liver?
APO E
1688
Apolipoprotein B-48 is used by chylomicrons which are created by the?
Epithelial cells
1689
What apolipoprotein is secreted by the liver for VDL?
B-100
1690
How does IDL become LDL?
By picking up cholesterol from HD!
1691
Which apoprotein delivers cholesterol into cells?
LDL
1692
Which apolipoprotein is used by HDL to activate lecithin cholesterol acyl transferase or LCAT to produce cholesterol esters?
APO-A1
1693
Difference between Type II familial hypercholesterolemia and type IV familial hypertriglyceredemia?
The former has high LDL leader to xanthomas and xanthelasmas with increased risk of atherosclerosis and CHD
The latter has increased VLDL production leading to a triad of
1. DM type 2
2. CAD
3. Obesity
1694
Phospholipid is composed of
DAG
Alcohol
Phosphodiester bond
1695
Most abundant phospholipid which is important in nervous transmission
Phosphatidylcholine
1696
Phospholipid playing a role in apoptosis
Phosphatidyl serine
1697
Phospholipid that is a major component of surfactant?
Dipalmitoylphosphatidylcholine
1698
Phospholipid reservoir for arachidonic acid in the membranes
Phosphatidylinositol
1699
What phospholipid is essential in mitochondrial function which is also used as a non-troponemal test due to its ability to act as an antigen?
Cardiolipin
1700
```
Composition of these glycolipids:
Ceramide
Cerebroside
Globoside
Ganglioside
Sulfatide
```
Ceramide: sphingosine + FA
```
Ceramide + ________
Glucose or galactose = Cerebroside
Oligosacchardide = Globoside
N-acetylneuramic acid = Ganglioside
Sulfated galactose = Sulfatide
```
1701
Hexosaminidase a ficiency leading to Ssx like cherry red macula, MR, hypotonia
Tay-Sachs disease
1702
A-galactosidase deficiency leading to 3Rs: recessive x-linked, rash, renal failure
Fabrys disease
1703
B-glucosidase deficiency leading to hepatosplenomegaly and erosion of long bones
Gauchers dissease
1704
Sphingomyelinase deficiency leading to hepatosplenomegaly
Nieman-pick disease
1705
The set of all proteins expressed by an individual at a particular time
Proteome
1706
Aims to identify the entire complement of proteins elaborated by a cell under diverse conditions
Proteomics
1707
What amino acid is needed to form ALA in heme synthesis?
Glycine combined with succinyl CoA
1708
Which amino acid carries nitrogen from the liver?
Alanine
1709
Which amino acids are implicated in maple syrup disease
valine, lucine, isoleucine
1710
What enzyme is responsible for the buildup of phenyl lactate, phenyl acetate, and phenylpyruvate?
Phenylalanine hydroxylase
1711
What amino acid is the precursor for niacin, serotonin, and melatonin?
Serotonin
1712
What is the amino acid precursor for homocysteine?
Methionine
1713
What amino acid contributes to the fibrous structure of collagen and interrupts a-helices in globular proteins?
Proline
1714
Increase of the combination of this Amino acid is responsible for the curly hair of people?
Cysteine + cysteine = cystine
1715
Amino acids with sites for O-linked glycosylation in the Golgi apparatus?
Serine and threonine
1716
Site for n-linked glycosylation in the ER
Asparagine
1717
Amino acid deaminated by an enzyme which results in the formation of ammonia. This is the major carrier of nitrogen to the liver from peripheral tissues,
Glutaminase deaminates glutamine
1718
Amino acid used in the determination for Folic acid deficiency. What is the test called?
Histidine used in the N-forminoglutamate excretion test
| Increased amounts of FIGu in urine by Folic acid deficient individuals after histindine intake
1719
Precursor amino acid for creatinine, urea, nitric oxide
Arginine
1720
Essential amino acids that cannot be synthesized by the body and must come from the diet
PVT TIM HALL always ARGues and never TYRes
Phenylalanine, valine, tryptophan, threonine' isoleucine, methionine, histidine, argenine, Leucine, Lysine
1721
Heme is a complex of?
Protoporphorin IX and heme
1722
What is the Bohr effect?
HBO2 + H+ HbH + O2
1723
What is an oxidized for of HB (Fe 3+) that does not bind O2 readily which could lead to chocolate cyanosis ? It is treated with oral methylene blue or ascorbic acid up to IV methylene blue.
Methemoglobin
1724
Hemoglobin bound to carbon monoxide instead of O2 leading to a cherry pink color.
Carboxyhemoglobin
1725
HB bound to carbon dioxide is called
Carbaminohenoglobin
1726
Classification of alpha and beta thalassemia
Alpha: silent carrier, a-thalassemia trait, Hb H disease, hydrops fetalis
Beta: B-thalassemia minor and major
1727
Most frequently affected collagen in Ehler Danlos syndrome leading to hyper extensible skin, tendency to bleed, hyper mobile joints, and increased risk for berry aneurysms.
Collagen type 3
1728
Collagen I mutation leading to bendable and easily fractured bones. Accompanied with blue sclerae, hearing loss, and dental imperfections.
Osteogenesis imperfecta
1729
Vitamin C deficiency leading to decreased hydroxylation of collagen. This leads to sore spongy gums, loose teeth, poor wound healing, and petecchiae on skin and mucous membranes.
Scurvy
1730
Type IV collagen defect leading to hematuria and ESRD
Alpert syndrome
1731
Collagen defect leading to kinky hair due to a deficiency of copper required by lysyl oxidase to strengthen collagen fibers.
Menke syndrome
1732
Skin breaking and blisters as a result for minor trauma. This disease is due to a defect in collage VII.
Epidermolysis bullosa
1733
Like collagen elastin has pro line and Lysine but has little and no?
Hydroxyproline
| Hydroxylysine
1734
Protein degradation mechanisms of nitrogen
Energy dependent ubiquitin-proteosome mechanism
| Non-energy dependent degradation enzyme
1735
Phases in amino acid catabolism
First phase: removal of a-amino group forming ammonia and a corresponding ketoacid
Second phase: carbon skeletons of a-ketoacids are converted to common intermediates of energy producing metabolic pathwas
1736
Two main steps in nitrogen removal from AA
1. Transamination
| 2. Oxidative deamination
1737
Where does transamination occur?
All cells of the body
1738
All but two amino acids transfer their amino groups to a-ketoglutarate except?
Lysine and threonine
1739
What is the coenzyme for the two aminotransferases?
Pyridoxal phosphate (vitamin B6)
1740
Oxidative deamination occurs where and for which amino acid only?
Liver and kidney
| Only glutamate
1741
Glutamate is oxidized by glutamate dehydrogenases and deaminated to form ?
free ammonia which is used to make urea
1742
What does the conversion of glutamate to a-ketoglutarate yield? What about vice versa?
Glutamate -> a ketoglutarate NH3 + NADH
| A ketoglutarate -> glutamate NADP+ + NH3
1743
How is excess nitrogen removal from peripheral tissues removed?
1. Glutamine: via glutamate + ammonia (through Flutamide synthaetase)
2. Alanine: via glucose -> pyruvate + glutamate -> alanine cycle
1744
Glutaminase deaminates glutamine to produce ammonium ion which is excreted from the body. Where are the two tissues this enzyme could be located?
Kidneys and small intestines
1745
Another name for urea cycle
Ornithine cycle or krebs-henseleit cycle
1746
What are the donors of the urea molecule?
1. NH3 from free ammonia
2. NH3 from aspartate
3. 1C and 1O from CO2
1747
Reactions in the urea cycle
1. Formation of carbamoyl phosphate (via carbamoyl phosphate synthetase I)
2. Formation of citrulline (via Ornithine transcarbamoylase)
3. Synthesis of arginosuccinate (arginosuccinate synthetase)
4. Cleavage of arginosuccinate to form arginine (Arginosuccinase)
5. Arginine cleavage to yield urea and Ornithine (arginase)
1748
Rate limiting step of urea cycle
Carbamoyl phosphate synthetase I
1749
Energy requirement of urea cycle
4 ATP
1750
Co factors of urea cycle
N-acetylglutamate
| Biotin
1751
Hereditary hyperammonemia produces symptoms such as
Hyperammonemia, elevated blood glutamine, decreased BUN
| Parents with lethargy, vomiting, hyperventilation, convulsions, cerebral edema, coma, and death
1752
Treatment for hereditary hyperammonemia
Low protein diet
| Administration of sodium benzoate or phenylpyruvate to capture and excrete excess nitrogen
1753
Ketogenic carbon skeletons of AA
Leucine
Lysine
Yields acetoacetate or acetyl-coa/ acetoacetyl-coa
1754
Ketogenic and glucogenic carbon skeletons of AA
```
WIFY
Phenylalanine
Isoleucine
Tryptophan
Tyrosine
```
Yields Ketogenic and glucose or glycogen by products
1755
This amino acid acts as a raw material in the biosynthesis of Heme, purines, creatine
Glycine
1756
This amino acid acts as a raw material in the biosynthesis of phospholipid, sphingolipid, purines, thymine
Serine
1757
This amino acid acts as a raw material in the biosynthesis of GABA
Glutamate
1758
This amino acid acts as a raw material in the biosynthesis of creatine, polyamines, nitric oxide
Arginine
1759
This amino acid acts as a raw material in the biosynthesis of serotonin, NAD+, NADP+, melatonin
Tryptophan
1760
This amino acid acts as a raw material in the biosynthesis of catecholamines, thyroid hormones, melanin
Tyrosine
1761
3 hormones dependent on tyrosine
Thyroid hormones
Melanin
Catecholamines
1762
Deficiency of homogenistic acid oxidase in the degrative pathway of tyrosine which results in urine turning to black on standing with dark connective tissues (ochronosis)
Alkaptonuria
1763
Congenital deficiency due tyrosinase deficieny or defective tyrosine transporters which leads to an increased risk for skin cancer.
Albinism
1764
Autosomal recessive disorder that may either be due to decreased methionine, increased cysteine, B6, and folate or decreased affinity for cystathione synthase. This results in mental retardation, osteoporosis, tall stature, lens subluxation, and atherosclerosis.
Homocystinuria
1765
Common inherited defect of renal tubular amino acid transporter for its parent compound, Ornithine, Lysine, and arginine, in the PCT of the kidneys. It eventually precipitates and cause staghorn caliculi. What is its treatment?
Cystinuria is treated with acetazolamide to alkalinize the urine
1766
The initial and last three steps of heme synthesis occurs in?
The mitochondria
1767
Heme synthesis summary
1. Formation of ALA (via ALA synthase and B6)
2. Formation of porphobilinogen
3. Formation of uroporphyrinogen
4. Formation of heme
1768
Lead inhibits what two steps in heme synthesis?
1. Introduction of Fe 2+ into protoporphyrin IX via ferrochelatase
2. Condensation of two ALA molecules by zinc containing ALA dehydratase
1769
Where is B6 a cofactors of?
1. Heme synthesis
2. Synthesis of cystathionine from homocysteine
3. Transamination between alanine and a-ketoglutarate
1770
Most common porphyria
Porphyria cutanea tarda
1771
Which part of heme synthesis do these symptoms appear?
1. Photosensitivity
2. Neuropsychiatric symptoms
1. After ring formation
| 2. Before ring formation
1772
Pyridoxine ficiency associated with isoniazid therapy results in this histopathologic finding
Sideroblastic anemia with ringed sideroblast
1773
Poisoning due to this heavy metal leads to coar basophilic stippling of RBC, peripheral neuropathy, lines in gums, increas in urinary ALA and free erythrocytes porphorin
lead poisoning
1774
Microcytic hypo chromic anemia is found in
IDA
Thalassemia
Lead poisoning
1775
Megaloblastic anemia is found in
Folate or B12 deficiency
| Pernicious anemia
1776
Normoyctic normochromic anemia is found in
Anemia of chronic kidney disease
| Blood loss
1777
Increase in MCHC is found in
Hereditary spherocytosis
1778
Summary of heme degradation
1. Formation of bilirubin
2. Uptake of bilirubin by the liver
3. Formation of bilirubin diglucoronide
4. Secretion of bilirubin into bile
5. Formation of urobilins in the intestine
1779
Colors of biliverdin, bilirubin, urobilinogen, stercolin, urobilin
```
Biliverdin: green
Bilirubin: red orange
Urobilinogen: colorless
Stercolin: brown orange red
Urobilin: yellow
```
1780
Examples of unconjugated hyperbilirubinemia
```
Hemolytic anemia
Physiologic jaundice
Crigler-najjar syndrome types I and II
Gilbert syndrome
Toxic hyperbilirubinemia
```
1781
Examples of conjugated hyperbilirubinemia
Biliary tree obstruction
Dubin-Johnson syndrome
Rotor syndrome
1782
What reaction measures total and direct bilirubin?
Van den bergs reaction
1783
What enzyme activates fatty acid for metabolism use?
Fatty-acyl-CoA synthetase
1784
Cofactor required for fatty acid activation
Vitamin B5 or Panthotenic acid
1785
Energy required to activate fatty acid
2 ATP
1786
What is the product formed in fatty acid synthesis?
Palmitate (16:0)
1787
Where does fatty acid synthesis occur?
Cytosol
Major: Liver and lactating mammary glands
Minor: adipose tissue
1788
Substrates for fatty acid synthesis
1 acetyl CoA
7 malonyl CoA
NADPH
ATP
1789
Rate limiting step in fatty acid synthesis
Acetyl CoA + ATP -> malonyl CoA
| Enzyme: acetyl CoA carboxylase
1790
Steps in fatty acid synthesis
1. Synthesis of cytoplasmic acetyl CoA (transfer of mitochondrial acetyl CoA to cytoplasm via citrate shuttle)
2. Acetyl CoA carboxylation to malonyl CoA (via acetyl CoA carboxylase with biotin) [+ insulin, citrate]
3. Assembly of palmitate (via fatty acid synthase and Vit B5)
1791
Steps in palmitate assembly
1. Condensation
2. Reduction
3. Dehydration
4. Reduction
1792
What is the fate of Palmitate after its production?
1. Further elongation in SER and mitochondria
| 2. Desaturated in the ER (but not past the 9th carbon)
1793
Main storage form of fatty acids
Triacylglycerols
1794
Where does TAG synthesis occur?
Liver and adipose tissue
1795
Sources of glycerol-3-phosphate
1. DHAP from glycolysis (liver and adipose)
| 2. Phosphorylation of free glycerol (liver)
1796
What enzyme is responsible for the release of free fatty acids from TAGs?
Hormone sensitive lipases
1797
In the bloodstream fatty acids are always bound to?
Albumin
1798
Hormone sensitive lipases can only release what free fatty acids stored in TAG?
C1 & 3 thus resulting in
TAG -> 2 free FA and 2-mono acyl glycerol
1799
Where does B-oxidation of fatty acids occur
Mitochondria of all cells, but the fatty acid activation raft occurs in the Cytosol
Exception: RBC, kidney medulla, neurons, testes
1800
Rate limiting step in B-oxidation
Fatty acyl CoA + carnitine -> fatty acyl carnitine + CoA
| Enzyme: carnitine acyl transferase I
1801
Cutoff number of carbons that do not need a shuttle
Less than 12 carbons
1802
Steps in the carnitine shuttle
1. Fatty acyl synthase activates the fatty acid
2. Carnitine acyl transferase 1 attaches to fatty acyl to carnitine in the outer mitochondrial membrane
3. Fatty acyl-carnitine is shuttle through the inner membrane
4. Carnitine acyl transferase-2 transfers fatty acyl group back to a CoA in the mitochondrial matrix
1803
Steps in beta oxidation
1. Oxidation
2. Hydratiion
3. Oxidation
4. Thiolysis
1804
Beta oxidation of fatty acids with an odd number of carbon atoms releases?
Propionyl CoA which is converted to methylmalonyl coa (requires B12) then to succinyl CoA
1805
Which is responsible for the conversion of very long chain fatty acids?
Peroxisomes but if unsaturated it requires 3,2 enol-CoA isomerase
1806
Energy yield in ATP of beta oxidation of palmitate
129 ATP
7 NADH= 21
7 FAD= 14
8 acetyl CoA= 96
Activation = -2
1807
Intake of this compound depletes the body's NAD+ supply leading to accumulation Of fat in the liver
Alcohol
1808
Type of carnitine deficiency which leads to impaired FA oxidation and ketogenesis with hypoglycemia?
CPT-1 deficiency
1809
Type of carnitine deficiency which affects skeletal muscle and when severe the liver
CPT-2 deficiency
1810
It is a disorder school results in decreased fatty acid oxidation. Without the ATP to support gluconeogenesis, hypoglycemia becomes profound which may eventually leads to SIDS. It is prevented by frequent feeding with high carbohydrate and low fat diet.
Medium-chain fatty acyl-CoA dehydrogenase (MCAD) deficiency
1811
Associated with eating unripe fruit of the akee tree which contains hypoglycin thus activating MC and SC acyl CoA dehydrogenase
Jamaican vomiting sickness
1812
Rare neurological disorder which results to the accumulation of phytanic acid found in plant food stuff which blocks Boxidation
Refsum disease
1813
Cerebrohepatorenal syndrome resulting from the absence of peroxisomes in all tissues, it is characterized by liver dysfunction, jaundice, MR, weakness, hypotonia, and craniofacial dimorphism
Zellweger syndrome
1814
Defect in peroxismal activation of VLCFA thus leading to its accumulation. Ssx: apathy, behavral change, then visual loss spasticity, ataxia. All due to the fact since VLCFA are found in myelin tissue.
X-lied adrenoleukodystrophy
1815
Where does ketogenesis occur?
Liver mitochondria
1816
Products of ketogenesis
Acetoacetate and B-hydroxybutyrate (fuel)
| Acetone (cannot be used as fuel)
1817
Rate limiting step of ketogenesis
Acetoacetyl CoA + acetyl CoA --(HMG CoA synthase)--> HMG CoA
1818
What are the initial products that lead to the formation of acetyl CoA in ketogenolysis?
B-hydroxybutyrate -> acetoacetate -> acetyl coa
1819
What peripheral tissues can oxidize ketone bodes?
Those with mitochondria like the renal cortex, brain, and skeletal muscle
1820
Why cant liver convert acetoacetate to acetyl CoA?
It lacks succinyl-CoA acetoacetyl-CoA reductase (thiophorase)
1821
What is the Urine test for ketones? What ketone type does not it detect?
Nitroprusside test
Does not detect b-hydroxybutyrate
1822
Which part of cholesterol can a fatty acid attach to form a cholesteryl ester?
Single hydroxyl group of carbon 3 of the alpha ring
1823
Where does cholesterol synthesis occur?
All cells in the Cytosol and SER majority of which are found in the liver and intestines
1824
Substrates of cholesterol synthesis
Acetyl CoA, NADPH, ATP
1825
Rate limiting step in cholesterol synthesis
HMG CoA --(HMG CoA reductase)--> mevalonate
1826
Steps in Cholestid synthesis
1. Biosynthesis of mevalonate
2. Formation of isoprenoid units
3. Isoprene unit is formed from 6 isoprenoid units
4. Formation of lanosterol
5. Formation of cholesterol
1827
How is the cholesterol ring eliminated?
Through conversion to bile salts then secretion to bile
1828
Bile acid synthesis, found in the liver and Cytosol, rate limiting enzyme is?
Cholesterol-7-a-hydroxylase
1829
What are the primary bile acids?
Cholic acid
| Chenocholic acid
1830
What are the two amino acids used in bile acid conjugation to form bile salts?
Taurine and glycine
1831
What are the secondary bile acids?
Deoxycholic acid
| Lithocholic acid
1832
Where does steroid hormone synthesis occur?
SER of the adrenal glands, ovaries and testes, and placenta
1833
What is blocked by the drug aminogluthetimide?
The conversion of cholesterol to pregnenolone by desmolase
1834
The enzyme responsible for the breakdown of TAG to FA and:
A) 2-MAG from diet
B) FREE glycerol from chylomicrons and VLDL
C) 2-MAG from adipose
A) pancreatic lipase
B) Lipoprotein lipase
C) hormone sensitive lipase
1835
Lipoprotein with the largest percentage of TG
Chylomicrons
1836
Lipoprotein with the largest percentage of cholesteryl esters
LDL
1837
Chylomicrons transport TG and cholesterol from where to where?
Intestines to tissues
1838
VLDL transports TG from where to where?
Liver to tissues
1839
What apoprotein activates lipoprotein lipase?
APO-CII
1840
What apolipoprotein uptakes remnants by the liver?
APO E
1841
Apolipoprotein B-48 is used by chylomicrons which are created by the?
Epithelial cells
1842
What apolipoprotein is secreted by the liver for VDL?
B-100
1843
How does IDL become LDL?
By picking up cholesterol from HD!
1844
Which apoprotein delivers cholesterol into cells?
LDL
1845
Which apolipoprotein is used by HDL to activate lecithin cholesterol acyl transferase or LCAT to produce cholesterol esters?
APO-A1
1846
Difference between Type II familial hypercholesterolemia and type IV familial hypertriglyceredemia?
The former has high LDL leader to xanthomas and xanthelasmas with increased risk of atherosclerosis and CHD
The latter has increased VLDL production leading to a triad of
1. DM type 2
2. CAD
3. Obesity
1847
Phospholipid is composed of
DAG
Alcohol
Phosphodiester bond
1848
Most abundant phospholipid which is important in nervous transmission
Phosphatidylcholine
1849
Phospholipid playing a role in apoptosis
Phosphatidyl serine
1850
Phospholipid that is a major component of surfactant?
Dipalmitoylphosphatidylcholine
1851
Phospholipid reservoir for arachidonic acid in the membranes
Phosphatidylinositol
1852
What phospholipid is essential in mitochondrial function which is also used as a non-troponemal test due to its ability to act as an antigen?
Cardiolipin
1853
```
Composition of these glycolipids:
Ceramide
Cerebroside
Globoside
Ganglioside
Sulfatide
```
Ceramide: sphingosine + FA
```
Ceramide + ________
Glucose or galactose = Cerebroside
Oligosacchardide = Globoside
N-acetylneuramic acid = Ganglioside
Sulfated galactose = Sulfatide
```
1854
Hexosaminidase a ficiency leading to Ssx like cherry red macula, MR, hypotonia
Tay-Sachs disease
1855
A-galactosidase deficiency leading to 3Rs: recessive x-linked, rash, renal failure
Fabrys disease
1856
B-glucosidase deficiency leading to hepatosplenomegaly and erosion of long bones
Gauchers dissease
1857
Sphingomyelinase deficiency leading to hepatosplenomegaly
Nieman-pick disease
1858
The set of all proteins expressed by an individual at a particular time
Proteome
1859
Aims to identify the entire complement of proteins elaborated by a cell under diverse conditions
Proteomics
1860
What amino acid is needed to form ALA in heme synthesis?
Glycine combined with succinyl CoA
1861
Which amino acid carries nitrogen from the liver?
Alanine
1862
Which amino acids are implicated in maple syrup disease
valine, lucine, isoleucine
1863
What enzyme is responsible for the buildup of phenyl lactate, phenyl acetate, and phenylpyruvate?
Phenylalanine hydroxylase
1864
What amino acid is the precursor for niacin, serotonin, and melatonin?
Serotonin
1865
What is the amino acid precursor for homocysteine?
Methionine
1866
What amino acid contributes to the fibrous structure of collagen and interrupts a-helices in globular proteins?
Proline
1867
Increase of the combination of this Amino acid is responsible for the curly hair of people?
Cysteine + cysteine = cystine
1868
Amino acids with sites for O-linked glycosylation in the Golgi apparatus?
Serine and threonine
1869
Site for n-linked glycosylation in the ER
Asparagine
1870
Amino acid deaminated by an enzyme which results in the formation of ammonia. This is the major carrier of nitrogen to the liver from peripheral tissues,
Glutaminase deaminates glutamine
1871
Amino acid used in the determination for Folic acid deficiency. What is the test called?
Histidine used in the N-forminoglutamate excretion test
| Increased amounts of FIGu in urine by Folic acid deficient individuals after histindine intake
1872
Precursor amino acid for creatinine, urea, nitric oxide
Arginine
1873
Essential amino acids that cannot be synthesized by the body and must come from the diet
PVT TIM HALL always ARGues and never TYRes
Phenylalanine, valine, tryptophan, threonine' isoleucine, methionine, histidine, argenine, Leucine, Lysine
1874
Heme is a complex of?
Protoporphorin IX and heme
1875
What is the Bohr effect?
HBO2 + H+ HbH + O2
1876
What is an oxidized for of HB (Fe 3+) that does not bind O2 readily which could lead to chocolate cyanosis ? It is treated with oral methylene blue or ascorbic acid up to IV methylene blue.
Methemoglobin
1877
Hemoglobin bound to carbon monoxide instead of O2 leading to a cherry pink color.
Carboxyhemoglobin
1878
HB bound to carbon dioxide is called
Carbaminohenoglobin
1879
Classification of alpha and beta thalassemia
Alpha: silent carrier, a-thalassemia trait, Hb H disease, hydrops fetalis
Beta: B-thalassemia minor and major
1880
Most frequently affected collagen in Ehler Danlos syndrome leading to hyper extensible skin, tendency to bleed, hyper mobile joints, and increased risk for berry aneurysms.
Collagen type 3
1881
Collagen I mutation leading to bendable and easily fractured bones. Accompanied with blue sclerae, hearing loss, and dental imperfections.
Osteogenesis imperfecta
1882
Vitamin C deficiency leading to decreased hydroxylation of collagen. This leads to sore spongy gums, loose teeth, poor wound healing, and petecchiae on skin and mucous membranes.
Scurvy
1883
Type IV collagen defect leading to hematuria and ESRD
Alpert syndrome
1884
Collagen defect leading to kinky hair due to a deficiency of copper required by lysyl oxidase to strengthen collagen fibers.
Menke syndrome
1885
Skin breaking and blisters as a result for minor trauma. This disease is due to a defect in collage VII.
Epidermolysis bullosa
1886
Like collagen elastin has pro line and Lysine but has little and no?
Hydroxyproline
| Hydroxylysine
1887
Protein degradation mechanisms of nitrogen
Energy dependent ubiquitin-proteosome mechanism
| Non-energy dependent degradation enzyme
1888
Phases in amino acid catabolism
First phase: removal of a-amino group forming ammonia and a corresponding ketoacid
Second phase: carbon skeletons of a-ketoacids are converted to common intermediates of energy producing metabolic pathwas
1889
Two main steps in nitrogen removal from AA
1. Transamination
| 2. Oxidative deamination
1890
Where does transamination occur?
All cells of the body
1891
All but two amino acids transfer their amino groups to a-ketoglutarate except?
Lysine and threonine
1892
What is the coenzyme for the two aminotransferases?
Pyridoxal phosphate (vitamin B6)
1893
Oxidative deamination occurs where and for which amino acid only?
Liver and kidney
| Only glutamate
1894
Glutamate is oxidized by glutamate dehydrogenases and deaminated to form ?
free ammonia which is used to make urea
1895
What does the conversion of glutamate to a-ketoglutarate yield? What about vice versa?
Glutamate -> a ketoglutarate NH3 + NADH
| A ketoglutarate -> glutamate NADP+ + NH3
1896
How is excess nitrogen removal from peripheral tissues removed?
1. Glutamine: via glutamate + ammonia (through Flutamide synthaetase)
2. Alanine: via glucose -> pyruvate + glutamate -> alanine cycle
1897
Glutaminase deaminates glutamine to produce ammonium ion which is excreted from the body. Where are the two tissues this enzyme could be located?
Kidneys and small intestines
1898
Another name for urea cycle
Ornithine cycle or krebs-henseleit cycle
1899
What are the donors of the urea molecule?
1. NH3 from free ammonia
2. NH3 from aspartate
3. 1C and 1O from CO2
1900
Reactions in the urea cycle
1. Formation of carbamoyl phosphate (via carbamoyl phosphate synthetase I)
2. Formation of citrulline (via Ornithine transcarbamoylase)
3. Synthesis of arginosuccinate (arginosuccinate synthetase)
4. Cleavage of arginosuccinate to form arginine (Arginosuccinase)
5. Arginine cleavage to yield urea and Ornithine (arginase)
1901
Rate limiting step of urea cycle
Carbamoyl phosphate synthetase I
1902
Energy requirement of urea cycle
4 ATP
1903
Co factors of urea cycle
N-acetylglutamate
| Biotin
1904
Hereditary hyperammonemia produces symptoms such as
Hyperammonemia, elevated blood glutamine, decreased BUN
| Parents with lethargy, vomiting, hyperventilation, convulsions, cerebral edema, coma, and death
1905
Treatment for hereditary hyperammonemia
Low protein diet
| Administration of sodium benzoate or phenylpyruvate to capture and excrete excess nitrogen
1906
Ketogenic carbon skeletons of AA
Leucine
Lysine
Yields acetoacetate or acetyl-coa/ acetoacetyl-coa
1907
Ketogenic and glucogenic carbon skeletons of AA
```
WIFY
Phenylalanine
Isoleucine
Tryptophan
Tyrosine
```
Yields Ketogenic and glucose or glycogen by products
1908
This amino acid acts as a raw material in the biosynthesis of Heme, purines, creatine
Glycine
1909
This amino acid acts as a raw material in the biosynthesis of phospholipid, sphingolipid, purines, thymine
Serine
1910
This amino acid acts as a raw material in the biosynthesis of GABA
Glutamate
1911
This amino acid acts as a raw material in the biosynthesis of creatine, polyamines, nitric oxide
Arginine
1912
This amino acid acts as a raw material in the biosynthesis of serotonin, NAD+, NADP+, melatonin
Tryptophan
1913
This amino acid acts as a raw material in the biosynthesis of catecholamines, thyroid hormones, melanin
Tyrosine
1914
3 hormones dependent on tyrosine
Thyroid hormones
Melanin
Catecholamines
1915
Deficiency of homogenistic acid oxidase in the degrative pathway of tyrosine which results in urine turning to black on standing with dark connective tissues (ochronosis)
Alkaptonuria
1916
Congenital deficiency due tyrosinase deficieny or defective tyrosine transporters which leads to an increased risk for skin cancer.
Albinism
1917
Autosomal recessive disorder that may either be due to decreased methionine, increased cysteine, B6, and folate or decreased affinity for cystathione synthase. This results in mental retardation, osteoporosis, tall stature, lens subluxation, and atherosclerosis.
Homocystinuria
1918
Common inherited defect of renal tubular amino acid transporter for its parent compound, Ornithine, Lysine, and arginine, in the PCT of the kidneys. It eventually precipitates and cause staghorn caliculi. What is its treatment?
Cystinuria is treated with acetazolamide to alkalinize the urine
1919
The initial and last three steps of heme synthesis occurs in?
The mitochondria
1920
Heme synthesis summary
1. Formation of ALA (via ALA synthase and B6)
2. Formation of porphobilinogen
3. Formation of uroporphyrinogen
4. Formation of heme
1921
Lead inhibits what two steps in heme synthesis?
1. Introduction of Fe 2+ into protoporphyrin IX via ferrochelatase
2. Condensation of two ALA molecules by zinc containing ALA dehydratase
1922
Where is B6 a cofactors of?
1. Heme synthesis
2. Synthesis of cystathionine from homocysteine
3. Transamination between alanine and a-ketoglutarate
1923
Most common porphyria
Porphyria cutanea tarda
1924
Which part of heme synthesis do these symptoms appear?
1. Photosensitivity
2. Neuropsychiatric symptoms
1. After ring formation
| 2. Before ring formation
1925
Pyridoxine ficiency associated with isoniazid therapy results in this histopathologic finding
Sideroblastic anemia with ringed sideroblast
1926
Poisoning due to this heavy metal leads to coar basophilic stippling of RBC, peripheral neuropathy, lines in gums, increas in urinary ALA and free erythrocytes porphorin
lead poisoning
1927
Microcytic hypo chromic anemia is found in
IDA
Thalassemia
Lead poisoning
1928
Megaloblastic anemia is found in
Folate or B12 deficiency
| Pernicious anemia
1929
Normoyctic normochromic anemia is found in
Anemia of chronic kidney disease
| Blood loss
1930
Increase in MCHC is found in
Hereditary spherocytosis
1931
Summary of heme degradation
1. Formation of bilirubin
2. Uptake of bilirubin by the liver
3. Formation of bilirubin diglucoronide
4. Secretion of bilirubin into bile
5. Formation of urobilins in the intestine
1932
Colors of biliverdin, bilirubin, urobilinogen, stercolin, urobilin
```
Biliverdin: green
Bilirubin: red orange
Urobilinogen: colorless
Stercolin: brown orange red
Urobilin: yellow
```
1933
Examples of unconjugated hyperbilirubinemia
```
Hemolytic anemia
Physiologic jaundice
Crigler-najjar syndrome types I and II
Gilbert syndrome
Toxic hyperbilirubinemia
```
1934
Examples of conjugated hyperbilirubinemia
Biliary tree obstruction
Dubin-Johnson syndrome
Rotor syndrome
1935
What reaction measures total and direct bilirubin?
Van den bergs reaction
1936
What enzyme activates fatty acid for metabolism use?
Fatty-acyl-CoA synthetase
1937
Cofactor required for fatty acid activation
Vitamin B5 or Panthotenic acid
1938
Energy required to activate fatty acid
2 ATP
1939
What is the product formed in fatty acid synthesis?
Palmitate (16:0)
1940
Where does fatty acid synthesis occur?
Cytosol
Major: Liver and lactating mammary glands
Minor: adipose tissue
1941
Substrates for fatty acid synthesis
1 acetyl CoA
7 malonyl CoA
NADPH
ATP
1942
Rate limiting step in fatty acid synthesis
Acetyl CoA + ATP -> malonyl CoA
| Enzyme: acetyl CoA carboxylase
1943
Steps in fatty acid synthesis
1. Synthesis of cytoplasmic acetyl CoA (transfer of mitochondrial acetyl CoA to cytoplasm via citrate shuttle)
2. Acetyl CoA carboxylation to malonyl CoA (via acetyl CoA carboxylase with biotin) [+ insulin, citrate]
3. Assembly of palmitate (via fatty acid synthase and Vit B5)
1944
Steps in palmitate assembly
1. Condensation
2. Reduction
3. Dehydration
4. Reduction
1945
What is the fate of Palmitate after its production?
1. Further elongation in SER and mitochondria
| 2. Desaturated in the ER (but not past the 9th carbon)
1946
Main storage form of fatty acids
Triacylglycerols
1947
Where does TAG synthesis occur?
Liver and adipose tissue
1948
Sources of glycerol-3-phosphate
1. DHAP from glycolysis (liver and adipose)
| 2. Phosphorylation of free glycerol (liver)
1949
What enzyme is responsible for the release of free fatty acids from TAGs?
Hormone sensitive lipases
1950
In the bloodstream fatty acids are always bound to?
Albumin
1951
Hormone sensitive lipases can only release what free fatty acids stored in TAG?
C1 & 3 thus resulting in
TAG -> 2 free FA and 2-mono acyl glycerol
1952
Where does B-oxidation of fatty acids occur
Mitochondria of all cells, but the fatty acid activation raft occurs in the Cytosol
Exception: RBC, kidney medulla, neurons, testes
1953
Rate limiting step in B-oxidation
Fatty acyl CoA + carnitine -> fatty acyl carnitine + CoA
| Enzyme: carnitine acyl transferase I
1954
Cutoff number of carbons that do not need a shuttle
Less than 12 carbons
1955
Steps in the carnitine shuttle
1. Fatty acyl synthase activates the fatty acid
2. Carnitine acyl transferase 1 attaches to fatty acyl to carnitine in the outer mitochondrial membrane
3. Fatty acyl-carnitine is shuttle through the inner membrane
4. Carnitine acyl transferase-2 transfers fatty acyl group back to a CoA in the mitochondrial matrix
1956
Steps in beta oxidation
1. Oxidation
2. Hydratiion
3. Oxidation
4. Thiolysis
1957
Beta oxidation of fatty acids with an odd number of carbon atoms releases?
Propionyl CoA which is converted to methylmalonyl coa (requires B12) then to succinyl CoA
1958
Which is responsible for the conversion of very long chain fatty acids?
Peroxisomes but if unsaturated it requires 3,2 enol-CoA isomerase
1959
Energy yield in ATP of beta oxidation of palmitate
129 ATP
7 NADH= 21
7 FAD= 14
8 acetyl CoA= 96
Activation = -2
1960
Intake of this compound depletes the body's NAD+ supply leading to accumulation Of fat in the liver
Alcohol
1961
Type of carnitine deficiency which leads to impaired FA oxidation and ketogenesis with hypoglycemia?
CPT-1 deficiency
1962
Type of carnitine deficiency which affects skeletal muscle and when severe the liver
CPT-2 deficiency
1963
It is a disorder school results in decreased fatty acid oxidation. Without the ATP to support gluconeogenesis, hypoglycemia becomes profound which may eventually leads to SIDS. It is prevented by frequent feeding with high carbohydrate and low fat diet.
Medium-chain fatty acyl-CoA dehydrogenase (MCAD) deficiency
1964
Associated with eating unripe fruit of the akee tree which contains hypoglycin thus activating MC and SC acyl CoA dehydrogenase
Jamaican vomiting sickness
1965
Rare neurological disorder which results to the accumulation of phytanic acid found in plant food stuff which blocks Boxidation
Refsum disease
1966
Cerebrohepatorenal syndrome resulting from the absence of peroxisomes in all tissues, it is characterized by liver dysfunction, jaundice, MR, weakness, hypotonia, and craniofacial dimorphism
Zellweger syndrome
1967
Defect in peroxismal activation of VLCFA thus leading to its accumulation. Ssx: apathy, behavral change, then visual loss spasticity, ataxia. All due to the fact since VLCFA are found in myelin tissue.
X-lied adrenoleukodystrophy
1968
Where does ketogenesis occur?
Liver mitochondria
1969
Products of ketogenesis
Acetoacetate and B-hydroxybutyrate (fuel)
| Acetone (cannot be used as fuel)
1970
Rate limiting step of ketogenesis
Acetoacetyl CoA + acetyl CoA --(HMG CoA synthase)--> HMG CoA
1971
What are the initial products that lead to the formation of acetyl CoA in ketogenolysis?
B-hydroxybutyrate -> acetoacetate -> acetyl coa
1972
What peripheral tissues can oxidize ketone bodes?
Those with mitochondria like the renal cortex, brain, and skeletal muscle
1973
Why cant liver convert acetoacetate to acetyl CoA?
It lacks succinyl-CoA acetoacetyl-CoA reductase (thiophorase)
1974
What is the Urine test for ketones? What ketone type does not it detect?
Nitroprusside test
Does not detect b-hydroxybutyrate
1975
Which part of cholesterol can a fatty acid attach to form a cholesteryl ester?
Single hydroxyl group of carbon 3 of the alpha ring
1976
Where does cholesterol synthesis occur?
All cells in the Cytosol and SER majority of which are found in the liver and intestines
1977
Substrates of cholesterol synthesis
Acetyl CoA, NADPH, ATP
1978
Rate limiting step in cholesterol synthesis
HMG CoA --(HMG CoA reductase)--> mevalonate
1979
Steps in Cholestid synthesis
1. Biosynthesis of mevalonate
2. Formation of isoprenoid units
3. Isoprene unit is formed from 6 isoprenoid units
4. Formation of lanosterol
5. Formation of cholesterol
1980
How is the cholesterol ring eliminated?
Through conversion to bile salts then secretion to bile
1981
Bile acid synthesis, found in the liver and Cytosol, rate limiting enzyme is?
Cholesterol-7-a-hydroxylase
1982
What are the primary bile acids?
Cholic acid
| Chenocholic acid
1983
What are the two amino acids used in bile acid conjugation to form bile salts?
Taurine and glycine
1984
What are the secondary bile acids?
Deoxycholic acid
| Lithocholic acid
1985
Where does steroid hormone synthesis occur?
SER of the adrenal glands, ovaries and testes, and placenta
1986
What is blocked by the drug aminogluthetimide?
The conversion of cholesterol to pregnenolone by desmolase
1987
The enzyme responsible for the breakdown of TAG to FA and:
A) 2-MAG from diet
B) FREE glycerol from chylomicrons and VLDL
C) 2-MAG from adipose
A) pancreatic lipase
B) Lipoprotein lipase
C) hormone sensitive lipase
1988
Lipoprotein with the largest percentage of TG
Chylomicrons
1989
Lipoprotein with the largest percentage of cholesteryl esters
LDL
1990
Chylomicrons transport TG and cholesterol from where to where?
Intestines to tissues
1991
VLDL transports TG from where to where?
Liver to tissues
1992
What apoprotein activates lipoprotein lipase?
APO-CII
1993
What apolipoprotein uptakes remnants by the liver?
APO E
1994
Apolipoprotein B-48 is used by chylomicrons which are created by the?
Epithelial cells
1995
What apolipoprotein is secreted by the liver for VDL?
B-100
1996
How does IDL become LDL?
By picking up cholesterol from HD!
1997
Which apoprotein delivers cholesterol into cells?
LDL
1998
Which apolipoprotein is used by HDL to activate lecithin cholesterol acyl transferase or LCAT to produce cholesterol esters?
APO-A1
1999
Difference between Type II familial hypercholesterolemia and type IV familial hypertriglyceredemia?
The former has high LDL leader to xanthomas and xanthelasmas with increased risk of atherosclerosis and CHD
The latter has increased VLDL production leading to a triad of
1. DM type 2
2. CAD
3. Obesity
2000
Phospholipid is composed of
DAG
Alcohol
Phosphodiester bond
2001
Most abundant phospholipid which is important in nervous transmission
Phosphatidylcholine
2002
Phospholipid playing a role in apoptosis
Phosphatidyl serine
2003
Phospholipid that is a major component of surfactant?
Dipalmitoylphosphatidylcholine
2004
Phospholipid reservoir for arachidonic acid in the membranes
Phosphatidylinositol
2005
What phospholipid is essential in mitochondrial function which is also used as a non-troponemal test due to its ability to act as an antigen?
Cardiolipin
2006
```
Composition of these glycolipids:
Ceramide
Cerebroside
Globoside
Ganglioside
Sulfatide
```
Ceramide: sphingosine + FA
```
Ceramide + ________
Glucose or galactose = Cerebroside
Oligosacchardide = Globoside
N-acetylneuramic acid = Ganglioside
Sulfated galactose = Sulfatide
```
2007
Hexosaminidase a ficiency leading to Ssx like cherry red macula, MR, hypotonia
Tay-Sachs disease
2008
A-galactosidase deficiency leading to 3Rs: recessive x-linked, rash, renal failure
Fabrys disease
2009
B-glucosidase deficiency leading to hepatosplenomegaly and erosion of long bones
Gauchers dissease
2010
Sphingomyelinase deficiency leading to hepatosplenomegaly
Nieman-pick disease
2011
The set of all proteins expressed by an individual at a particular time
Proteome
2012
Aims to identify the entire complement of proteins elaborated by a cell under diverse conditions
Proteomics
2013
What amino acid is needed to form ALA in heme synthesis?
Glycine combined with succinyl CoA
2014
Which amino acid carries nitrogen from the liver?
Alanine
2015
Which amino acids are implicated in maple syrup disease
valine, lucine, isoleucine
2016
What enzyme is responsible for the buildup of phenyl lactate, phenyl acetate, and phenylpyruvate?
Phenylalanine hydroxylase
2017
What amino acid is the precursor for niacin, serotonin, and melatonin?
Serotonin
2018
What is the amino acid precursor for homocysteine?
Methionine
2019
What amino acid contributes to the fibrous structure of collagen and interrupts a-helices in globular proteins?
Proline
2020
Increase of the combination of this Amino acid is responsible for the curly hair of people?
Cysteine + cysteine = cystine
2021
Amino acids with sites for O-linked glycosylation in the Golgi apparatus?
Serine and threonine
2022
Site for n-linked glycosylation in the ER
Asparagine
2023
Amino acid deaminated by an enzyme which results in the formation of ammonia. This is the major carrier of nitrogen to the liver from peripheral tissues,
Glutaminase deaminates glutamine
2024
Amino acid used in the determination for Folic acid deficiency. What is the test called?
Histidine used in the N-forminoglutamate excretion test
| Increased amounts of FIGu in urine by Folic acid deficient individuals after histindine intake
2025
Precursor amino acid for creatinine, urea, nitric oxide
Arginine
2026
Essential amino acids that cannot be synthesized by the body and must come from the diet
PVT TIM HALL always ARGues and never TYRes
Phenylalanine, valine, tryptophan, threonine' isoleucine, methionine, histidine, argenine, Leucine, Lysine
2027
Heme is a complex of?
Protoporphorin IX and heme
2028
What is the Bohr effect?
HBO2 + H+ HbH + O2
2029
What is an oxidized for of HB (Fe 3+) that does not bind O2 readily which could lead to chocolate cyanosis ? It is treated with oral methylene blue or ascorbic acid up to IV methylene blue.
Methemoglobin
2030
Hemoglobin bound to carbon monoxide instead of O2 leading to a cherry pink color.
Carboxyhemoglobin
2031
HB bound to carbon dioxide is called
Carbaminohenoglobin
2032
Classification of alpha and beta thalassemia
Alpha: silent carrier, a-thalassemia trait, Hb H disease, hydrops fetalis
Beta: B-thalassemia minor and major
2033
Most frequently affected collagen in Ehler Danlos syndrome leading to hyper extensible skin, tendency to bleed, hyper mobile joints, and increased risk for berry aneurysms.
Collagen type 3
2034
Collagen I mutation leading to bendable and easily fractured bones. Accompanied with blue sclerae, hearing loss, and dental imperfections.
Osteogenesis imperfecta
2035
Vitamin C deficiency leading to decreased hydroxylation of collagen. This leads to sore spongy gums, loose teeth, poor wound healing, and petecchiae on skin and mucous membranes.
Scurvy
2036
Type IV collagen defect leading to hematuria and ESRD
Alpert syndrome
2037
Collagen defect leading to kinky hair due to a deficiency of copper required by lysyl oxidase to strengthen collagen fibers.
Menke syndrome
2038
Skin breaking and blisters as a result for minor trauma. This disease is due to a defect in collage VII.
Epidermolysis bullosa
2039
Like collagen elastin has pro line and Lysine but has little and no?
Hydroxyproline
| Hydroxylysine
2040
Protein degradation mechanisms of nitrogen
Energy dependent ubiquitin-proteosome mechanism
| Non-energy dependent degradation enzyme
2041
Phases in amino acid catabolism
First phase: removal of a-amino group forming ammonia and a corresponding ketoacid
Second phase: carbon skeletons of a-ketoacids are converted to common intermediates of energy producing metabolic pathwas
2042
Two main steps in nitrogen removal from AA
1. Transamination
| 2. Oxidative deamination
2043
Where does transamination occur?
All cells of the body
2044
All but two amino acids transfer their amino groups to a-ketoglutarate except?
Lysine and threonine
2045
What is the coenzyme for the two aminotransferases?
Pyridoxal phosphate (vitamin B6)
2046
Oxidative deamination occurs where and for which amino acid only?
Liver and kidney
| Only glutamate
2047
Glutamate is oxidized by glutamate dehydrogenases and deaminated to form ?
free ammonia which is used to make urea
2048
What does the conversion of glutamate to a-ketoglutarate yield? What about vice versa?
Glutamate -> a ketoglutarate NH3 + NADH
| A ketoglutarate -> glutamate NADP+ + NH3
2049
How is excess nitrogen removal from peripheral tissues removed?
1. Glutamine: via glutamate + ammonia (through Flutamide synthaetase)
2. Alanine: via glucose -> pyruvate + glutamate -> alanine cycle
2050
Glutaminase deaminates glutamine to produce ammonium ion which is excreted from the body. Where are the two tissues this enzyme could be located?
Kidneys and small intestines
2051
Another name for urea cycle
Ornithine cycle or krebs-henseleit cycle
2052
What are the donors of the urea molecule?
1. NH3 from free ammonia
2. NH3 from aspartate
3. 1C and 1O from CO2
2053
Reactions in the urea cycle
1. Formation of carbamoyl phosphate (via carbamoyl phosphate synthetase I)
2. Formation of citrulline (via Ornithine transcarbamoylase)
3. Synthesis of arginosuccinate (arginosuccinate synthetase)
4. Cleavage of arginosuccinate to form arginine (Arginosuccinase)
5. Arginine cleavage to yield urea and Ornithine (arginase)
2054
Rate limiting step of urea cycle
Carbamoyl phosphate synthetase I
2055
Energy requirement of urea cycle
4 ATP
2056
Co factors of urea cycle
N-acetylglutamate
| Biotin
2057
Hereditary hyperammonemia produces symptoms such as
Hyperammonemia, elevated blood glutamine, decreased BUN
| Parents with lethargy, vomiting, hyperventilation, convulsions, cerebral edema, coma, and death
2058
Treatment for hereditary hyperammonemia
Low protein diet
| Administration of sodium benzoate or phenylpyruvate to capture and excrete excess nitrogen
2059
Ketogenic carbon skeletons of AA
Leucine
Lysine
Yields acetoacetate or acetyl-coa/ acetoacetyl-coa
2060
Ketogenic and glucogenic carbon skeletons of AA
```
WIFY
Phenylalanine
Isoleucine
Tryptophan
Tyrosine
```
Yields Ketogenic and glucose or glycogen by products
2061
This amino acid acts as a raw material in the biosynthesis of Heme, purines, creatine
Glycine
2062
This amino acid acts as a raw material in the biosynthesis of phospholipid, sphingolipid, purines, thymine
Serine
2063
This amino acid acts as a raw material in the biosynthesis of GABA
Glutamate
2064
This amino acid acts as a raw material in the biosynthesis of creatine, polyamines, nitric oxide
Arginine
2065
This amino acid acts as a raw material in the biosynthesis of serotonin, NAD+, NADP+, melatonin
Tryptophan
2066
This amino acid acts as a raw material in the biosynthesis of catecholamines, thyroid hormones, melanin
Tyrosine
2067
3 hormones dependent on tyrosine
Thyroid hormones
Melanin
Catecholamines
2068
Deficiency of homogenistic acid oxidase in the degrative pathway of tyrosine which results in urine turning to black on standing with dark connective tissues (ochronosis)
Alkaptonuria
2069
Congenital deficiency due tyrosinase deficieny or defective tyrosine transporters which leads to an increased risk for skin cancer.
Albinism
2070
Autosomal recessive disorder that may either be due to decreased methionine, increased cysteine, B6, and folate or decreased affinity for cystathione synthase. This results in mental retardation, osteoporosis, tall stature, lens subluxation, and atherosclerosis.
Homocystinuria
2071
Common inherited defect of renal tubular amino acid transporter for its parent compound, Ornithine, Lysine, and arginine, in the PCT of the kidneys. It eventually precipitates and cause staghorn caliculi. What is its treatment?
Cystinuria is treated with acetazolamide to alkalinize the urine
2072
The initial and last three steps of heme synthesis occurs in?
The mitochondria
2073
Heme synthesis summary
1. Formation of ALA (via ALA synthase and B6)
2. Formation of porphobilinogen
3. Formation of uroporphyrinogen
4. Formation of heme
2074
Lead inhibits what two steps in heme synthesis?
1. Introduction of Fe 2+ into protoporphyrin IX via ferrochelatase
2. Condensation of two ALA molecules by zinc containing ALA dehydratase
2075
Where is B6 a cofactors of?
1. Heme synthesis
2. Synthesis of cystathionine from homocysteine
3. Transamination between alanine and a-ketoglutarate
2076
Most common porphyria
Porphyria cutanea tarda
2077
Which part of heme synthesis do these symptoms appear?
1. Photosensitivity
2. Neuropsychiatric symptoms
1. After ring formation
| 2. Before ring formation
2078
Pyridoxine ficiency associated with isoniazid therapy results in this histopathologic finding
Sideroblastic anemia with ringed sideroblast
2079
Poisoning due to this heavy metal leads to coar basophilic stippling of RBC, peripheral neuropathy, lines in gums, increas in urinary ALA and free erythrocytes porphorin
lead poisoning
2080
Microcytic hypo chromic anemia is found in
IDA
Thalassemia
Lead poisoning
2081
Megaloblastic anemia is found in
Folate or B12 deficiency
| Pernicious anemia
2082
Normoyctic normochromic anemia is found in
Anemia of chronic kidney disease
| Blood loss
2083
Increase in MCHC is found in
Hereditary spherocytosis
2084
Summary of heme degradation
1. Formation of bilirubin
2. Uptake of bilirubin by the liver
3. Formation of bilirubin diglucoronide
4. Secretion of bilirubin into bile
5. Formation of urobilins in the intestine
2085
Colors of biliverdin, bilirubin, urobilinogen, stercolin, urobilin
```
Biliverdin: green
Bilirubin: red orange
Urobilinogen: colorless
Stercolin: brown orange red
Urobilin: yellow
```
2086
Examples of unconjugated hyperbilirubinemia
```
Hemolytic anemia
Physiologic jaundice
Crigler-najjar syndrome types I and II
Gilbert syndrome
Toxic hyperbilirubinemia
```
2087
Examples of conjugated hyperbilirubinemia
Biliary tree obstruction
Dubin-Johnson syndrome
Rotor syndrome
2088
What reaction measures total and direct bilirubin?
Van den bergs reaction
2089
What enzyme activates fatty acid for metabolism use?
Fatty-acyl-CoA synthetase
2090
Cofactor required for fatty acid activation
Vitamin B5 or Panthotenic acid
2091
Energy required to activate fatty acid
2 ATP
2092
What is the product formed in fatty acid synthesis?
Palmitate (16:0)
2093
Where does fatty acid synthesis occur?
Cytosol
Major: Liver and lactating mammary glands
Minor: adipose tissue
2094
Substrates for fatty acid synthesis
1 acetyl CoA
7 malonyl CoA
NADPH
ATP
2095
Rate limiting step in fatty acid synthesis
Acetyl CoA + ATP -> malonyl CoA
| Enzyme: acetyl CoA carboxylase
2096
Steps in fatty acid synthesis
1. Synthesis of cytoplasmic acetyl CoA (transfer of mitochondrial acetyl CoA to cytoplasm via citrate shuttle)
2. Acetyl CoA carboxylation to malonyl CoA (via acetyl CoA carboxylase with biotin) [+ insulin, citrate]
3. Assembly of palmitate (via fatty acid synthase and Vit B5)
2097
Steps in palmitate assembly
1. Condensation
2. Reduction
3. Dehydration
4. Reduction
2098
What is the fate of Palmitate after its production?
1. Further elongation in SER and mitochondria
| 2. Desaturated in the ER (but not past the 9th carbon)
2099
Main storage form of fatty acids
Triacylglycerols
2100
Where does TAG synthesis occur?
Liver and adipose tissue
2101
Sources of glycerol-3-phosphate
1. DHAP from glycolysis (liver and adipose)
| 2. Phosphorylation of free glycerol (liver)
2102
What enzyme is responsible for the release of free fatty acids from TAGs?
Hormone sensitive lipases
2103
In the bloodstream fatty acids are always bound to?
Albumin
2104
Hormone sensitive lipases can only release what free fatty acids stored in TAG?
C1 & 3 thus resulting in
TAG -> 2 free FA and 2-mono acyl glycerol
2105
Where does B-oxidation of fatty acids occur
Mitochondria of all cells, but the fatty acid activation raft occurs in the Cytosol
Exception: RBC, kidney medulla, neurons, testes
2106
Rate limiting step in B-oxidation
Fatty acyl CoA + carnitine -> fatty acyl carnitine + CoA
| Enzyme: carnitine acyl transferase I
2107
Cutoff number of carbons that do not need a shuttle
Less than 12 carbons
2108
Steps in the carnitine shuttle
1. Fatty acyl synthase activates the fatty acid
2. Carnitine acyl transferase 1 attaches to fatty acyl to carnitine in the outer mitochondrial membrane
3. Fatty acyl-carnitine is shuttle through the inner membrane
4. Carnitine acyl transferase-2 transfers fatty acyl group back to a CoA in the mitochondrial matrix
2109
Steps in beta oxidation
1. Oxidation
2. Hydratiion
3. Oxidation
4. Thiolysis
2110
Beta oxidation of fatty acids with an odd number of carbon atoms releases?
Propionyl CoA which is converted to methylmalonyl coa (requires B12) then to succinyl CoA
2111
Which is responsible for the conversion of very long chain fatty acids?
Peroxisomes but if unsaturated it requires 3,2 enol-CoA isomerase
2112
Energy yield in ATP of beta oxidation of palmitate
129 ATP
7 NADH= 21
7 FAD= 14
8 acetyl CoA= 96
Activation = -2
2113
Intake of this compound depletes the body's NAD+ supply leading to accumulation Of fat in the liver
Alcohol
2114
Type of carnitine deficiency which leads to impaired FA oxidation and ketogenesis with hypoglycemia?
CPT-1 deficiency
2115
Type of carnitine deficiency which affects skeletal muscle and when severe the liver
CPT-2 deficiency
2116
It is a disorder school results in decreased fatty acid oxidation. Without the ATP to support gluconeogenesis, hypoglycemia becomes profound which may eventually leads to SIDS. It is prevented by frequent feeding with high carbohydrate and low fat diet.
Medium-chain fatty acyl-CoA dehydrogenase (MCAD) deficiency
2117
Associated with eating unripe fruit of the akee tree which contains hypoglycin thus activating MC and SC acyl CoA dehydrogenase
Jamaican vomiting sickness
2118
Rare neurological disorder which results to the accumulation of phytanic acid found in plant food stuff which blocks Boxidation
Refsum disease
2119
Cerebrohepatorenal syndrome resulting from the absence of peroxisomes in all tissues, it is characterized by liver dysfunction, jaundice, MR, weakness, hypotonia, and craniofacial dimorphism
Zellweger syndrome
2120
Defect in peroxismal activation of VLCFA thus leading to its accumulation. Ssx: apathy, behavral change, then visual loss spasticity, ataxia. All due to the fact since VLCFA are found in myelin tissue.
X-lied adrenoleukodystrophy
2121
Where does ketogenesis occur?
Liver mitochondria
2122
Products of ketogenesis
Acetoacetate and B-hydroxybutyrate (fuel)
| Acetone (cannot be used as fuel)
2123
Rate limiting step of ketogenesis
Acetoacetyl CoA + acetyl CoA --(HMG CoA synthase)--> HMG CoA
2124
What are the initial products that lead to the formation of acetyl CoA in ketogenolysis?
B-hydroxybutyrate -> acetoacetate -> acetyl coa
2125
What peripheral tissues can oxidize ketone bodes?
Those with mitochondria like the renal cortex, brain, and skeletal muscle
2126
Why cant liver convert acetoacetate to acetyl CoA?
It lacks succinyl-CoA acetoacetyl-CoA reductase (thiophorase)
2127
What is the Urine test for ketones? What ketone type does not it detect?
Nitroprusside test
Does not detect b-hydroxybutyrate
2128
Which part of cholesterol can a fatty acid attach to form a cholesteryl ester?
Single hydroxyl group of carbon 3 of the alpha ring
2129
Where does cholesterol synthesis occur?
All cells in the Cytosol and SER majority of which are found in the liver and intestines
2130
Substrates of cholesterol synthesis
Acetyl CoA, NADPH, ATP
2131
Rate limiting step in cholesterol synthesis
HMG CoA --(HMG CoA reductase)--> mevalonate
2132
Steps in Cholestid synthesis
1. Biosynthesis of mevalonate
2. Formation of isoprenoid units
3. Isoprene unit is formed from 6 isoprenoid units
4. Formation of lanosterol
5. Formation of cholesterol
2133
How is the cholesterol ring eliminated?
Through conversion to bile salts then secretion to bile
2134
Bile acid synthesis, found in the liver and Cytosol, rate limiting enzyme is?
Cholesterol-7-a-hydroxylase
2135
What are the primary bile acids?
Cholic acid
| Chenocholic acid
2136
What are the two amino acids used in bile acid conjugation to form bile salts?
Taurine and glycine
2137
What are the secondary bile acids?
Deoxycholic acid
| Lithocholic acid
2138
Where does steroid hormone synthesis occur?
SER of the adrenal glands, ovaries and testes, and placenta
2139
What is blocked by the drug aminogluthetimide?
The conversion of cholesterol to pregnenolone by desmolase
2140
The enzyme responsible for the breakdown of TAG to FA and:
A) 2-MAG from diet
B) FREE glycerol from chylomicrons and VLDL
C) 2-MAG from adipose
A) pancreatic lipase
B) Lipoprotein lipase
C) hormone sensitive lipase
2141
Lipoprotein with the largest percentage of TG
Chylomicrons
2142
Lipoprotein with the largest percentage of cholesteryl esters
LDL
2143
Chylomicrons transport TG and cholesterol from where to where?
Intestines to tissues
2144
VLDL transports TG from where to where?
Liver to tissues
2145
What apoprotein activates lipoprotein lipase?
APO-CII
2146
What apolipoprotein uptakes remnants by the liver?
APO E
2147
Apolipoprotein B-48 is used by chylomicrons which are created by the?
Epithelial cells
2148
What apolipoprotein is secreted by the liver for VDL?
B-100
2149
How does IDL become LDL?
By picking up cholesterol from HD!
2150
Which apoprotein delivers cholesterol into cells?
LDL
2151
Which apolipoprotein is used by HDL to activate lecithin cholesterol acyl transferase or LCAT to produce cholesterol esters?
APO-A1
2152
Difference between Type II familial hypercholesterolemia and type IV familial hypertriglyceredemia?
The former has high LDL leader to xanthomas and xanthelasmas with increased risk of atherosclerosis and CHD
The latter has increased VLDL production leading to a triad of
1. DM type 2
2. CAD
3. Obesity
2153
Phospholipid is composed of
DAG
Alcohol
Phosphodiester bond
2154
Most abundant phospholipid which is important in nervous transmission
Phosphatidylcholine
2155
Phospholipid playing a role in apoptosis
Phosphatidyl serine
2156
Phospholipid that is a major component of surfactant?
Dipalmitoylphosphatidylcholine
2157
Phospholipid reservoir for arachidonic acid in the membranes
Phosphatidylinositol
2158
What phospholipid is essential in mitochondrial function which is also used as a non-troponemal test due to its ability to act as an antigen?
Cardiolipin
2159
```
Composition of these glycolipids:
Ceramide
Cerebroside
Globoside
Ganglioside
Sulfatide
```
Ceramide: sphingosine + FA
```
Ceramide + ________
Glucose or galactose = Cerebroside
Oligosacchardide = Globoside
N-acetylneuramic acid = Ganglioside
Sulfated galactose = Sulfatide
```
2160
Hexosaminidase a ficiency leading to Ssx like cherry red macula, MR, hypotonia
Tay-Sachs disease
2161
A-galactosidase deficiency leading to 3Rs: recessive x-linked, rash, renal failure
Fabrys disease
2162
B-glucosidase deficiency leading to hepatosplenomegaly and erosion of long bones
Gauchers dissease
2163
Sphingomyelinase deficiency leading to hepatosplenomegaly
Nieman-pick disease
2164
The set of all proteins expressed by an individual at a particular time
Proteome
2165
Aims to identify the entire complement of proteins elaborated by a cell under diverse conditions
Proteomics
2166
What amino acid is needed to form ALA in heme synthesis?
Glycine combined with succinyl CoA
2167
Which amino acid carries nitrogen from the liver?
Alanine
2168
Which amino acids are implicated in maple syrup disease
valine, lucine, isoleucine
2169
What enzyme is responsible for the buildup of phenyl lactate, phenyl acetate, and phenylpyruvate?
Phenylalanine hydroxylase
2170
What amino acid is the precursor for niacin, serotonin, and melatonin?
Serotonin
2171
What is the amino acid precursor for homocysteine?
Methionine
2172
What amino acid contributes to the fibrous structure of collagen and interrupts a-helices in globular proteins?
Proline
2173
Increase of the combination of this Amino acid is responsible for the curly hair of people?
Cysteine + cysteine = cystine
2174
Amino acids with sites for O-linked glycosylation in the Golgi apparatus?
Serine and threonine
2175
Site for n-linked glycosylation in the ER
Asparagine
2176
Amino acid deaminated by an enzyme which results in the formation of ammonia. This is the major carrier of nitrogen to the liver from peripheral tissues,
Glutaminase deaminates glutamine
2177
Amino acid used in the determination for Folic acid deficiency. What is the test called?
Histidine used in the N-forminoglutamate excretion test
| Increased amounts of FIGu in urine by Folic acid deficient individuals after histindine intake
2178
Precursor amino acid for creatinine, urea, nitric oxide
Arginine
2179
Essential amino acids that cannot be synthesized by the body and must come from the diet
PVT TIM HALL always ARGues and never TYRes
Phenylalanine, valine, tryptophan, threonine' isoleucine, methionine, histidine, argenine, Leucine, Lysine
2180
Heme is a complex of?
Protoporphorin IX and heme
2181
What is the Bohr effect?
HBO2 + H+ HbH + O2
2182
What is an oxidized for of HB (Fe 3+) that does not bind O2 readily which could lead to chocolate cyanosis ? It is treated with oral methylene blue or ascorbic acid up to IV methylene blue.
Methemoglobin
2183
Hemoglobin bound to carbon monoxide instead of O2 leading to a cherry pink color.
Carboxyhemoglobin
2184
HB bound to carbon dioxide is called
Carbaminohenoglobin
2185
Classification of alpha and beta thalassemia
Alpha: silent carrier, a-thalassemia trait, Hb H disease, hydrops fetalis
Beta: B-thalassemia minor and major
2186
Most frequently affected collagen in Ehler Danlos syndrome leading to hyper extensible skin, tendency to bleed, hyper mobile joints, and increased risk for berry aneurysms.
Collagen type 3
2187
Collagen I mutation leading to bendable and easily fractured bones. Accompanied with blue sclerae, hearing loss, and dental imperfections.
Osteogenesis imperfecta
2188
Vitamin C deficiency leading to decreased hydroxylation of collagen. This leads to sore spongy gums, loose teeth, poor wound healing, and petecchiae on skin and mucous membranes.
Scurvy
2189
Type IV collagen defect leading to hematuria and ESRD
Alpert syndrome
2190
Collagen defect leading to kinky hair due to a deficiency of copper required by lysyl oxidase to strengthen collagen fibers.
Menke syndrome
2191
Skin breaking and blisters as a result for minor trauma. This disease is due to a defect in collage VII.
Epidermolysis bullosa
2192
Like collagen elastin has pro line and Lysine but has little and no?
Hydroxyproline
| Hydroxylysine
2193
Protein degradation mechanisms of nitrogen
Energy dependent ubiquitin-proteosome mechanism
| Non-energy dependent degradation enzyme
2194
Phases in amino acid catabolism
First phase: removal of a-amino group forming ammonia and a corresponding ketoacid
Second phase: carbon skeletons of a-ketoacids are converted to common intermediates of energy producing metabolic pathwas
2195
Two main steps in nitrogen removal from AA
1. Transamination
| 2. Oxidative deamination
2196
Where does transamination occur?
All cells of the body
2197
All but two amino acids transfer their amino groups to a-ketoglutarate except?
Lysine and threonine
2198
What is the coenzyme for the two aminotransferases?
Pyridoxal phosphate (vitamin B6)
2199
Oxidative deamination occurs where and for which amino acid only?
Liver and kidney
| Only glutamate
2200
Glutamate is oxidized by glutamate dehydrogenases and deaminated to form ?
free ammonia which is used to make urea
2201
What does the conversion of glutamate to a-ketoglutarate yield? What about vice versa?
Glutamate -> a ketoglutarate NH3 + NADH
| A ketoglutarate -> glutamate NADP+ + NH3
2202
How is excess nitrogen removal from peripheral tissues removed?
1. Glutamine: via glutamate + ammonia (through Flutamide synthaetase)
2. Alanine: via glucose -> pyruvate + glutamate -> alanine cycle
2203
Glutaminase deaminates glutamine to produce ammonium ion which is excreted from the body. Where are the two tissues this enzyme could be located?
Kidneys and small intestines
2204
Another name for urea cycle
Ornithine cycle or krebs-henseleit cycle
2205
What are the donors of the urea molecule?
1. NH3 from free ammonia
2. NH3 from aspartate
3. 1C and 1O from CO2
2206
Reactions in the urea cycle
1. Formation of carbamoyl phosphate (via carbamoyl phosphate synthetase I)
2. Formation of citrulline (via Ornithine transcarbamoylase)
3. Synthesis of arginosuccinate (arginosuccinate synthetase)
4. Cleavage of arginosuccinate to form arginine (Arginosuccinase)
5. Arginine cleavage to yield urea and Ornithine (arginase)
2207
Rate limiting step of urea cycle
Carbamoyl phosphate synthetase I
2208
Energy requirement of urea cycle
4 ATP
2209
Co factors of urea cycle
N-acetylglutamate
| Biotin
2210
Hereditary hyperammonemia produces symptoms such as
Hyperammonemia, elevated blood glutamine, decreased BUN
| Parents with lethargy, vomiting, hyperventilation, convulsions, cerebral edema, coma, and death
2211
Treatment for hereditary hyperammonemia
Low protein diet
| Administration of sodium benzoate or phenylpyruvate to capture and excrete excess nitrogen
2212
Ketogenic carbon skeletons of AA
Leucine
Lysine
Yields acetoacetate or acetyl-coa/ acetoacetyl-coa
2213
Ketogenic and glucogenic carbon skeletons of AA
```
WIFY
Phenylalanine
Isoleucine
Tryptophan
Tyrosine
```
Yields Ketogenic and glucose or glycogen by products
2214
This amino acid acts as a raw material in the biosynthesis of Heme, purines, creatine
Glycine
2215
This amino acid acts as a raw material in the biosynthesis of phospholipid, sphingolipid, purines, thymine
Serine
2216
This amino acid acts as a raw material in the biosynthesis of GABA
Glutamate
2217
This amino acid acts as a raw material in the biosynthesis of creatine, polyamines, nitric oxide
Arginine
2218
This amino acid acts as a raw material in the biosynthesis of serotonin, NAD+, NADP+, melatonin
Tryptophan
2219
This amino acid acts as a raw material in the biosynthesis of catecholamines, thyroid hormones, melanin
Tyrosine
2220
3 hormones dependent on tyrosine
Thyroid hormones
Melanin
Catecholamines
2221
Deficiency of homogenistic acid oxidase in the degrative pathway of tyrosine which results in urine turning to black on standing with dark connective tissues (ochronosis)
Alkaptonuria
2222
Congenital deficiency due tyrosinase deficieny or defective tyrosine transporters which leads to an increased risk for skin cancer.
Albinism
2223
Autosomal recessive disorder that may either be due to decreased methionine, increased cysteine, B6, and folate or decreased affinity for cystathione synthase. This results in mental retardation, osteoporosis, tall stature, lens subluxation, and atherosclerosis.
Homocystinuria
2224
Common inherited defect of renal tubular amino acid transporter for its parent compound, Ornithine, Lysine, and arginine, in the PCT of the kidneys. It eventually precipitates and cause staghorn caliculi. What is its treatment?
Cystinuria is treated with acetazolamide to alkalinize the urine
2225
The initial and last three steps of heme synthesis occurs in?
The mitochondria
2226
Heme synthesis summary
1. Formation of ALA (via ALA synthase and B6)
2. Formation of porphobilinogen
3. Formation of uroporphyrinogen
4. Formation of heme
2227
Lead inhibits what two steps in heme synthesis?
1. Introduction of Fe 2+ into protoporphyrin IX via ferrochelatase
2. Condensation of two ALA molecules by zinc containing ALA dehydratase
2228
Where is B6 a cofactors of?
1. Heme synthesis
2. Synthesis of cystathionine from homocysteine
3. Transamination between alanine and a-ketoglutarate
2229
Most common porphyria
Porphyria cutanea tarda
2230
Which part of heme synthesis do these symptoms appear?
1. Photosensitivity
2. Neuropsychiatric symptoms
1. After ring formation
| 2. Before ring formation
2231
Pyridoxine ficiency associated with isoniazid therapy results in this histopathologic finding
Sideroblastic anemia with ringed sideroblast
2232
Poisoning due to this heavy metal leads to coar basophilic stippling of RBC, peripheral neuropathy, lines in gums, increas in urinary ALA and free erythrocytes porphorin
lead poisoning
2233
Microcytic hypo chromic anemia is found in
IDA
Thalassemia
Lead poisoning
2234
Megaloblastic anemia is found in
Folate or B12 deficiency
| Pernicious anemia
2235
Normoyctic normochromic anemia is found in
Anemia of chronic kidney disease
| Blood loss
2236
Increase in MCHC is found in
Hereditary spherocytosis
2237
Summary of heme degradation
1. Formation of bilirubin
2. Uptake of bilirubin by the liver
3. Formation of bilirubin diglucoronide
4. Secretion of bilirubin into bile
5. Formation of urobilins in the intestine
2238
Colors of biliverdin, bilirubin, urobilinogen, stercolin, urobilin
```
Biliverdin: green
Bilirubin: red orange
Urobilinogen: colorless
Stercolin: brown orange red
Urobilin: yellow
```
2239
Examples of unconjugated hyperbilirubinemia
```
Hemolytic anemia
Physiologic jaundice
Crigler-najjar syndrome types I and II
Gilbert syndrome
Toxic hyperbilirubinemia
```
2240
Examples of conjugated hyperbilirubinemia
Biliary tree obstruction
Dubin-Johnson syndrome
Rotor syndrome
2241
What reaction measures total and direct bilirubin?
Van den bergs reaction
2242
What enzyme activates fatty acid for metabolism use?
Fatty-acyl-CoA synthetase
2243
Cofactor required for fatty acid activation
Vitamin B5 or Panthotenic acid
2244
Energy required to activate fatty acid
2 ATP
2245
What is the product formed in fatty acid synthesis?
Palmitate (16:0)
2246
Where does fatty acid synthesis occur?
Cytosol
Major: Liver and lactating mammary glands
Minor: adipose tissue
2247
Substrates for fatty acid synthesis
1 acetyl CoA
7 malonyl CoA
NADPH
ATP
2248
Rate limiting step in fatty acid synthesis
Acetyl CoA + ATP -> malonyl CoA
| Enzyme: acetyl CoA carboxylase
2249
Steps in fatty acid synthesis
1. Synthesis of cytoplasmic acetyl CoA (transfer of mitochondrial acetyl CoA to cytoplasm via citrate shuttle)
2. Acetyl CoA carboxylation to malonyl CoA (via acetyl CoA carboxylase with biotin) [+ insulin, citrate]
3. Assembly of palmitate (via fatty acid synthase and Vit B5)
2250
Steps in palmitate assembly
1. Condensation
2. Reduction
3. Dehydration
4. Reduction
2251
What is the fate of Palmitate after its production?
1. Further elongation in SER and mitochondria
| 2. Desaturated in the ER (but not past the 9th carbon)
2252
Main storage form of fatty acids
Triacylglycerols
2253
Where does TAG synthesis occur?
Liver and adipose tissue
2254
Sources of glycerol-3-phosphate
1. DHAP from glycolysis (liver and adipose)
| 2. Phosphorylation of free glycerol (liver)
2255
What enzyme is responsible for the release of free fatty acids from TAGs?
Hormone sensitive lipases
2256
In the bloodstream fatty acids are always bound to?
Albumin
2257
Hormone sensitive lipases can only release what free fatty acids stored in TAG?
C1 & 3 thus resulting in
TAG -> 2 free FA and 2-mono acyl glycerol
2258
Where does B-oxidation of fatty acids occur
Mitochondria of all cells, but the fatty acid activation raft occurs in the Cytosol
Exception: RBC, kidney medulla, neurons, testes
2259
Rate limiting step in B-oxidation
Fatty acyl CoA + carnitine -> fatty acyl carnitine + CoA
| Enzyme: carnitine acyl transferase I
2260
Cutoff number of carbons that do not need a shuttle
Less than 12 carbons
2261
Steps in the carnitine shuttle
1. Fatty acyl synthase activates the fatty acid
2. Carnitine acyl transferase 1 attaches to fatty acyl to carnitine in the outer mitochondrial membrane
3. Fatty acyl-carnitine is shuttle through the inner membrane
4. Carnitine acyl transferase-2 transfers fatty acyl group back to a CoA in the mitochondrial matrix
2262
Steps in beta oxidation
1. Oxidation
2. Hydratiion
3. Oxidation
4. Thiolysis
2263
Beta oxidation of fatty acids with an odd number of carbon atoms releases?
Propionyl CoA which is converted to methylmalonyl coa (requires B12) then to succinyl CoA
2264
Which is responsible for the conversion of very long chain fatty acids?
Peroxisomes but if unsaturated it requires 3,2 enol-CoA isomerase
2265
Energy yield in ATP of beta oxidation of palmitate
129 ATP
7 NADH= 21
7 FAD= 14
8 acetyl CoA= 96
Activation = -2
2266
Intake of this compound depletes the body's NAD+ supply leading to accumulation Of fat in the liver
Alcohol
2267
Type of carnitine deficiency which leads to impaired FA oxidation and ketogenesis with hypoglycemia?
CPT-1 deficiency
2268
Type of carnitine deficiency which affects skeletal muscle and when severe the liver
CPT-2 deficiency
2269
It is a disorder school results in decreased fatty acid oxidation. Without the ATP to support gluconeogenesis, hypoglycemia becomes profound which may eventually leads to SIDS. It is prevented by frequent feeding with high carbohydrate and low fat diet.
Medium-chain fatty acyl-CoA dehydrogenase (MCAD) deficiency
2270
Associated with eating unripe fruit of the akee tree which contains hypoglycin thus activating MC and SC acyl CoA dehydrogenase
Jamaican vomiting sickness
2271
Rare neurological disorder which results to the accumulation of phytanic acid found in plant food stuff which blocks Boxidation
Refsum disease
2272
Cerebrohepatorenal syndrome resulting from the absence of peroxisomes in all tissues, it is characterized by liver dysfunction, jaundice, MR, weakness, hypotonia, and craniofacial dimorphism
Zellweger syndrome
2273
Defect in peroxismal activation of VLCFA thus leading to its accumulation. Ssx: apathy, behavral change, then visual loss spasticity, ataxia. All due to the fact since VLCFA are found in myelin tissue.
X-lied adrenoleukodystrophy
2274
Where does ketogenesis occur?
Liver mitochondria
2275
Products of ketogenesis
Acetoacetate and B-hydroxybutyrate (fuel)
| Acetone (cannot be used as fuel)
2276
Rate limiting step of ketogenesis
Acetoacetyl CoA + acetyl CoA --(HMG CoA synthase)--> HMG CoA
2277
What are the initial products that lead to the formation of acetyl CoA in ketogenolysis?
B-hydroxybutyrate -> acetoacetate -> acetyl coa
2278
What peripheral tissues can oxidize ketone bodes?
Those with mitochondria like the renal cortex, brain, and skeletal muscle
2279
Why cant liver convert acetoacetate to acetyl CoA?
It lacks succinyl-CoA acetoacetyl-CoA reductase (thiophorase)
2280
What is the Urine test for ketones? What ketone type does not it detect?
Nitroprusside test
Does not detect b-hydroxybutyrate
2281
Which part of cholesterol can a fatty acid attach to form a cholesteryl ester?
Single hydroxyl group of carbon 3 of the alpha ring
2282
Where does cholesterol synthesis occur?
All cells in the Cytosol and SER majority of which are found in the liver and intestines
2283
Substrates of cholesterol synthesis
Acetyl CoA, NADPH, ATP
2284
Rate limiting step in cholesterol synthesis
HMG CoA --(HMG CoA reductase)--> mevalonate
2285
Steps in Cholestid synthesis
1. Biosynthesis of mevalonate
2. Formation of isoprenoid units
3. Isoprene unit is formed from 6 isoprenoid units
4. Formation of lanosterol
5. Formation of cholesterol
2286
How is the cholesterol ring eliminated?
Through conversion to bile salts then secretion to bile
2287
Bile acid synthesis, found in the liver and Cytosol, rate limiting enzyme is?
Cholesterol-7-a-hydroxylase
2288
What are the primary bile acids?
Cholic acid
| Chenocholic acid
2289
What are the two amino acids used in bile acid conjugation to form bile salts?
Taurine and glycine
2290
What are the secondary bile acids?
Deoxycholic acid
| Lithocholic acid
2291
Where does steroid hormone synthesis occur?
SER of the adrenal glands, ovaries and testes, and placenta
2292
What is blocked by the drug aminogluthetimide?
The conversion of cholesterol to pregnenolone by desmolase
2293
The enzyme responsible for the breakdown of TAG to FA and:
A) 2-MAG from diet
B) FREE glycerol from chylomicrons and VLDL
C) 2-MAG from adipose
A) pancreatic lipase
B) Lipoprotein lipase
C) hormone sensitive lipase
2294
Lipoprotein with the largest percentage of TG
Chylomicrons
2295
Lipoprotein with the largest percentage of cholesteryl esters
LDL
2296
Chylomicrons transport TG and cholesterol from where to where?
Intestines to tissues
2297
VLDL transports TG from where to where?
Liver to tissues
2298
What apoprotein activates lipoprotein lipase?
APO-CII
2299
What apolipoprotein uptakes remnants by the liver?
APO E
2300
Apolipoprotein B-48 is used by chylomicrons which are created by the?
Epithelial cells
2301
What apolipoprotein is secreted by the liver for VDL?
B-100
2302
How does IDL become LDL?
By picking up cholesterol from HD!
2303
Which apoprotein delivers cholesterol into cells?
LDL
2304
Which apolipoprotein is used by HDL to activate lecithin cholesterol acyl transferase or LCAT to produce cholesterol esters?
APO-A1
2305
Difference between Type II familial hypercholesterolemia and type IV familial hypertriglyceredemia?
The former has high LDL leader to xanthomas and xanthelasmas with increased risk of atherosclerosis and CHD
The latter has increased VLDL production leading to a triad of
1. DM type 2
2. CAD
3. Obesity
2306
Phospholipid is composed of
DAG
Alcohol
Phosphodiester bond
2307
Most abundant phospholipid which is important in nervous transmission
Phosphatidylcholine
2308
Phospholipid playing a role in apoptosis
Phosphatidyl serine
2309
Phospholipid that is a major component of surfactant?
Dipalmitoylphosphatidylcholine
2310
Phospholipid reservoir for arachidonic acid in the membranes
Phosphatidylinositol
2311
What phospholipid is essential in mitochondrial function which is also used as a non-troponemal test due to its ability to act as an antigen?
Cardiolipin
2312
```
Composition of these glycolipids:
Ceramide
Cerebroside
Globoside
Ganglioside
Sulfatide
```
Ceramide: sphingosine + FA
```
Ceramide + ________
Glucose or galactose = Cerebroside
Oligosacchardide = Globoside
N-acetylneuramic acid = Ganglioside
Sulfated galactose = Sulfatide
```
2313
Hexosaminidase a ficiency leading to Ssx like cherry red macula, MR, hypotonia
Tay-Sachs disease
2314
A-galactosidase deficiency leading to 3Rs: recessive x-linked, rash, renal failure
Fabrys disease
2315
B-glucosidase deficiency leading to hepatosplenomegaly and erosion of long bones
Gauchers dissease
2316
Sphingomyelinase deficiency leading to hepatosplenomegaly
Nieman-pick disease
2317
The set of all proteins expressed by an individual at a particular time
Proteome
2318
Aims to identify the entire complement of proteins elaborated by a cell under diverse conditions
Proteomics
2319
What amino acid is needed to form ALA in heme synthesis?
Glycine combined with succinyl CoA
2320
Which amino acid carries nitrogen from the liver?
Alanine
2321
Which amino acids are implicated in maple syrup disease
valine, lucine, isoleucine
2322
What enzyme is responsible for the buildup of phenyl lactate, phenyl acetate, and phenylpyruvate?
Phenylalanine hydroxylase
2323
What amino acid is the precursor for niacin, serotonin, and melatonin?
Serotonin
2324
What is the amino acid precursor for homocysteine?
Methionine
2325
What amino acid contributes to the fibrous structure of collagen and interrupts a-helices in globular proteins?
Proline
2326
Increase of the combination of this Amino acid is responsible for the curly hair of people?
Cysteine + cysteine = cystine
2327
Amino acids with sites for O-linked glycosylation in the Golgi apparatus?
Serine and threonine
2328
Site for n-linked glycosylation in the ER
Asparagine
2329
Amino acid deaminated by an enzyme which results in the formation of ammonia. This is the major carrier of nitrogen to the liver from peripheral tissues,
Glutaminase deaminates glutamine
2330
Amino acid used in the determination for Folic acid deficiency. What is the test called?
Histidine used in the N-forminoglutamate excretion test
| Increased amounts of FIGu in urine by Folic acid deficient individuals after histindine intake
2331
Precursor amino acid for creatinine, urea, nitric oxide
Arginine
2332
Essential amino acids that cannot be synthesized by the body and must come from the diet
PVT TIM HALL always ARGues and never TYRes
Phenylalanine, valine, tryptophan, threonine' isoleucine, methionine, histidine, argenine, Leucine, Lysine
2333
Heme is a complex of?
Protoporphorin IX and heme
2334
What is the Bohr effect?
HBO2 + H+ HbH + O2
2335
What is an oxidized for of HB (Fe 3+) that does not bind O2 readily which could lead to chocolate cyanosis ? It is treated with oral methylene blue or ascorbic acid up to IV methylene blue.
Methemoglobin
2336
Hemoglobin bound to carbon monoxide instead of O2 leading to a cherry pink color.
Carboxyhemoglobin
2337
HB bound to carbon dioxide is called
Carbaminohenoglobin
2338
Classification of alpha and beta thalassemia
Alpha: silent carrier, a-thalassemia trait, Hb H disease, hydrops fetalis
Beta: B-thalassemia minor and major
2339
Most frequently affected collagen in Ehler Danlos syndrome leading to hyper extensible skin, tendency to bleed, hyper mobile joints, and increased risk for berry aneurysms.
Collagen type 3
2340
Collagen I mutation leading to bendable and easily fractured bones. Accompanied with blue sclerae, hearing loss, and dental imperfections.
Osteogenesis imperfecta
2341
Vitamin C deficiency leading to decreased hydroxylation of collagen. This leads to sore spongy gums, loose teeth, poor wound healing, and petecchiae on skin and mucous membranes.
Scurvy
2342
Type IV collagen defect leading to hematuria and ESRD
Alpert syndrome
2343
Collagen defect leading to kinky hair due to a deficiency of copper required by lysyl oxidase to strengthen collagen fibers.
Menke syndrome
2344
Skin breaking and blisters as a result for minor trauma. This disease is due to a defect in collage VII.
Epidermolysis bullosa
2345
Like collagen elastin has pro line and Lysine but has little and no?
Hydroxyproline
| Hydroxylysine
2346
Protein degradation mechanisms of nitrogen
Energy dependent ubiquitin-proteosome mechanism
| Non-energy dependent degradation enzyme
2347
Phases in amino acid catabolism
First phase: removal of a-amino group forming ammonia and a corresponding ketoacid
Second phase: carbon skeletons of a-ketoacids are converted to common intermediates of energy producing metabolic pathwas
2348
Two main steps in nitrogen removal from AA
1. Transamination
| 2. Oxidative deamination
2349
Where does transamination occur?
All cells of the body
2350
All but two amino acids transfer their amino groups to a-ketoglutarate except?
Lysine and threonine
2351
What is the coenzyme for the two aminotransferases?
Pyridoxal phosphate (vitamin B6)
2352
Oxidative deamination occurs where and for which amino acid only?
Liver and kidney
| Only glutamate
2353
Glutamate is oxidized by glutamate dehydrogenases and deaminated to form ?
free ammonia which is used to make urea
2354
What does the conversion of glutamate to a-ketoglutarate yield? What about vice versa?
Glutamate -> a ketoglutarate NH3 + NADH
| A ketoglutarate -> glutamate NADP+ + NH3
2355
How is excess nitrogen removal from peripheral tissues removed?
1. Glutamine: via glutamate + ammonia (through Flutamide synthaetase)
2. Alanine: via glucose -> pyruvate + glutamate -> alanine cycle
2356
Glutaminase deaminates glutamine to produce ammonium ion which is excreted from the body. Where are the two tissues this enzyme could be located?
Kidneys and small intestines
2357
Another name for urea cycle
Ornithine cycle or krebs-henseleit cycle
2358
What are the donors of the urea molecule?
1. NH3 from free ammonia
2. NH3 from aspartate
3. 1C and 1O from CO2
2359
Reactions in the urea cycle
1. Formation of carbamoyl phosphate (via carbamoyl phosphate synthetase I)
2. Formation of citrulline (via Ornithine transcarbamoylase)
3. Synthesis of arginosuccinate (arginosuccinate synthetase)
4. Cleavage of arginosuccinate to form arginine (Arginosuccinase)
5. Arginine cleavage to yield urea and Ornithine (arginase)
2360
Rate limiting step of urea cycle
Carbamoyl phosphate synthetase I
2361
Energy requirement of urea cycle
4 ATP
2362
Co factors of urea cycle
N-acetylglutamate
| Biotin
2363
Hereditary hyperammonemia produces symptoms such as
Hyperammonemia, elevated blood glutamine, decreased BUN
| Parents with lethargy, vomiting, hyperventilation, convulsions, cerebral edema, coma, and death
2364
Treatment for hereditary hyperammonemia
Low protein diet
| Administration of sodium benzoate or phenylpyruvate to capture and excrete excess nitrogen
2365
Ketogenic carbon skeletons of AA
Leucine
Lysine
Yields acetoacetate or acetyl-coa/ acetoacetyl-coa
2366
Ketogenic and glucogenic carbon skeletons of AA
```
WIFY
Phenylalanine
Isoleucine
Tryptophan
Tyrosine
```
Yields Ketogenic and glucose or glycogen by products
2367
This amino acid acts as a raw material in the biosynthesis of Heme, purines, creatine
Glycine
2368
This amino acid acts as a raw material in the biosynthesis of phospholipid, sphingolipid, purines, thymine
Serine
2369
This amino acid acts as a raw material in the biosynthesis of GABA
Glutamate
2370
This amino acid acts as a raw material in the biosynthesis of creatine, polyamines, nitric oxide
Arginine
2371
This amino acid acts as a raw material in the biosynthesis of serotonin, NAD+, NADP+, melatonin
Tryptophan
2372
This amino acid acts as a raw material in the biosynthesis of catecholamines, thyroid hormones, melanin
Tyrosine
2373
3 hormones dependent on tyrosine
Thyroid hormones
Melanin
Catecholamines
2374
Deficiency of homogenistic acid oxidase in the degrative pathway of tyrosine which results in urine turning to black on standing with dark connective tissues (ochronosis)
Alkaptonuria
2375
Congenital deficiency due tyrosinase deficieny or defective tyrosine transporters which leads to an increased risk for skin cancer.
Albinism
2376
Autosomal recessive disorder that may either be due to decreased methionine, increased cysteine, B6, and folate or decreased affinity for cystathione synthase. This results in mental retardation, osteoporosis, tall stature, lens subluxation, and atherosclerosis.
Homocystinuria
2377
Common inherited defect of renal tubular amino acid transporter for its parent compound, Ornithine, Lysine, and arginine, in the PCT of the kidneys. It eventually precipitates and cause staghorn caliculi. What is its treatment?
Cystinuria is treated with acetazolamide to alkalinize the urine
2378
The initial and last three steps of heme synthesis occurs in?
The mitochondria
2379
Heme synthesis summary
1. Formation of ALA (via ALA synthase and B6)
2. Formation of porphobilinogen
3. Formation of uroporphyrinogen
4. Formation of heme
2380
Lead inhibits what two steps in heme synthesis?
1. Introduction of Fe 2+ into protoporphyrin IX via ferrochelatase
2. Condensation of two ALA molecules by zinc containing ALA dehydratase
2381
Where is B6 a cofactors of?
1. Heme synthesis
2. Synthesis of cystathionine from homocysteine
3. Transamination between alanine and a-ketoglutarate
2382
Most common porphyria
Porphyria cutanea tarda
2383
Which part of heme synthesis do these symptoms appear?
1. Photosensitivity
2. Neuropsychiatric symptoms
1. After ring formation
| 2. Before ring formation
2384
Pyridoxine ficiency associated with isoniazid therapy results in this histopathologic finding
Sideroblastic anemia with ringed sideroblast
2385
Poisoning due to this heavy metal leads to coar basophilic stippling of RBC, peripheral neuropathy, lines in gums, increas in urinary ALA and free erythrocytes porphorin
lead poisoning
2386
Microcytic hypo chromic anemia is found in
IDA
Thalassemia
Lead poisoning
2387
Megaloblastic anemia is found in
Folate or B12 deficiency
| Pernicious anemia
2388
Normoyctic normochromic anemia is found in
Anemia of chronic kidney disease
| Blood loss
2389
Increase in MCHC is found in
Hereditary spherocytosis
2390
Summary of heme degradation
1. Formation of bilirubin
2. Uptake of bilirubin by the liver
3. Formation of bilirubin diglucoronide
4. Secretion of bilirubin into bile
5. Formation of urobilins in the intestine
2391
Colors of biliverdin, bilirubin, urobilinogen, stercolin, urobilin
```
Biliverdin: green
Bilirubin: red orange
Urobilinogen: colorless
Stercolin: brown orange red
Urobilin: yellow
```
2392
Examples of unconjugated hyperbilirubinemia
```
Hemolytic anemia
Physiologic jaundice
Crigler-najjar syndrome types I and II
Gilbert syndrome
Toxic hyperbilirubinemia
```
2393
Examples of conjugated hyperbilirubinemia
Biliary tree obstruction
Dubin-Johnson syndrome
Rotor syndrome
2394
What reaction measures total and direct bilirubin?
Van den bergs reaction
2395
What enzyme activates fatty acid for metabolism use?
Fatty-acyl-CoA synthetase
2396
Cofactor required for fatty acid activation
Vitamin B5 or Panthotenic acid
2397
Energy required to activate fatty acid
2 ATP
2398
What is the product formed in fatty acid synthesis?
Palmitate (16:0)
2399
Where does fatty acid synthesis occur?
Cytosol
Major: Liver and lactating mammary glands
Minor: adipose tissue
2400
Substrates for fatty acid synthesis
1 acetyl CoA
7 malonyl CoA
NADPH
ATP
2401
Rate limiting step in fatty acid synthesis
Acetyl CoA + ATP -> malonyl CoA
| Enzyme: acetyl CoA carboxylase
2402
Steps in fatty acid synthesis
1. Synthesis of cytoplasmic acetyl CoA (transfer of mitochondrial acetyl CoA to cytoplasm via citrate shuttle)
2. Acetyl CoA carboxylation to malonyl CoA (via acetyl CoA carboxylase with biotin) [+ insulin, citrate]
3. Assembly of palmitate (via fatty acid synthase and Vit B5)
2403
Steps in palmitate assembly
1. Condensation
2. Reduction
3. Dehydration
4. Reduction
2404
What is the fate of Palmitate after its production?
1. Further elongation in SER and mitochondria
| 2. Desaturated in the ER (but not past the 9th carbon)
2405
Main storage form of fatty acids
Triacylglycerols
2406
Where does TAG synthesis occur?
Liver and adipose tissue
2407
Sources of glycerol-3-phosphate
1. DHAP from glycolysis (liver and adipose)
| 2. Phosphorylation of free glycerol (liver)
2408
What enzyme is responsible for the release of free fatty acids from TAGs?
Hormone sensitive lipases
2409
In the bloodstream fatty acids are always bound to?
Albumin
2410
Hormone sensitive lipases can only release what free fatty acids stored in TAG?
C1 & 3 thus resulting in
TAG -> 2 free FA and 2-mono acyl glycerol
2411
Where does B-oxidation of fatty acids occur
Mitochondria of all cells, but the fatty acid activation raft occurs in the Cytosol
Exception: RBC, kidney medulla, neurons, testes
2412
Rate limiting step in B-oxidation
Fatty acyl CoA + carnitine -> fatty acyl carnitine + CoA
| Enzyme: carnitine acyl transferase I
2413
Cutoff number of carbons that do not need a shuttle
Less than 12 carbons
2414
Steps in the carnitine shuttle
1. Fatty acyl synthase activates the fatty acid
2. Carnitine acyl transferase 1 attaches to fatty acyl to carnitine in the outer mitochondrial membrane
3. Fatty acyl-carnitine is shuttle through the inner membrane
4. Carnitine acyl transferase-2 transfers fatty acyl group back to a CoA in the mitochondrial matrix
2415
Steps in beta oxidation
1. Oxidation
2. Hydratiion
3. Oxidation
4. Thiolysis
2416
Beta oxidation of fatty acids with an odd number of carbon atoms releases?
Propionyl CoA which is converted to methylmalonyl coa (requires B12) then to succinyl CoA
2417
Which is responsible for the conversion of very long chain fatty acids?
Peroxisomes but if unsaturated it requires 3,2 enol-CoA isomerase
2418
Energy yield in ATP of beta oxidation of palmitate
129 ATP
7 NADH= 21
7 FAD= 14
8 acetyl CoA= 96
Activation = -2
2419
Intake of this compound depletes the body's NAD+ supply leading to accumulation Of fat in the liver
Alcohol
2420
Type of carnitine deficiency which leads to impaired FA oxidation and ketogenesis with hypoglycemia?
CPT-1 deficiency
2421
Type of carnitine deficiency which affects skeletal muscle and when severe the liver
CPT-2 deficiency
2422
It is a disorder school results in decreased fatty acid oxidation. Without the ATP to support gluconeogenesis, hypoglycemia becomes profound which may eventually leads to SIDS. It is prevented by frequent feeding with high carbohydrate and low fat diet.
Medium-chain fatty acyl-CoA dehydrogenase (MCAD) deficiency
2423
Associated with eating unripe fruit of the akee tree which contains hypoglycin thus activating MC and SC acyl CoA dehydrogenase
Jamaican vomiting sickness
2424
Rare neurological disorder which results to the accumulation of phytanic acid found in plant food stuff which blocks Boxidation
Refsum disease
2425
Cerebrohepatorenal syndrome resulting from the absence of peroxisomes in all tissues, it is characterized by liver dysfunction, jaundice, MR, weakness, hypotonia, and craniofacial dimorphism
Zellweger syndrome
2426
Defect in peroxismal activation of VLCFA thus leading to its accumulation. Ssx: apathy, behavral change, then visual loss spasticity, ataxia. All due to the fact since VLCFA are found in myelin tissue.
X-lied adrenoleukodystrophy
2427
Where does ketogenesis occur?
Liver mitochondria
2428
Products of ketogenesis
Acetoacetate and B-hydroxybutyrate (fuel)
| Acetone (cannot be used as fuel)
2429
Rate limiting step of ketogenesis
Acetoacetyl CoA + acetyl CoA --(HMG CoA synthase)--> HMG CoA
2430
What are the initial products that lead to the formation of acetyl CoA in ketogenolysis?
B-hydroxybutyrate -> acetoacetate -> acetyl coa
2431
What peripheral tissues can oxidize ketone bodes?
Those with mitochondria like the renal cortex, brain, and skeletal muscle
2432
Why cant liver convert acetoacetate to acetyl CoA?
It lacks succinyl-CoA acetoacetyl-CoA reductase (thiophorase)
2433
What is the Urine test for ketones? What ketone type does not it detect?
Nitroprusside test
Does not detect b-hydroxybutyrate
2434
Which part of cholesterol can a fatty acid attach to form a cholesteryl ester?
Single hydroxyl group of carbon 3 of the alpha ring
2435
Where does cholesterol synthesis occur?
All cells in the Cytosol and SER majority of which are found in the liver and intestines
2436
Substrates of cholesterol synthesis
Acetyl CoA, NADPH, ATP
2437
Rate limiting step in cholesterol synthesis
HMG CoA --(HMG CoA reductase)--> mevalonate
2438
Steps in Cholestid synthesis
1. Biosynthesis of mevalonate
2. Formation of isoprenoid units
3. Isoprene unit is formed from 6 isoprenoid units
4. Formation of lanosterol
5. Formation of cholesterol
2439
How is the cholesterol ring eliminated?
Through conversion to bile salts then secretion to bile
2440
Bile acid synthesis, found in the liver and Cytosol, rate limiting enzyme is?
Cholesterol-7-a-hydroxylase
2441
What are the primary bile acids?
Cholic acid
| Chenocholic acid
2442
What are the two amino acids used in bile acid conjugation to form bile salts?
Taurine and glycine
2443
What are the secondary bile acids?
Deoxycholic acid
| Lithocholic acid
2444
Where does steroid hormone synthesis occur?
SER of the adrenal glands, ovaries and testes, and placenta
2445
What is blocked by the drug aminogluthetimide?
The conversion of cholesterol to pregnenolone by desmolase
2446
The enzyme responsible for the breakdown of TAG to FA and:
A) 2-MAG from diet
B) FREE glycerol from chylomicrons and VLDL
C) 2-MAG from adipose
A) pancreatic lipase
B) Lipoprotein lipase
C) hormone sensitive lipase
2447
Lipoprotein with the largest percentage of TG
Chylomicrons
2448
Lipoprotein with the largest percentage of cholesteryl esters
LDL
2449
Chylomicrons transport TG and cholesterol from where to where?
Intestines to tissues
2450
VLDL transports TG from where to where?
Liver to tissues
2451
What apoprotein activates lipoprotein lipase?
APO-CII
2452
What apolipoprotein uptakes remnants by the liver?
APO E
2453
Apolipoprotein B-48 is used by chylomicrons which are created by the?
Epithelial cells
2454
What apolipoprotein is secreted by the liver for VDL?
B-100
2455
How does IDL become LDL?
By picking up cholesterol from HD!
2456
Which apoprotein delivers cholesterol into cells?
LDL
2457
Which apolipoprotein is used by HDL to activate lecithin cholesterol acyl transferase or LCAT to produce cholesterol esters?
APO-A1
2458
Difference between Type II familial hypercholesterolemia and type IV familial hypertriglyceredemia?
The former has high LDL leader to xanthomas and xanthelasmas with increased risk of atherosclerosis and CHD
The latter has increased VLDL production leading to a triad of
1. DM type 2
2. CAD
3. Obesity
2459
Phospholipid is composed of
DAG
Alcohol
Phosphodiester bond
2460
Most abundant phospholipid which is important in nervous transmission
Phosphatidylcholine
2461
Phospholipid playing a role in apoptosis
Phosphatidyl serine
2462
Phospholipid that is a major component of surfactant?
Dipalmitoylphosphatidylcholine
2463
Phospholipid reservoir for arachidonic acid in the membranes
Phosphatidylinositol
2464
What phospholipid is essential in mitochondrial function which is also used as a non-troponemal test due to its ability to act as an antigen?
Cardiolipin
2465
```
Composition of these glycolipids:
Ceramide
Cerebroside
Globoside
Ganglioside
Sulfatide
```
Ceramide: sphingosine + FA
```
Ceramide + ________
Glucose or galactose = Cerebroside
Oligosacchardide = Globoside
N-acetylneuramic acid = Ganglioside
Sulfated galactose = Sulfatide
```
2466
Hexosaminidase a ficiency leading to Ssx like cherry red macula, MR, hypotonia
Tay-Sachs disease
2467
A-galactosidase deficiency leading to 3Rs: recessive x-linked, rash, renal failure
Fabrys disease
2468
B-glucosidase deficiency leading to hepatosplenomegaly and erosion of long bones
Gauchers dissease
2469
Sphingomyelinase deficiency leading to hepatosplenomegaly
Nieman-pick disease
2470
The set of all proteins expressed by an individual at a particular time
Proteome
2471
Aims to identify the entire complement of proteins elaborated by a cell under diverse conditions
Proteomics
2472
What amino acid is needed to form ALA in heme synthesis?
Glycine combined with succinyl CoA
2473
Which amino acid carries nitrogen from the liver?
Alanine
2474
Which amino acids are implicated in maple syrup disease
valine, lucine, isoleucine
2475
What enzyme is responsible for the buildup of phenyl lactate, phenyl acetate, and phenylpyruvate?
Phenylalanine hydroxylase
2476
What amino acid is the precursor for niacin, serotonin, and melatonin?
Serotonin
2477
What is the amino acid precursor for homocysteine?
Methionine
2478
What amino acid contributes to the fibrous structure of collagen and interrupts a-helices in globular proteins?
Proline
2479
Increase of the combination of this Amino acid is responsible for the curly hair of people?
Cysteine + cysteine = cystine
2480
Amino acids with sites for O-linked glycosylation in the Golgi apparatus?
Serine and threonine
2481
Site for n-linked glycosylation in the ER
Asparagine
2482
Amino acid deaminated by an enzyme which results in the formation of ammonia. This is the major carrier of nitrogen to the liver from peripheral tissues,
Glutaminase deaminates glutamine
2483
Amino acid used in the determination for Folic acid deficiency. What is the test called?
Histidine used in the N-forminoglutamate excretion test
| Increased amounts of FIGu in urine by Folic acid deficient individuals after histindine intake
2484
Precursor amino acid for creatinine, urea, nitric oxide
Arginine
2485
Essential amino acids that cannot be synthesized by the body and must come from the diet
PVT TIM HALL always ARGues and never TYRes
Phenylalanine, valine, tryptophan, threonine' isoleucine, methionine, histidine, argenine, Leucine, Lysine
2486
Heme is a complex of?
Protoporphorin IX and heme
2487
What is the Bohr effect?
HBO2 + H+ HbH + O2
2488
What is an oxidized for of HB (Fe 3+) that does not bind O2 readily which could lead to chocolate cyanosis ? It is treated with oral methylene blue or ascorbic acid up to IV methylene blue.
Methemoglobin
2489
Hemoglobin bound to carbon monoxide instead of O2 leading to a cherry pink color.
Carboxyhemoglobin
2490
HB bound to carbon dioxide is called
Carbaminohenoglobin
2491
Classification of alpha and beta thalassemia
Alpha: silent carrier, a-thalassemia trait, Hb H disease, hydrops fetalis
Beta: B-thalassemia minor and major
2492
Most frequently affected collagen in Ehler Danlos syndrome leading to hyper extensible skin, tendency to bleed, hyper mobile joints, and increased risk for berry aneurysms.
Collagen type 3
2493
Collagen I mutation leading to bendable and easily fractured bones. Accompanied with blue sclerae, hearing loss, and dental imperfections.
Osteogenesis imperfecta
2494
Vitamin C deficiency leading to decreased hydroxylation of collagen. This leads to sore spongy gums, loose teeth, poor wound healing, and petecchiae on skin and mucous membranes.
Scurvy
2495
Type IV collagen defect leading to hematuria and ESRD
Alpert syndrome
2496
Collagen defect leading to kinky hair due to a deficiency of copper required by lysyl oxidase to strengthen collagen fibers.
Menke syndrome
2497
Skin breaking and blisters as a result for minor trauma. This disease is due to a defect in collage VII.
Epidermolysis bullosa
2498
Like collagen elastin has pro line and Lysine but has little and no?
Hydroxyproline
| Hydroxylysine
2499
Protein degradation mechanisms of nitrogen
Energy dependent ubiquitin-proteosome mechanism
| Non-energy dependent degradation enzyme
2500
Phases in amino acid catabolism
First phase: removal of a-amino group forming ammonia and a corresponding ketoacid
Second phase: carbon skeletons of a-ketoacids are converted to common intermediates of energy producing metabolic pathwas
2501
Two main steps in nitrogen removal from AA
1. Transamination
| 2. Oxidative deamination
2502
Where does transamination occur?
All cells of the body
2503
All but two amino acids transfer their amino groups to a-ketoglutarate except?
Lysine and threonine
2504
What is the coenzyme for the two aminotransferases?
Pyridoxal phosphate (vitamin B6)
2505
Oxidative deamination occurs where and for which amino acid only?
Liver and kidney
| Only glutamate
2506
Glutamate is oxidized by glutamate dehydrogenases and deaminated to form ?
free ammonia which is used to make urea
2507
What does the conversion of glutamate to a-ketoglutarate yield? What about vice versa?
Glutamate -> a ketoglutarate NH3 + NADH
| A ketoglutarate -> glutamate NADP+ + NH3
2508
How is excess nitrogen removal from peripheral tissues removed?
1. Glutamine: via glutamate + ammonia (through Flutamide synthaetase)
2. Alanine: via glucose -> pyruvate + glutamate -> alanine cycle
2509
Glutaminase deaminates glutamine to produce ammonium ion which is excreted from the body. Where are the two tissues this enzyme could be located?
Kidneys and small intestines
2510
Another name for urea cycle
Ornithine cycle or krebs-henseleit cycle
2511
What are the donors of the urea molecule?
1. NH3 from free ammonia
2. NH3 from aspartate
3. 1C and 1O from CO2
2512
Reactions in the urea cycle
1. Formation of carbamoyl phosphate (via carbamoyl phosphate synthetase I)
2. Formation of citrulline (via Ornithine transcarbamoylase)
3. Synthesis of arginosuccinate (arginosuccinate synthetase)
4. Cleavage of arginosuccinate to form arginine (Arginosuccinase)
5. Arginine cleavage to yield urea and Ornithine (arginase)
2513
Rate limiting step of urea cycle
Carbamoyl phosphate synthetase I
2514
Energy requirement of urea cycle
4 ATP
2515
Co factors of urea cycle
N-acetylglutamate
| Biotin
2516
Hereditary hyperammonemia produces symptoms such as
Hyperammonemia, elevated blood glutamine, decreased BUN
| Parents with lethargy, vomiting, hyperventilation, convulsions, cerebral edema, coma, and death
2517
Treatment for hereditary hyperammonemia
Low protein diet
| Administration of sodium benzoate or phenylpyruvate to capture and excrete excess nitrogen
2518
Ketogenic carbon skeletons of AA
Leucine
Lysine
Yields acetoacetate or acetyl-coa/ acetoacetyl-coa
2519
Ketogenic and glucogenic carbon skeletons of AA
```
WIFY
Phenylalanine
Isoleucine
Tryptophan
Tyrosine
```
Yields Ketogenic and glucose or glycogen by products
2520
This amino acid acts as a raw material in the biosynthesis of Heme, purines, creatine
Glycine
2521
This amino acid acts as a raw material in the biosynthesis of phospholipid, sphingolipid, purines, thymine
Serine
2522
This amino acid acts as a raw material in the biosynthesis of GABA
Glutamate
2523
This amino acid acts as a raw material in the biosynthesis of creatine, polyamines, nitric oxide
Arginine
2524
This amino acid acts as a raw material in the biosynthesis of serotonin, NAD+, NADP+, melatonin
Tryptophan
2525
This amino acid acts as a raw material in the biosynthesis of catecholamines, thyroid hormones, melanin
Tyrosine
2526
3 hormones dependent on tyrosine
Thyroid hormones
Melanin
Catecholamines
2527
Deficiency of homogenistic acid oxidase in the degrative pathway of tyrosine which results in urine turning to black on standing with dark connective tissues (ochronosis)
Alkaptonuria
2528
Congenital deficiency due tyrosinase deficieny or defective tyrosine transporters which leads to an increased risk for skin cancer.
Albinism
2529
Autosomal recessive disorder that may either be due to decreased methionine, increased cysteine, B6, and folate or decreased affinity for cystathione synthase. This results in mental retardation, osteoporosis, tall stature, lens subluxation, and atherosclerosis.
Homocystinuria
2530
Common inherited defect of renal tubular amino acid transporter for its parent compound, Ornithine, Lysine, and arginine, in the PCT of the kidneys. It eventually precipitates and cause staghorn caliculi. What is its treatment?
Cystinuria is treated with acetazolamide to alkalinize the urine
2531
The initial and last three steps of heme synthesis occurs in?
The mitochondria
2532
Heme synthesis summary
1. Formation of ALA (via ALA synthase and B6)
2. Formation of porphobilinogen
3. Formation of uroporphyrinogen
4. Formation of heme
2533
Lead inhibits what two steps in heme synthesis?
1. Introduction of Fe 2+ into protoporphyrin IX via ferrochelatase
2. Condensation of two ALA molecules by zinc containing ALA dehydratase
2534
Where is B6 a cofactors of?
1. Heme synthesis
2. Synthesis of cystathionine from homocysteine
3. Transamination between alanine and a-ketoglutarate
2535
Most common porphyria
Porphyria cutanea tarda
2536
Which part of heme synthesis do these symptoms appear?
1. Photosensitivity
2. Neuropsychiatric symptoms
1. After ring formation
| 2. Before ring formation
2537
Pyridoxine ficiency associated with isoniazid therapy results in this histopathologic finding
Sideroblastic anemia with ringed sideroblast
2538
Poisoning due to this heavy metal leads to coar basophilic stippling of RBC, peripheral neuropathy, lines in gums, increas in urinary ALA and free erythrocytes porphorin
lead poisoning
2539
Microcytic hypo chromic anemia is found in
IDA
Thalassemia
Lead poisoning
2540
Megaloblastic anemia is found in
Folate or B12 deficiency
| Pernicious anemia
2541
Normoyctic normochromic anemia is found in
Anemia of chronic kidney disease
| Blood loss
2542
Increase in MCHC is found in
Hereditary spherocytosis
2543
Summary of heme degradation
1. Formation of bilirubin
2. Uptake of bilirubin by the liver
3. Formation of bilirubin diglucoronide
4. Secretion of bilirubin into bile
5. Formation of urobilins in the intestine
2544
Colors of biliverdin, bilirubin, urobilinogen, stercolin, urobilin
```
Biliverdin: green
Bilirubin: red orange
Urobilinogen: colorless
Stercolin: brown orange red
Urobilin: yellow
```
2545
Examples of unconjugated hyperbilirubinemia
```
Hemolytic anemia
Physiologic jaundice
Crigler-najjar syndrome types I and II
Gilbert syndrome
Toxic hyperbilirubinemia
```
2546
Examples of conjugated hyperbilirubinemia
Biliary tree obstruction
Dubin-Johnson syndrome
Rotor syndrome
2547
What reaction measures total and direct bilirubin?
Van den bergs reaction
2548
What enzyme activates fatty acid for metabolism use?
Fatty-acyl-CoA synthetase
2549
Cofactor required for fatty acid activation
Vitamin B5 or Panthotenic acid
2550
Energy required to activate fatty acid
2 ATP
2551
What is the product formed in fatty acid synthesis?
Palmitate (16:0)
2552
Where does fatty acid synthesis occur?
Cytosol
Major: Liver and lactating mammary glands
Minor: adipose tissue
2553
Substrates for fatty acid synthesis
1 acetyl CoA
7 malonyl CoA
NADPH
ATP
2554
Rate limiting step in fatty acid synthesis
Acetyl CoA + ATP -> malonyl CoA
| Enzyme: acetyl CoA carboxylase
2555
Steps in fatty acid synthesis
1. Synthesis of cytoplasmic acetyl CoA (transfer of mitochondrial acetyl CoA to cytoplasm via citrate shuttle)
2. Acetyl CoA carboxylation to malonyl CoA (via acetyl CoA carboxylase with biotin) [+ insulin, citrate]
3. Assembly of palmitate (via fatty acid synthase and Vit B5)
2556
Steps in palmitate assembly
1. Condensation
2. Reduction
3. Dehydration
4. Reduction
2557
What is the fate of Palmitate after its production?
1. Further elongation in SER and mitochondria
| 2. Desaturated in the ER (but not past the 9th carbon)
2558
Main storage form of fatty acids
Triacylglycerols
2559
Where does TAG synthesis occur?
Liver and adipose tissue
2560
Sources of glycerol-3-phosphate
1. DHAP from glycolysis (liver and adipose)
| 2. Phosphorylation of free glycerol (liver)
2561
What enzyme is responsible for the release of free fatty acids from TAGs?
Hormone sensitive lipases
2562
In the bloodstream fatty acids are always bound to?
Albumin
2563
Hormone sensitive lipases can only release what free fatty acids stored in TAG?
C1 & 3 thus resulting in
TAG -> 2 free FA and 2-mono acyl glycerol
2564
Where does B-oxidation of fatty acids occur
Mitochondria of all cells, but the fatty acid activation raft occurs in the Cytosol
Exception: RBC, kidney medulla, neurons, testes
2565
Rate limiting step in B-oxidation
Fatty acyl CoA + carnitine -> fatty acyl carnitine + CoA
| Enzyme: carnitine acyl transferase I
2566
Cutoff number of carbons that do not need a shuttle
Less than 12 carbons
2567
Steps in the carnitine shuttle
1. Fatty acyl synthase activates the fatty acid
2. Carnitine acyl transferase 1 attaches to fatty acyl to carnitine in the outer mitochondrial membrane
3. Fatty acyl-carnitine is shuttle through the inner membrane
4. Carnitine acyl transferase-2 transfers fatty acyl group back to a CoA in the mitochondrial matrix
2568
Steps in beta oxidation
1. Oxidation
2. Hydratiion
3. Oxidation
4. Thiolysis
2569
Beta oxidation of fatty acids with an odd number of carbon atoms releases?
Propionyl CoA which is converted to methylmalonyl coa (requires B12) then to succinyl CoA
2570
Which is responsible for the conversion of very long chain fatty acids?
Peroxisomes but if unsaturated it requires 3,2 enol-CoA isomerase
2571
Energy yield in ATP of beta oxidation of palmitate
129 ATP
7 NADH= 21
7 FAD= 14
8 acetyl CoA= 96
Activation = -2
2572
Intake of this compound depletes the body's NAD+ supply leading to accumulation Of fat in the liver
Alcohol
2573
Type of carnitine deficiency which leads to impaired FA oxidation and ketogenesis with hypoglycemia?
CPT-1 deficiency
2574
Type of carnitine deficiency which affects skeletal muscle and when severe the liver
CPT-2 deficiency
2575
It is a disorder school results in decreased fatty acid oxidation. Without the ATP to support gluconeogenesis, hypoglycemia becomes profound which may eventually leads to SIDS. It is prevented by frequent feeding with high carbohydrate and low fat diet.
Medium-chain fatty acyl-CoA dehydrogenase (MCAD) deficiency
2576
Associated with eating unripe fruit of the akee tree which contains hypoglycin thus activating MC and SC acyl CoA dehydrogenase
Jamaican vomiting sickness
2577
Rare neurological disorder which results to the accumulation of phytanic acid found in plant food stuff which blocks Boxidation
Refsum disease
2578
Cerebrohepatorenal syndrome resulting from the absence of peroxisomes in all tissues, it is characterized by liver dysfunction, jaundice, MR, weakness, hypotonia, and craniofacial dimorphism
Zellweger syndrome
2579
Defect in peroxismal activation of VLCFA thus leading to its accumulation. Ssx: apathy, behavral change, then visual loss spasticity, ataxia. All due to the fact since VLCFA are found in myelin tissue.
X-lied adrenoleukodystrophy
2580
Where does ketogenesis occur?
Liver mitochondria
2581
Products of ketogenesis
Acetoacetate and B-hydroxybutyrate (fuel)
| Acetone (cannot be used as fuel)
2582
Rate limiting step of ketogenesis
Acetoacetyl CoA + acetyl CoA --(HMG CoA synthase)--> HMG CoA
2583
What are the initial products that lead to the formation of acetyl CoA in ketogenolysis?
B-hydroxybutyrate -> acetoacetate -> acetyl coa
2584
What peripheral tissues can oxidize ketone bodes?
Those with mitochondria like the renal cortex, brain, and skeletal muscle
2585
Why cant liver convert acetoacetate to acetyl CoA?
It lacks succinyl-CoA acetoacetyl-CoA reductase (thiophorase)
2586
What is the Urine test for ketones? What ketone type does not it detect?
Nitroprusside test
Does not detect b-hydroxybutyrate
2587
Which part of cholesterol can a fatty acid attach to form a cholesteryl ester?
Single hydroxyl group of carbon 3 of the alpha ring
2588
Where does cholesterol synthesis occur?
All cells in the Cytosol and SER majority of which are found in the liver and intestines
2589
Substrates of cholesterol synthesis
Acetyl CoA, NADPH, ATP
2590
Rate limiting step in cholesterol synthesis
HMG CoA --(HMG CoA reductase)--> mevalonate
2591
Steps in Cholestid synthesis
1. Biosynthesis of mevalonate
2. Formation of isoprenoid units
3. Isoprene unit is formed from 6 isoprenoid units
4. Formation of lanosterol
5. Formation of cholesterol
2592
How is the cholesterol ring eliminated?
Through conversion to bile salts then secretion to bile
2593
Bile acid synthesis, found in the liver and Cytosol, rate limiting enzyme is?
Cholesterol-7-a-hydroxylase
2594
What are the primary bile acids?
Cholic acid
| Chenocholic acid
2595
What are the two amino acids used in bile acid conjugation to form bile salts?
Taurine and glycine
2596
What are the secondary bile acids?
Deoxycholic acid
| Lithocholic acid
2597
Where does steroid hormone synthesis occur?
SER of the adrenal glands, ovaries and testes, and placenta
2598
What is blocked by the drug aminogluthetimide?
The conversion of cholesterol to pregnenolone by desmolase
2599
The enzyme responsible for the breakdown of TAG to FA and:
A) 2-MAG from diet
B) FREE glycerol from chylomicrons and VLDL
C) 2-MAG from adipose
A) pancreatic lipase
B) Lipoprotein lipase
C) hormone sensitive lipase
2600
Lipoprotein with the largest percentage of TG
Chylomicrons
2601
Lipoprotein with the largest percentage of cholesteryl esters
LDL
2602
Chylomicrons transport TG and cholesterol from where to where?
Intestines to tissues
2603
VLDL transports TG from where to where?
Liver to tissues
2604
What apoprotein activates lipoprotein lipase?
APO-CII
2605
What apolipoprotein uptakes remnants by the liver?
APO E
2606
Apolipoprotein B-48 is used by chylomicrons which are created by the?
Epithelial cells
2607
What apolipoprotein is secreted by the liver for VDL?
B-100
2608
How does IDL become LDL?
By picking up cholesterol from HD!
2609
Which apoprotein delivers cholesterol into cells?
LDL
2610
Which apolipoprotein is used by HDL to activate lecithin cholesterol acyl transferase or LCAT to produce cholesterol esters?
APO-A1
2611
Difference between Type II familial hypercholesterolemia and type IV familial hypertriglyceredemia?
The former has high LDL leader to xanthomas and xanthelasmas with increased risk of atherosclerosis and CHD
The latter has increased VLDL production leading to a triad of
1. DM type 2
2. CAD
3. Obesity
2612
Phospholipid is composed of
DAG
Alcohol
Phosphodiester bond
2613
Most abundant phospholipid which is important in nervous transmission
Phosphatidylcholine
2614
Phospholipid playing a role in apoptosis
Phosphatidyl serine
2615
Phospholipid that is a major component of surfactant?
Dipalmitoylphosphatidylcholine
2616
Phospholipid reservoir for arachidonic acid in the membranes
Phosphatidylinositol
2617
What phospholipid is essential in mitochondrial function which is also used as a non-troponemal test due to its ability to act as an antigen?
Cardiolipin
2618
```
Composition of these glycolipids:
Ceramide
Cerebroside
Globoside
Ganglioside
Sulfatide
```
Ceramide: sphingosine + FA
```
Ceramide + ________
Glucose or galactose = Cerebroside
Oligosacchardide = Globoside
N-acetylneuramic acid = Ganglioside
Sulfated galactose = Sulfatide
```
2619
Hexosaminidase a ficiency leading to Ssx like cherry red macula, MR, hypotonia
Tay-Sachs disease
2620
A-galactosidase deficiency leading to 3Rs: recessive x-linked, rash, renal failure
Fabrys disease
2621
B-glucosidase deficiency leading to hepatosplenomegaly and erosion of long bones
Gauchers dissease
2622
Sphingomyelinase deficiency leading to hepatosplenomegaly
Nieman-pick disease
2623
The set of all proteins expressed by an individual at a particular time
Proteome
2624
Aims to identify the entire complement of proteins elaborated by a cell under diverse conditions
Proteomics
2625
What amino acid is needed to form ALA in heme synthesis?
Glycine combined with succinyl CoA
2626
Which amino acid carries nitrogen from the liver?
Alanine
2627
Which amino acids are implicated in maple syrup disease
valine, lucine, isoleucine
2628
What enzyme is responsible for the buildup of phenyl lactate, phenyl acetate, and phenylpyruvate?
Phenylalanine hydroxylase
2629
What amino acid is the precursor for niacin, serotonin, and melatonin?
Serotonin
2630
What is the amino acid precursor for homocysteine?
Methionine
2631
What amino acid contributes to the fibrous structure of collagen and interrupts a-helices in globular proteins?
Proline
2632
Increase of the combination of this Amino acid is responsible for the curly hair of people?
Cysteine + cysteine = cystine
2633
Amino acids with sites for O-linked glycosylation in the Golgi apparatus?
Serine and threonine
2634
Site for n-linked glycosylation in the ER
Asparagine
2635
Amino acid deaminated by an enzyme which results in the formation of ammonia. This is the major carrier of nitrogen to the liver from peripheral tissues,
Glutaminase deaminates glutamine
2636
Amino acid used in the determination for Folic acid deficiency. What is the test called?
Histidine used in the N-forminoglutamate excretion test
| Increased amounts of FIGu in urine by Folic acid deficient individuals after histindine intake
2637
Precursor amino acid for creatinine, urea, nitric oxide
Arginine
2638
Essential amino acids that cannot be synthesized by the body and must come from the diet
PVT TIM HALL always ARGues and never TYRes
Phenylalanine, valine, tryptophan, threonine' isoleucine, methionine, histidine, argenine, Leucine, Lysine
2639
Heme is a complex of?
Protoporphorin IX and heme
2640
What is the Bohr effect?
HBO2 + H+ HbH + O2
2641
What is an oxidized for of HB (Fe 3+) that does not bind O2 readily which could lead to chocolate cyanosis ? It is treated with oral methylene blue or ascorbic acid up to IV methylene blue.
Methemoglobin
2642
Hemoglobin bound to carbon monoxide instead of O2 leading to a cherry pink color.
Carboxyhemoglobin
2643
HB bound to carbon dioxide is called
Carbaminohenoglobin
2644
Classification of alpha and beta thalassemia
Alpha: silent carrier, a-thalassemia trait, Hb H disease, hydrops fetalis
Beta: B-thalassemia minor and major
2645
Most frequently affected collagen in Ehler Danlos syndrome leading to hyper extensible skin, tendency to bleed, hyper mobile joints, and increased risk for berry aneurysms.
Collagen type 3
2646
Collagen I mutation leading to bendable and easily fractured bones. Accompanied with blue sclerae, hearing loss, and dental imperfections.
Osteogenesis imperfecta
2647
Vitamin C deficiency leading to decreased hydroxylation of collagen. This leads to sore spongy gums, loose teeth, poor wound healing, and petecchiae on skin and mucous membranes.
Scurvy
2648
Type IV collagen defect leading to hematuria and ESRD
Alpert syndrome
2649
Collagen defect leading to kinky hair due to a deficiency of copper required by lysyl oxidase to strengthen collagen fibers.
Menke syndrome
2650
Skin breaking and blisters as a result for minor trauma. This disease is due to a defect in collage VII.
Epidermolysis bullosa
2651
Like collagen elastin has pro line and Lysine but has little and no?
Hydroxyproline
| Hydroxylysine
2652
Protein degradation mechanisms of nitrogen
Energy dependent ubiquitin-proteosome mechanism
| Non-energy dependent degradation enzyme
2653
Phases in amino acid catabolism
First phase: removal of a-amino group forming ammonia and a corresponding ketoacid
Second phase: carbon skeletons of a-ketoacids are converted to common intermediates of energy producing metabolic pathwas
2654
Two main steps in nitrogen removal from AA
1. Transamination
| 2. Oxidative deamination
2655
Where does transamination occur?
All cells of the body
2656
All but two amino acids transfer their amino groups to a-ketoglutarate except?
Lysine and threonine
2657
What is the coenzyme for the two aminotransferases?
Pyridoxal phosphate (vitamin B6)
2658
Oxidative deamination occurs where and for which amino acid only?
Liver and kidney
| Only glutamate
2659
Glutamate is oxidized by glutamate dehydrogenases and deaminated to form ?
free ammonia which is used to make urea
2660
What does the conversion of glutamate to a-ketoglutarate yield? What about vice versa?
Glutamate -> a ketoglutarate NH3 + NADH
| A ketoglutarate -> glutamate NADP+ + NH3
2661
How is excess nitrogen removal from peripheral tissues removed?
1. Glutamine: via glutamate + ammonia (through Flutamide synthaetase)
2. Alanine: via glucose -> pyruvate + glutamate -> alanine cycle
2662
Glutaminase deaminates glutamine to produce ammonium ion which is excreted from the body. Where are the two tissues this enzyme could be located?
Kidneys and small intestines
2663
Another name for urea cycle
Ornithine cycle or krebs-henseleit cycle
2664
What are the donors of the urea molecule?
1. NH3 from free ammonia
2. NH3 from aspartate
3. 1C and 1O from CO2
2665
Reactions in the urea cycle
1. Formation of carbamoyl phosphate (via carbamoyl phosphate synthetase I)
2. Formation of citrulline (via Ornithine transcarbamoylase)
3. Synthesis of arginosuccinate (arginosuccinate synthetase)
4. Cleavage of arginosuccinate to form arginine (Arginosuccinase)
5. Arginine cleavage to yield urea and Ornithine (arginase)
2666
Rate limiting step of urea cycle
Carbamoyl phosphate synthetase I
2667
Energy requirement of urea cycle
4 ATP
2668
Co factors of urea cycle
N-acetylglutamate
| Biotin
2669
Hereditary hyperammonemia produces symptoms such as
Hyperammonemia, elevated blood glutamine, decreased BUN
| Parents with lethargy, vomiting, hyperventilation, convulsions, cerebral edema, coma, and death
2670
Treatment for hereditary hyperammonemia
Low protein diet
| Administration of sodium benzoate or phenylpyruvate to capture and excrete excess nitrogen
2671
Ketogenic carbon skeletons of AA
Leucine
Lysine
Yields acetoacetate or acetyl-coa/ acetoacetyl-coa
2672
Ketogenic and glucogenic carbon skeletons of AA
```
WIFY
Phenylalanine
Isoleucine
Tryptophan
Tyrosine
```
Yields Ketogenic and glucose or glycogen by products
2673
This amino acid acts as a raw material in the biosynthesis of Heme, purines, creatine
Glycine
2674
This amino acid acts as a raw material in the biosynthesis of phospholipid, sphingolipid, purines, thymine
Serine
2675
This amino acid acts as a raw material in the biosynthesis of GABA
Glutamate
2676
This amino acid acts as a raw material in the biosynthesis of creatine, polyamines, nitric oxide
Arginine
2677
This amino acid acts as a raw material in the biosynthesis of serotonin, NAD+, NADP+, melatonin
Tryptophan
2678
This amino acid acts as a raw material in the biosynthesis of catecholamines, thyroid hormones, melanin
Tyrosine
2679
3 hormones dependent on tyrosine
Thyroid hormones
Melanin
Catecholamines
2680
Deficiency of homogenistic acid oxidase in the degrative pathway of tyrosine which results in urine turning to black on standing with dark connective tissues (ochronosis)
Alkaptonuria
2681
Congenital deficiency due tyrosinase deficieny or defective tyrosine transporters which leads to an increased risk for skin cancer.
Albinism
2682
Autosomal recessive disorder that may either be due to decreased methionine, increased cysteine, B6, and folate or decreased affinity for cystathione synthase. This results in mental retardation, osteoporosis, tall stature, lens subluxation, and atherosclerosis.
Homocystinuria
2683
Common inherited defect of renal tubular amino acid transporter for its parent compound, Ornithine, Lysine, and arginine, in the PCT of the kidneys. It eventually precipitates and cause staghorn caliculi. What is its treatment?
Cystinuria is treated with acetazolamide to alkalinize the urine
2684
The initial and last three steps of heme synthesis occurs in?
The mitochondria
2685
Heme synthesis summary
1. Formation of ALA (via ALA synthase and B6)
2. Formation of porphobilinogen
3. Formation of uroporphyrinogen
4. Formation of heme
2686
Lead inhibits what two steps in heme synthesis?
1. Introduction of Fe 2+ into protoporphyrin IX via ferrochelatase
2. Condensation of two ALA molecules by zinc containing ALA dehydratase
2687
Where is B6 a cofactors of?
1. Heme synthesis
2. Synthesis of cystathionine from homocysteine
3. Transamination between alanine and a-ketoglutarate
2688
Most common porphyria
Porphyria cutanea tarda
2689
Which part of heme synthesis do these symptoms appear?
1. Photosensitivity
2. Neuropsychiatric symptoms
1. After ring formation
| 2. Before ring formation
2690
Pyridoxine ficiency associated with isoniazid therapy results in this histopathologic finding
Sideroblastic anemia with ringed sideroblast
2691
Poisoning due to this heavy metal leads to coar basophilic stippling of RBC, peripheral neuropathy, lines in gums, increas in urinary ALA and free erythrocytes porphorin
lead poisoning
2692
Microcytic hypo chromic anemia is found in
IDA
Thalassemia
Lead poisoning
2693
Megaloblastic anemia is found in
Folate or B12 deficiency
| Pernicious anemia
2694
Normoyctic normochromic anemia is found in
Anemia of chronic kidney disease
| Blood loss
2695
Increase in MCHC is found in
Hereditary spherocytosis
2696
Summary of heme degradation
1. Formation of bilirubin
2. Uptake of bilirubin by the liver
3. Formation of bilirubin diglucoronide
4. Secretion of bilirubin into bile
5. Formation of urobilins in the intestine
2697
Colors of biliverdin, bilirubin, urobilinogen, stercolin, urobilin
```
Biliverdin: green
Bilirubin: red orange
Urobilinogen: colorless
Stercolin: brown orange red
Urobilin: yellow
```
2698
Examples of unconjugated hyperbilirubinemia
```
Hemolytic anemia
Physiologic jaundice
Crigler-najjar syndrome types I and II
Gilbert syndrome
Toxic hyperbilirubinemia
```
2699
Examples of conjugated hyperbilirubinemia
Biliary tree obstruction
Dubin-Johnson syndrome
Rotor syndrome
2700
What reaction measures total and direct bilirubin?
Van den bergs reaction
2701
What enzyme activates fatty acid for metabolism use?
Fatty-acyl-CoA synthetase
2702
Cofactor required for fatty acid activation
Vitamin B5 or Panthotenic acid
2703
Energy required to activate fatty acid
2 ATP
2704
What is the product formed in fatty acid synthesis?
Palmitate (16:0)
2705
Where does fatty acid synthesis occur?
Cytosol
Major: Liver and lactating mammary glands
Minor: adipose tissue
2706
Substrates for fatty acid synthesis
1 acetyl CoA
7 malonyl CoA
NADPH
ATP
2707
Rate limiting step in fatty acid synthesis
Acetyl CoA + ATP -> malonyl CoA
| Enzyme: acetyl CoA carboxylase
2708
Steps in fatty acid synthesis
1. Synthesis of cytoplasmic acetyl CoA (transfer of mitochondrial acetyl CoA to cytoplasm via citrate shuttle)
2. Acetyl CoA carboxylation to malonyl CoA (via acetyl CoA carboxylase with biotin) [+ insulin, citrate]
3. Assembly of palmitate (via fatty acid synthase and Vit B5)
2709
Steps in palmitate assembly
1. Condensation
2. Reduction
3. Dehydration
4. Reduction
2710
What is the fate of Palmitate after its production?
1. Further elongation in SER and mitochondria
| 2. Desaturated in the ER (but not past the 9th carbon)
2711
Main storage form of fatty acids
Triacylglycerols
2712
Where does TAG synthesis occur?
Liver and adipose tissue
2713
Sources of glycerol-3-phosphate
1. DHAP from glycolysis (liver and adipose)
| 2. Phosphorylation of free glycerol (liver)
2714
What enzyme is responsible for the release of free fatty acids from TAGs?
Hormone sensitive lipases
2715
In the bloodstream fatty acids are always bound to?
Albumin
2716
Hormone sensitive lipases can only release what free fatty acids stored in TAG?
C1 & 3 thus resulting in
TAG -> 2 free FA and 2-mono acyl glycerol
2717
Where does B-oxidation of fatty acids occur
Mitochondria of all cells, but the fatty acid activation raft occurs in the Cytosol
Exception: RBC, kidney medulla, neurons, testes
2718
Rate limiting step in B-oxidation
Fatty acyl CoA + carnitine -> fatty acyl carnitine + CoA
| Enzyme: carnitine acyl transferase I
2719
Cutoff number of carbons that do not need a shuttle
Less than 12 carbons
2720
Steps in the carnitine shuttle
1. Fatty acyl synthase activates the fatty acid
2. Carnitine acyl transferase 1 attaches to fatty acyl to carnitine in the outer mitochondrial membrane
3. Fatty acyl-carnitine is shuttle through the inner membrane
4. Carnitine acyl transferase-2 transfers fatty acyl group back to a CoA in the mitochondrial matrix
2721
Steps in beta oxidation
1. Oxidation
2. Hydratiion
3. Oxidation
4. Thiolysis
2722
Beta oxidation of fatty acids with an odd number of carbon atoms releases?
Propionyl CoA which is converted to methylmalonyl coa (requires B12) then to succinyl CoA
2723
Which is responsible for the conversion of very long chain fatty acids?
Peroxisomes but if unsaturated it requires 3,2 enol-CoA isomerase
2724
Energy yield in ATP of beta oxidation of palmitate
129 ATP
7 NADH= 21
7 FAD= 14
8 acetyl CoA= 96
Activation = -2
2725
Intake of this compound depletes the body's NAD+ supply leading to accumulation Of fat in the liver
Alcohol
2726
Type of carnitine deficiency which leads to impaired FA oxidation and ketogenesis with hypoglycemia?
CPT-1 deficiency
2727
Type of carnitine deficiency which affects skeletal muscle and when severe the liver
CPT-2 deficiency
2728
It is a disorder school results in decreased fatty acid oxidation. Without the ATP to support gluconeogenesis, hypoglycemia becomes profound which may eventually leads to SIDS. It is prevented by frequent feeding with high carbohydrate and low fat diet.
Medium-chain fatty acyl-CoA dehydrogenase (MCAD) deficiency
2729
Associated with eating unripe fruit of the akee tree which contains hypoglycin thus activating MC and SC acyl CoA dehydrogenase
Jamaican vomiting sickness
2730
Rare neurological disorder which results to the accumulation of phytanic acid found in plant food stuff which blocks Boxidation
Refsum disease
2731
Cerebrohepatorenal syndrome resulting from the absence of peroxisomes in all tissues, it is characterized by liver dysfunction, jaundice, MR, weakness, hypotonia, and craniofacial dimorphism
Zellweger syndrome
2732
Defect in peroxismal activation of VLCFA thus leading to its accumulation. Ssx: apathy, behavral change, then visual loss spasticity, ataxia. All due to the fact since VLCFA are found in myelin tissue.
X-lied adrenoleukodystrophy
2733
Where does ketogenesis occur?
Liver mitochondria
2734
Products of ketogenesis
Acetoacetate and B-hydroxybutyrate (fuel)
| Acetone (cannot be used as fuel)
2735
Rate limiting step of ketogenesis
Acetoacetyl CoA + acetyl CoA --(HMG CoA synthase)--> HMG CoA
2736
What are the initial products that lead to the formation of acetyl CoA in ketogenolysis?
B-hydroxybutyrate -> acetoacetate -> acetyl coa
2737
What peripheral tissues can oxidize ketone bodes?
Those with mitochondria like the renal cortex, brain, and skeletal muscle
2738
Why cant liver convert acetoacetate to acetyl CoA?
It lacks succinyl-CoA acetoacetyl-CoA reductase (thiophorase)
2739
What is the Urine test for ketones? What ketone type does not it detect?
Nitroprusside test
Does not detect b-hydroxybutyrate
2740
Which part of cholesterol can a fatty acid attach to form a cholesteryl ester?
Single hydroxyl group of carbon 3 of the alpha ring
2741
Where does cholesterol synthesis occur?
All cells in the Cytosol and SER majority of which are found in the liver and intestines
2742
Substrates of cholesterol synthesis
Acetyl CoA, NADPH, ATP
2743
Rate limiting step in cholesterol synthesis
HMG CoA --(HMG CoA reductase)--> mevalonate
2744
Steps in Cholestid synthesis
1. Biosynthesis of mevalonate
2. Formation of isoprenoid units
3. Isoprene unit is formed from 6 isoprenoid units
4. Formation of lanosterol
5. Formation of cholesterol
2745
How is the cholesterol ring eliminated?
Through conversion to bile salts then secretion to bile
2746
Bile acid synthesis, found in the liver and Cytosol, rate limiting enzyme is?
Cholesterol-7-a-hydroxylase
2747
What are the primary bile acids?
Cholic acid
| Chenocholic acid
2748
What are the two amino acids used in bile acid conjugation to form bile salts?
Taurine and glycine
2749
What are the secondary bile acids?
Deoxycholic acid
| Lithocholic acid
2750
Where does steroid hormone synthesis occur?
SER of the adrenal glands, ovaries and testes, and placenta
2751
What is blocked by the drug aminogluthetimide?
The conversion of cholesterol to pregnenolone by desmolase
2752
The enzyme responsible for the breakdown of TAG to FA and:
A) 2-MAG from diet
B) FREE glycerol from chylomicrons and VLDL
C) 2-MAG from adipose
A) pancreatic lipase
B) Lipoprotein lipase
C) hormone sensitive lipase
2753
Lipoprotein with the largest percentage of TG
Chylomicrons
2754
Lipoprotein with the largest percentage of cholesteryl esters
LDL
2755
Chylomicrons transport TG and cholesterol from where to where?
Intestines to tissues
2756
VLDL transports TG from where to where?
Liver to tissues
2757
What apoprotein activates lipoprotein lipase?
APO-CII
2758
What apolipoprotein uptakes remnants by the liver?
APO E
2759
Apolipoprotein B-48 is used by chylomicrons which are created by the?
Epithelial cells
2760
What apolipoprotein is secreted by the liver for VDL?
B-100
2761
How does IDL become LDL?
By picking up cholesterol from HD!
2762
Which apoprotein delivers cholesterol into cells?
LDL
2763
Which apolipoprotein is used by HDL to activate lecithin cholesterol acyl transferase or LCAT to produce cholesterol esters?
APO-A1
2764
Difference between Type II familial hypercholesterolemia and type IV familial hypertriglyceredemia?
The former has high LDL leader to xanthomas and xanthelasmas with increased risk of atherosclerosis and CHD
The latter has increased VLDL production leading to a triad of
1. DM type 2
2. CAD
3. Obesity
2765
Phospholipid is composed of
DAG
Alcohol
Phosphodiester bond
2766
Most abundant phospholipid which is important in nervous transmission
Phosphatidylcholine
2767
Phospholipid playing a role in apoptosis
Phosphatidyl serine
2768
Phospholipid that is a major component of surfactant?
Dipalmitoylphosphatidylcholine
2769
Phospholipid reservoir for arachidonic acid in the membranes
Phosphatidylinositol
2770
What phospholipid is essential in mitochondrial function which is also used as a non-troponemal test due to its ability to act as an antigen?
Cardiolipin
2771
```
Composition of these glycolipids:
Ceramide
Cerebroside
Globoside
Ganglioside
Sulfatide
```
Ceramide: sphingosine + FA
```
Ceramide + ________
Glucose or galactose = Cerebroside
Oligosacchardide = Globoside
N-acetylneuramic acid = Ganglioside
Sulfated galactose = Sulfatide
```
2772
Hexosaminidase a ficiency leading to Ssx like cherry red macula, MR, hypotonia
Tay-Sachs disease
2773
A-galactosidase deficiency leading to 3Rs: recessive x-linked, rash, renal failure
Fabrys disease
2774
B-glucosidase deficiency leading to hepatosplenomegaly and erosion of long bones
Gauchers dissease
2775
Sphingomyelinase deficiency leading to hepatosplenomegaly
Nieman-pick disease
2776
The set of all proteins expressed by an individual at a particular time
Proteome
2777
Aims to identify the entire complement of proteins elaborated by a cell under diverse conditions
Proteomics
2778
What amino acid is needed to form ALA in heme synthesis?
Glycine combined with succinyl CoA
2779
Which amino acid carries nitrogen from the liver?
Alanine
2780
Which amino acids are implicated in maple syrup disease
valine, lucine, isoleucine
2781
What enzyme is responsible for the buildup of phenyl lactate, phenyl acetate, and phenylpyruvate?
Phenylalanine hydroxylase
2782
What amino acid is the precursor for niacin, serotonin, and melatonin?
Serotonin
2783
What is the amino acid precursor for homocysteine?
Methionine
2784
What amino acid contributes to the fibrous structure of collagen and interrupts a-helices in globular proteins?
Proline
2785
Increase of the combination of this Amino acid is responsible for the curly hair of people?
Cysteine + cysteine = cystine
2786
Amino acids with sites for O-linked glycosylation in the Golgi apparatus?
Serine and threonine
2787
Site for n-linked glycosylation in the ER
Asparagine
2788
Amino acid deaminated by an enzyme which results in the formation of ammonia. This is the major carrier of nitrogen to the liver from peripheral tissues,
Glutaminase deaminates glutamine
2789
Amino acid used in the determination for Folic acid deficiency. What is the test called?
Histidine used in the N-forminoglutamate excretion test
| Increased amounts of FIGu in urine by Folic acid deficient individuals after histindine intake
2790
Precursor amino acid for creatinine, urea, nitric oxide
Arginine
2791
Essential amino acids that cannot be synthesized by the body and must come from the diet
PVT TIM HALL always ARGues and never TYRes
Phenylalanine, valine, tryptophan, threonine' isoleucine, methionine, histidine, argenine, Leucine, Lysine
2792
Heme is a complex of?
Protoporphorin IX and heme
2793
What is the Bohr effect?
HBO2 + H+ HbH + O2
2794
What is an oxidized for of HB (Fe 3+) that does not bind O2 readily which could lead to chocolate cyanosis ? It is treated with oral methylene blue or ascorbic acid up to IV methylene blue.
Methemoglobin
2795
Hemoglobin bound to carbon monoxide instead of O2 leading to a cherry pink color.
Carboxyhemoglobin
2796
HB bound to carbon dioxide is called
Carbaminohenoglobin
2797
Classification of alpha and beta thalassemia
Alpha: silent carrier, a-thalassemia trait, Hb H disease, hydrops fetalis
Beta: B-thalassemia minor and major
2798
Most frequently affected collagen in Ehler Danlos syndrome leading to hyper extensible skin, tendency to bleed, hyper mobile joints, and increased risk for berry aneurysms.
Collagen type 3
2799
Collagen I mutation leading to bendable and easily fractured bones. Accompanied with blue sclerae, hearing loss, and dental imperfections.
Osteogenesis imperfecta
2800
Vitamin C deficiency leading to decreased hydroxylation of collagen. This leads to sore spongy gums, loose teeth, poor wound healing, and petecchiae on skin and mucous membranes.
Scurvy
2801
Type IV collagen defect leading to hematuria and ESRD
Alpert syndrome
2802
Collagen defect leading to kinky hair due to a deficiency of copper required by lysyl oxidase to strengthen collagen fibers.
Menke syndrome
2803
Skin breaking and blisters as a result for minor trauma. This disease is due to a defect in collage VII.
Epidermolysis bullosa
2804
Like collagen elastin has pro line and Lysine but has little and no?
Hydroxyproline
| Hydroxylysine
2805
Protein degradation mechanisms of nitrogen
Energy dependent ubiquitin-proteosome mechanism
| Non-energy dependent degradation enzyme
2806
Phases in amino acid catabolism
First phase: removal of a-amino group forming ammonia and a corresponding ketoacid
Second phase: carbon skeletons of a-ketoacids are converted to common intermediates of energy producing metabolic pathwas
2807
Two main steps in nitrogen removal from AA
1. Transamination
| 2. Oxidative deamination
2808
Where does transamination occur?
All cells of the body
2809
All but two amino acids transfer their amino groups to a-ketoglutarate except?
Lysine and threonine
2810
What is the coenzyme for the two aminotransferases?
Pyridoxal phosphate (vitamin B6)
2811
Oxidative deamination occurs where and for which amino acid only?
Liver and kidney
| Only glutamate
2812
Glutamate is oxidized by glutamate dehydrogenases and deaminated to form ?
free ammonia which is used to make urea
2813
What does the conversion of glutamate to a-ketoglutarate yield? What about vice versa?
Glutamate -> a ketoglutarate NH3 + NADH
| A ketoglutarate -> glutamate NADP+ + NH3
2814
How is excess nitrogen removal from peripheral tissues removed?
1. Glutamine: via glutamate + ammonia (through Flutamide synthaetase)
2. Alanine: via glucose -> pyruvate + glutamate -> alanine cycle
2815
Glutaminase deaminates glutamine to produce ammonium ion which is excreted from the body. Where are the two tissues this enzyme could be located?
Kidneys and small intestines
2816
Another name for urea cycle
Ornithine cycle or krebs-henseleit cycle
2817
What are the donors of the urea molecule?
1. NH3 from free ammonia
2. NH3 from aspartate
3. 1C and 1O from CO2
2818
Reactions in the urea cycle
1. Formation of carbamoyl phosphate (via carbamoyl phosphate synthetase I)
2. Formation of citrulline (via Ornithine transcarbamoylase)
3. Synthesis of arginosuccinate (arginosuccinate synthetase)
4. Cleavage of arginosuccinate to form arginine (Arginosuccinase)
5. Arginine cleavage to yield urea and Ornithine (arginase)
2819
Rate limiting step of urea cycle
Carbamoyl phosphate synthetase I
2820
Energy requirement of urea cycle
4 ATP
2821
Co factors of urea cycle
N-acetylglutamate
| Biotin
2822
Hereditary hyperammonemia produces symptoms such as
Hyperammonemia, elevated blood glutamine, decreased BUN
| Parents with lethargy, vomiting, hyperventilation, convulsions, cerebral edema, coma, and death
2823
Treatment for hereditary hyperammonemia
Low protein diet
| Administration of sodium benzoate or phenylpyruvate to capture and excrete excess nitrogen
2824
Ketogenic carbon skeletons of AA
Leucine
Lysine
Yields acetoacetate or acetyl-coa/ acetoacetyl-coa
2825
Ketogenic and glucogenic carbon skeletons of AA
```
WIFY
Phenylalanine
Isoleucine
Tryptophan
Tyrosine
```
Yields Ketogenic and glucose or glycogen by products
2826
This amino acid acts as a raw material in the biosynthesis of Heme, purines, creatine
Glycine
2827
This amino acid acts as a raw material in the biosynthesis of phospholipid, sphingolipid, purines, thymine
Serine
2828
This amino acid acts as a raw material in the biosynthesis of GABA
Glutamate
2829
This amino acid acts as a raw material in the biosynthesis of creatine, polyamines, nitric oxide
Arginine
2830
This amino acid acts as a raw material in the biosynthesis of serotonin, NAD+, NADP+, melatonin
Tryptophan
2831
This amino acid acts as a raw material in the biosynthesis of catecholamines, thyroid hormones, melanin
Tyrosine
2832
3 hormones dependent on tyrosine
Thyroid hormones
Melanin
Catecholamines
2833
Deficiency of homogenistic acid oxidase in the degrative pathway of tyrosine which results in urine turning to black on standing with dark connective tissues (ochronosis)
Alkaptonuria
2834
Congenital deficiency due tyrosinase deficieny or defective tyrosine transporters which leads to an increased risk for skin cancer.
Albinism
2835
Autosomal recessive disorder that may either be due to decreased methionine, increased cysteine, B6, and folate or decreased affinity for cystathione synthase. This results in mental retardation, osteoporosis, tall stature, lens subluxation, and atherosclerosis.
Homocystinuria
2836
Common inherited defect of renal tubular amino acid transporter for its parent compound, Ornithine, Lysine, and arginine, in the PCT of the kidneys. It eventually precipitates and cause staghorn caliculi. What is its treatment?
Cystinuria is treated with acetazolamide to alkalinize the urine
2837
The initial and last three steps of heme synthesis occurs in?
The mitochondria
2838
Heme synthesis summary
1. Formation of ALA (via ALA synthase and B6)
2. Formation of porphobilinogen
3. Formation of uroporphyrinogen
4. Formation of heme
2839
Lead inhibits what two steps in heme synthesis?
1. Introduction of Fe 2+ into protoporphyrin IX via ferrochelatase
2. Condensation of two ALA molecules by zinc containing ALA dehydratase
2840
Where is B6 a cofactors of?
1. Heme synthesis
2. Synthesis of cystathionine from homocysteine
3. Transamination between alanine and a-ketoglutarate
2841
Most common porphyria
Porphyria cutanea tarda
2842
Which part of heme synthesis do these symptoms appear?
1. Photosensitivity
2. Neuropsychiatric symptoms
1. After ring formation
| 2. Before ring formation
2843
Pyridoxine ficiency associated with isoniazid therapy results in this histopathologic finding
Sideroblastic anemia with ringed sideroblast
2844
Poisoning due to this heavy metal leads to coar basophilic stippling of RBC, peripheral neuropathy, lines in gums, increas in urinary ALA and free erythrocytes porphorin
lead poisoning
2845
Microcytic hypo chromic anemia is found in
IDA
Thalassemia
Lead poisoning
2846
Megaloblastic anemia is found in
Folate or B12 deficiency
| Pernicious anemia
2847
Normoyctic normochromic anemia is found in
Anemia of chronic kidney disease
| Blood loss
2848
Increase in MCHC is found in
Hereditary spherocytosis
2849
Summary of heme degradation
1. Formation of bilirubin
2. Uptake of bilirubin by the liver
3. Formation of bilirubin diglucoronide
4. Secretion of bilirubin into bile
5. Formation of urobilins in the intestine
2850
Colors of biliverdin, bilirubin, urobilinogen, stercolin, urobilin
```
Biliverdin: green
Bilirubin: red orange
Urobilinogen: colorless
Stercolin: brown orange red
Urobilin: yellow
```
2851
Examples of unconjugated hyperbilirubinemia
```
Hemolytic anemia
Physiologic jaundice
Crigler-najjar syndrome types I and II
Gilbert syndrome
Toxic hyperbilirubinemia
```
2852
Examples of conjugated hyperbilirubinemia
Biliary tree obstruction
Dubin-Johnson syndrome
Rotor syndrome
2853
What reaction measures total and direct bilirubin?
Van den bergs reaction
2854
What enzyme activates fatty acid for metabolism use?
Fatty-acyl-CoA synthetase
2855
Cofactor required for fatty acid activation
Vitamin B5 or Panthotenic acid
2856
Energy required to activate fatty acid
2 ATP
2857
What is the product formed in fatty acid synthesis?
Palmitate (16:0)
2858
Where does fatty acid synthesis occur?
Cytosol
Major: Liver and lactating mammary glands
Minor: adipose tissue
2859
Substrates for fatty acid synthesis
1 acetyl CoA
7 malonyl CoA
NADPH
ATP
2860
Rate limiting step in fatty acid synthesis
Acetyl CoA + ATP -> malonyl CoA
| Enzyme: acetyl CoA carboxylase
2861
Steps in fatty acid synthesis
1. Synthesis of cytoplasmic acetyl CoA (transfer of mitochondrial acetyl CoA to cytoplasm via citrate shuttle)
2. Acetyl CoA carboxylation to malonyl CoA (via acetyl CoA carboxylase with biotin) [+ insulin, citrate]
3. Assembly of palmitate (via fatty acid synthase and Vit B5)
2862
Steps in palmitate assembly
1. Condensation
2. Reduction
3. Dehydration
4. Reduction
2863
What is the fate of Palmitate after its production?
1. Further elongation in SER and mitochondria
| 2. Desaturated in the ER (but not past the 9th carbon)
2864
Main storage form of fatty acids
Triacylglycerols
2865
Where does TAG synthesis occur?
Liver and adipose tissue
2866
Sources of glycerol-3-phosphate
1. DHAP from glycolysis (liver and adipose)
| 2. Phosphorylation of free glycerol (liver)
2867
What enzyme is responsible for the release of free fatty acids from TAGs?
Hormone sensitive lipases
2868
In the bloodstream fatty acids are always bound to?
Albumin
2869
Hormone sensitive lipases can only release what free fatty acids stored in TAG?
C1 & 3 thus resulting in
TAG -> 2 free FA and 2-mono acyl glycerol
2870
Where does B-oxidation of fatty acids occur
Mitochondria of all cells, but the fatty acid activation raft occurs in the Cytosol
Exception: RBC, kidney medulla, neurons, testes
2871
Rate limiting step in B-oxidation
Fatty acyl CoA + carnitine -> fatty acyl carnitine + CoA
| Enzyme: carnitine acyl transferase I
2872
Cutoff number of carbons that do not need a shuttle
Less than 12 carbons
2873
Steps in the carnitine shuttle
1. Fatty acyl synthase activates the fatty acid
2. Carnitine acyl transferase 1 attaches to fatty acyl to carnitine in the outer mitochondrial membrane
3. Fatty acyl-carnitine is shuttle through the inner membrane
4. Carnitine acyl transferase-2 transfers fatty acyl group back to a CoA in the mitochondrial matrix
2874
Steps in beta oxidation
1. Oxidation
2. Hydratiion
3. Oxidation
4. Thiolysis
2875
Beta oxidation of fatty acids with an odd number of carbon atoms releases?
Propionyl CoA which is converted to methylmalonyl coa (requires B12) then to succinyl CoA
2876
Which is responsible for the conversion of very long chain fatty acids?
Peroxisomes but if unsaturated it requires 3,2 enol-CoA isomerase
2877
Energy yield in ATP of beta oxidation of palmitate
129 ATP
7 NADH= 21
7 FAD= 14
8 acetyl CoA= 96
Activation = -2
2878
Intake of this compound depletes the body's NAD+ supply leading to accumulation Of fat in the liver
Alcohol
2879
Type of carnitine deficiency which leads to impaired FA oxidation and ketogenesis with hypoglycemia?
CPT-1 deficiency
2880
Type of carnitine deficiency which affects skeletal muscle and when severe the liver
CPT-2 deficiency
2881
It is a disorder school results in decreased fatty acid oxidation. Without the ATP to support gluconeogenesis, hypoglycemia becomes profound which may eventually leads to SIDS. It is prevented by frequent feeding with high carbohydrate and low fat diet.
Medium-chain fatty acyl-CoA dehydrogenase (MCAD) deficiency
2882
Associated with eating unripe fruit of the akee tree which contains hypoglycin thus activating MC and SC acyl CoA dehydrogenase
Jamaican vomiting sickness
2883
Rare neurological disorder which results to the accumulation of phytanic acid found in plant food stuff which blocks Boxidation
Refsum disease
2884
Cerebrohepatorenal syndrome resulting from the absence of peroxisomes in all tissues, it is characterized by liver dysfunction, jaundice, MR, weakness, hypotonia, and craniofacial dimorphism
Zellweger syndrome
2885
Defect in peroxismal activation of VLCFA thus leading to its accumulation. Ssx: apathy, behavral change, then visual loss spasticity, ataxia. All due to the fact since VLCFA are found in myelin tissue.
X-lied adrenoleukodystrophy
2886
Where does ketogenesis occur?
Liver mitochondria
2887
Products of ketogenesis
Acetoacetate and B-hydroxybutyrate (fuel)
| Acetone (cannot be used as fuel)
2888
Rate limiting step of ketogenesis
Acetoacetyl CoA + acetyl CoA --(HMG CoA synthase)--> HMG CoA
2889
What are the initial products that lead to the formation of acetyl CoA in ketogenolysis?
B-hydroxybutyrate -> acetoacetate -> acetyl coa
2890
What peripheral tissues can oxidize ketone bodes?
Those with mitochondria like the renal cortex, brain, and skeletal muscle
2891
Why cant liver convert acetoacetate to acetyl CoA?
It lacks succinyl-CoA acetoacetyl-CoA reductase (thiophorase)
2892
What is the Urine test for ketones? What ketone type does not it detect?
Nitroprusside test
Does not detect b-hydroxybutyrate
2893
Which part of cholesterol can a fatty acid attach to form a cholesteryl ester?
Single hydroxyl group of carbon 3 of the alpha ring
2894
Where does cholesterol synthesis occur?
All cells in the Cytosol and SER majority of which are found in the liver and intestines
2895
Substrates of cholesterol synthesis
Acetyl CoA, NADPH, ATP
2896
Rate limiting step in cholesterol synthesis
HMG CoA --(HMG CoA reductase)--> mevalonate
2897
Steps in Cholestid synthesis
1. Biosynthesis of mevalonate
2. Formation of isoprenoid units
3. Isoprene unit is formed from 6 isoprenoid units
4. Formation of lanosterol
5. Formation of cholesterol
2898
How is the cholesterol ring eliminated?
Through conversion to bile salts then secretion to bile
2899
Bile acid synthesis, found in the liver and Cytosol, rate limiting enzyme is?
Cholesterol-7-a-hydroxylase
2900
What are the primary bile acids?
Cholic acid
| Chenocholic acid
2901
What are the two amino acids used in bile acid conjugation to form bile salts?
Taurine and glycine
2902
What are the secondary bile acids?
Deoxycholic acid
| Lithocholic acid
2903
Where does steroid hormone synthesis occur?
SER of the adrenal glands, ovaries and testes, and placenta
2904
What is blocked by the drug aminogluthetimide?
The conversion of cholesterol to pregnenolone by desmolase
2905
The enzyme responsible for the breakdown of TAG to FA and:
A) 2-MAG from diet
B) FREE glycerol from chylomicrons and VLDL
C) 2-MAG from adipose
A) pancreatic lipase
B) Lipoprotein lipase
C) hormone sensitive lipase
2906
Lipoprotein with the largest percentage of TG
Chylomicrons
2907
Lipoprotein with the largest percentage of cholesteryl esters
LDL
2908
Chylomicrons transport TG and cholesterol from where to where?
Intestines to tissues
2909
VLDL transports TG from where to where?
Liver to tissues
2910
What apoprotein activates lipoprotein lipase?
APO-CII
2911
What apolipoprotein uptakes remnants by the liver?
APO E
2912
Apolipoprotein B-48 is used by chylomicrons which are created by the?
Epithelial cells
2913
What apolipoprotein is secreted by the liver for VDL?
B-100
2914
How does IDL become LDL?
By picking up cholesterol from HD!
2915
Which apoprotein delivers cholesterol into cells?
LDL
2916
Which apolipoprotein is used by HDL to activate lecithin cholesterol acyl transferase or LCAT to produce cholesterol esters?
APO-A1
2917
Difference between Type II familial hypercholesterolemia and type IV familial hypertriglyceredemia?
The former has high LDL leader to xanthomas and xanthelasmas with increased risk of atherosclerosis and CHD
The latter has increased VLDL production leading to a triad of
1. DM type 2
2. CAD
3. Obesity
2918
Phospholipid is composed of
DAG
Alcohol
Phosphodiester bond
2919
Most abundant phospholipid which is important in nervous transmission
Phosphatidylcholine
2920
Phospholipid playing a role in apoptosis
Phosphatidyl serine
2921
Phospholipid that is a major component of surfactant?
Dipalmitoylphosphatidylcholine
2922
Phospholipid reservoir for arachidonic acid in the membranes
Phosphatidylinositol
2923
What phospholipid is essential in mitochondrial function which is also used as a non-troponemal test due to its ability to act as an antigen?
Cardiolipin
2924
```
Composition of these glycolipids:
Ceramide
Cerebroside
Globoside
Ganglioside
Sulfatide
```
Ceramide: sphingosine + FA
```
Ceramide + ________
Glucose or galactose = Cerebroside
Oligosacchardide = Globoside
N-acetylneuramic acid = Ganglioside
Sulfated galactose = Sulfatide
```
2925
Hexosaminidase a ficiency leading to Ssx like cherry red macula, MR, hypotonia
Tay-Sachs disease
2926
A-galactosidase deficiency leading to 3Rs: recessive x-linked, rash, renal failure
Fabrys disease
2927
B-glucosidase deficiency leading to hepatosplenomegaly and erosion of long bones
Gauchers dissease
2928
Sphingomyelinase deficiency leading to hepatosplenomegaly
Nieman-pick disease
2929
The set of all proteins expressed by an individual at a particular time
Proteome
2930
Aims to identify the entire complement of proteins elaborated by a cell under diverse conditions
Proteomics
2931
What amino acid is needed to form ALA in heme synthesis?
Glycine combined with succinyl CoA
2932
Which amino acid carries nitrogen from the liver?
Alanine
2933
Which amino acids are implicated in maple syrup disease
valine, lucine, isoleucine
2934
What enzyme is responsible for the buildup of phenyl lactate, phenyl acetate, and phenylpyruvate?
Phenylalanine hydroxylase
2935
What amino acid is the precursor for niacin, serotonin, and melatonin?
Serotonin
2936
What is the amino acid precursor for homocysteine?
Methionine
2937
What amino acid contributes to the fibrous structure of collagen and interrupts a-helices in globular proteins?
Proline
2938
Increase of the combination of this Amino acid is responsible for the curly hair of people?
Cysteine + cysteine = cystine
2939
Amino acids with sites for O-linked glycosylation in the Golgi apparatus?
Serine and threonine
2940
Site for n-linked glycosylation in the ER
Asparagine
2941
Amino acid deaminated by an enzyme which results in the formation of ammonia. This is the major carrier of nitrogen to the liver from peripheral tissues,
Glutaminase deaminates glutamine
2942
Amino acid used in the determination for Folic acid deficiency. What is the test called?
Histidine used in the N-forminoglutamate excretion test
| Increased amounts of FIGu in urine by Folic acid deficient individuals after histindine intake
2943
Precursor amino acid for creatinine, urea, nitric oxide
Arginine
2944
Essential amino acids that cannot be synthesized by the body and must come from the diet
PVT TIM HALL always ARGues and never TYRes
Phenylalanine, valine, tryptophan, threonine' isoleucine, methionine, histidine, argenine, Leucine, Lysine
2945
Heme is a complex of?
Protoporphorin IX and heme
2946
What is the Bohr effect?
HBO2 + H+ HbH + O2
2947
What is an oxidized for of HB (Fe 3+) that does not bind O2 readily which could lead to chocolate cyanosis ? It is treated with oral methylene blue or ascorbic acid up to IV methylene blue.
Methemoglobin
2948
Hemoglobin bound to carbon monoxide instead of O2 leading to a cherry pink color.
Carboxyhemoglobin
2949
HB bound to carbon dioxide is called
Carbaminohenoglobin
2950
Classification of alpha and beta thalassemia
Alpha: silent carrier, a-thalassemia trait, Hb H disease, hydrops fetalis
Beta: B-thalassemia minor and major
2951
Most frequently affected collagen in Ehler Danlos syndrome leading to hyper extensible skin, tendency to bleed, hyper mobile joints, and increased risk for berry aneurysms.
Collagen type 3
2952
Collagen I mutation leading to bendable and easily fractured bones. Accompanied with blue sclerae, hearing loss, and dental imperfections.
Osteogenesis imperfecta
2953
Vitamin C deficiency leading to decreased hydroxylation of collagen. This leads to sore spongy gums, loose teeth, poor wound healing, and petecchiae on skin and mucous membranes.
Scurvy
2954
Type IV collagen defect leading to hematuria and ESRD
Alpert syndrome
2955
Collagen defect leading to kinky hair due to a deficiency of copper required by lysyl oxidase to strengthen collagen fibers.
Menke syndrome
2956
Skin breaking and blisters as a result for minor trauma. This disease is due to a defect in collage VII.
Epidermolysis bullosa
2957
Like collagen elastin has pro line and Lysine but has little and no?
Hydroxyproline
| Hydroxylysine
2958
Protein degradation mechanisms of nitrogen
Energy dependent ubiquitin-proteosome mechanism
| Non-energy dependent degradation enzyme
2959
Phases in amino acid catabolism
First phase: removal of a-amino group forming ammonia and a corresponding ketoacid
Second phase: carbon skeletons of a-ketoacids are converted to common intermediates of energy producing metabolic pathwas
2960
Two main steps in nitrogen removal from AA
1. Transamination
| 2. Oxidative deamination
2961
Where does transamination occur?
All cells of the body
2962
All but two amino acids transfer their amino groups to a-ketoglutarate except?
Lysine and threonine
2963
What is the coenzyme for the two aminotransferases?
Pyridoxal phosphate (vitamin B6)
2964
Oxidative deamination occurs where and for which amino acid only?
Liver and kidney
| Only glutamate
2965
Glutamate is oxidized by glutamate dehydrogenases and deaminated to form ?
free ammonia which is used to make urea
2966
What does the conversion of glutamate to a-ketoglutarate yield? What about vice versa?
Glutamate -> a ketoglutarate NH3 + NADH
| A ketoglutarate -> glutamate NADP+ + NH3
2967
How is excess nitrogen removal from peripheral tissues removed?
1. Glutamine: via glutamate + ammonia (through Flutamide synthaetase)
2. Alanine: via glucose -> pyruvate + glutamate -> alanine cycle
2968
Glutaminase deaminates glutamine to produce ammonium ion which is excreted from the body. Where are the two tissues this enzyme could be located?
Kidneys and small intestines
2969
Another name for urea cycle
Ornithine cycle or krebs-henseleit cycle
2970
What are the donors of the urea molecule?
1. NH3 from free ammonia
2. NH3 from aspartate
3. 1C and 1O from CO2
2971
Reactions in the urea cycle
1. Formation of carbamoyl phosphate (via carbamoyl phosphate synthetase I)
2. Formation of citrulline (via Ornithine transcarbamoylase)
3. Synthesis of arginosuccinate (arginosuccinate synthetase)
4. Cleavage of arginosuccinate to form arginine (Arginosuccinase)
5. Arginine cleavage to yield urea and Ornithine (arginase)
2972
Rate limiting step of urea cycle
Carbamoyl phosphate synthetase I
2973
Energy requirement of urea cycle
4 ATP
2974
Co factors of urea cycle
N-acetylglutamate
| Biotin
2975
Hereditary hyperammonemia produces symptoms such as
Hyperammonemia, elevated blood glutamine, decreased BUN
| Parents with lethargy, vomiting, hyperventilation, convulsions, cerebral edema, coma, and death
2976
Treatment for hereditary hyperammonemia
Low protein diet
| Administration of sodium benzoate or phenylpyruvate to capture and excrete excess nitrogen
2977
Ketogenic carbon skeletons of AA
Leucine
Lysine
Yields acetoacetate or acetyl-coa/ acetoacetyl-coa
2978
Ketogenic and glucogenic carbon skeletons of AA
```
WIFY
Phenylalanine
Isoleucine
Tryptophan
Tyrosine
```
Yields Ketogenic and glucose or glycogen by products
2979
This amino acid acts as a raw material in the biosynthesis of Heme, purines, creatine
Glycine
2980
This amino acid acts as a raw material in the biosynthesis of phospholipid, sphingolipid, purines, thymine
Serine
2981
This amino acid acts as a raw material in the biosynthesis of GABA
Glutamate
2982
This amino acid acts as a raw material in the biosynthesis of creatine, polyamines, nitric oxide
Arginine
2983
This amino acid acts as a raw material in the biosynthesis of serotonin, NAD+, NADP+, melatonin
Tryptophan
2984
This amino acid acts as a raw material in the biosynthesis of catecholamines, thyroid hormones, melanin
Tyrosine
2985
3 hormones dependent on tyrosine
Thyroid hormones
Melanin
Catecholamines
2986
Deficiency of homogenistic acid oxidase in the degrative pathway of tyrosine which results in urine turning to black on standing with dark connective tissues (ochronosis)
Alkaptonuria
2987
Congenital deficiency due tyrosinase deficieny or defective tyrosine transporters which leads to an increased risk for skin cancer.
Albinism
2988
Autosomal recessive disorder that may either be due to decreased methionine, increased cysteine, B6, and folate or decreased affinity for cystathione synthase. This results in mental retardation, osteoporosis, tall stature, lens subluxation, and atherosclerosis.
Homocystinuria
2989
Common inherited defect of renal tubular amino acid transporter for its parent compound, Ornithine, Lysine, and arginine, in the PCT of the kidneys. It eventually precipitates and cause staghorn caliculi. What is its treatment?
Cystinuria is treated with acetazolamide to alkalinize the urine
2990
The initial and last three steps of heme synthesis occurs in?
The mitochondria
2991
Heme synthesis summary
1. Formation of ALA (via ALA synthase and B6)
2. Formation of porphobilinogen
3. Formation of uroporphyrinogen
4. Formation of heme
2992
Lead inhibits what two steps in heme synthesis?
1. Introduction of Fe 2+ into protoporphyrin IX via ferrochelatase
2. Condensation of two ALA molecules by zinc containing ALA dehydratase
2993
Where is B6 a cofactors of?
1. Heme synthesis
2. Synthesis of cystathionine from homocysteine
3. Transamination between alanine and a-ketoglutarate
2994
Most common porphyria
Porphyria cutanea tarda
2995
Which part of heme synthesis do these symptoms appear?
1. Photosensitivity
2. Neuropsychiatric symptoms
1. After ring formation
| 2. Before ring formation
2996
Pyridoxine ficiency associated with isoniazid therapy results in this histopathologic finding
Sideroblastic anemia with ringed sideroblast
2997
Poisoning due to this heavy metal leads to coar basophilic stippling of RBC, peripheral neuropathy, lines in gums, increas in urinary ALA and free erythrocytes porphorin
lead poisoning
2998
Microcytic hypo chromic anemia is found in
IDA
Thalassemia
Lead poisoning
2999
Megaloblastic anemia is found in
Folate or B12 deficiency
| Pernicious anemia
3000
Normoyctic normochromic anemia is found in
Anemia of chronic kidney disease
| Blood loss
3001
Increase in MCHC is found in
Hereditary spherocytosis
3002
Summary of heme degradation
1. Formation of bilirubin
2. Uptake of bilirubin by the liver
3. Formation of bilirubin diglucoronide
4. Secretion of bilirubin into bile
5. Formation of urobilins in the intestine
3003
Colors of biliverdin, bilirubin, urobilinogen, stercolin, urobilin
```
Biliverdin: green
Bilirubin: red orange
Urobilinogen: colorless
Stercolin: brown orange red
Urobilin: yellow
```
3004
Examples of unconjugated hyperbilirubinemia
```
Hemolytic anemia
Physiologic jaundice
Crigler-najjar syndrome types I and II
Gilbert syndrome
Toxic hyperbilirubinemia
```
3005
Examples of conjugated hyperbilirubinemia
Biliary tree obstruction
Dubin-Johnson syndrome
Rotor syndrome
3006
What reaction measures total and direct bilirubin?
Van den bergs reaction
3007
What enzyme activates fatty acid for metabolism use?
Fatty-acyl-CoA synthetase
3008
Cofactor required for fatty acid activation
Vitamin B5 or Panthotenic acid
3009
Energy required to activate fatty acid
2 ATP
3010
What is the product formed in fatty acid synthesis?
Palmitate (16:0)
3011
Where does fatty acid synthesis occur?
Cytosol
Major: Liver and lactating mammary glands
Minor: adipose tissue
3012
Substrates for fatty acid synthesis
1 acetyl CoA
7 malonyl CoA
NADPH
ATP
3013
Rate limiting step in fatty acid synthesis
Acetyl CoA + ATP -> malonyl CoA
| Enzyme: acetyl CoA carboxylase
3014
Steps in fatty acid synthesis
1. Synthesis of cytoplasmic acetyl CoA (transfer of mitochondrial acetyl CoA to cytoplasm via citrate shuttle)
2. Acetyl CoA carboxylation to malonyl CoA (via acetyl CoA carboxylase with biotin) [+ insulin, citrate]
3. Assembly of palmitate (via fatty acid synthase and Vit B5)
3015
Steps in palmitate assembly
1. Condensation
2. Reduction
3. Dehydration
4. Reduction
3016
What is the fate of Palmitate after its production?
1. Further elongation in SER and mitochondria
| 2. Desaturated in the ER (but not past the 9th carbon)
3017
Main storage form of fatty acids
Triacylglycerols
3018
Where does TAG synthesis occur?
Liver and adipose tissue
3019
Sources of glycerol-3-phosphate
1. DHAP from glycolysis (liver and adipose)
| 2. Phosphorylation of free glycerol (liver)
3020
What enzyme is responsible for the release of free fatty acids from TAGs?
Hormone sensitive lipases
3021
In the bloodstream fatty acids are always bound to?
Albumin
3022
Hormone sensitive lipases can only release what free fatty acids stored in TAG?
C1 & 3 thus resulting in
TAG -> 2 free FA and 2-mono acyl glycerol
3023
Where does B-oxidation of fatty acids occur
Mitochondria of all cells, but the fatty acid activation raft occurs in the Cytosol
Exception: RBC, kidney medulla, neurons, testes
3024
Rate limiting step in B-oxidation
Fatty acyl CoA + carnitine -> fatty acyl carnitine + CoA
| Enzyme: carnitine acyl transferase I
3025
Cutoff number of carbons that do not need a shuttle
Less than 12 carbons
3026
Steps in the carnitine shuttle
1. Fatty acyl synthase activates the fatty acid
2. Carnitine acyl transferase 1 attaches to fatty acyl to carnitine in the outer mitochondrial membrane
3. Fatty acyl-carnitine is shuttle through the inner membrane
4. Carnitine acyl transferase-2 transfers fatty acyl group back to a CoA in the mitochondrial matrix
3027
Steps in beta oxidation
1. Oxidation
2. Hydratiion
3. Oxidation
4. Thiolysis
3028
Beta oxidation of fatty acids with an odd number of carbon atoms releases?
Propionyl CoA which is converted to methylmalonyl coa (requires B12) then to succinyl CoA
3029
Which is responsible for the conversion of very long chain fatty acids?
Peroxisomes but if unsaturated it requires 3,2 enol-CoA isomerase
3030
Energy yield in ATP of beta oxidation of palmitate
129 ATP
7 NADH= 21
7 FAD= 14
8 acetyl CoA= 96
Activation = -2
3031
Intake of this compound depletes the body's NAD+ supply leading to accumulation Of fat in the liver
Alcohol
3032
Type of carnitine deficiency which leads to impaired FA oxidation and ketogenesis with hypoglycemia?
CPT-1 deficiency
3033
Type of carnitine deficiency which affects skeletal muscle and when severe the liver
CPT-2 deficiency
3034
It is a disorder school results in decreased fatty acid oxidation. Without the ATP to support gluconeogenesis, hypoglycemia becomes profound which may eventually leads to SIDS. It is prevented by frequent feeding with high carbohydrate and low fat diet.
Medium-chain fatty acyl-CoA dehydrogenase (MCAD) deficiency
3035
Associated with eating unripe fruit of the akee tree which contains hypoglycin thus activating MC and SC acyl CoA dehydrogenase
Jamaican vomiting sickness
3036
Rare neurological disorder which results to the accumulation of phytanic acid found in plant food stuff which blocks Boxidation
Refsum disease
3037
Cerebrohepatorenal syndrome resulting from the absence of peroxisomes in all tissues, it is characterized by liver dysfunction, jaundice, MR, weakness, hypotonia, and craniofacial dimorphism
Zellweger syndrome
3038
Defect in peroxismal activation of VLCFA thus leading to its accumulation. Ssx: apathy, behavral change, then visual loss spasticity, ataxia. All due to the fact since VLCFA are found in myelin tissue.
X-lied adrenoleukodystrophy
3039
Where does ketogenesis occur?
Liver mitochondria
3040
Products of ketogenesis
Acetoacetate and B-hydroxybutyrate (fuel)
| Acetone (cannot be used as fuel)
3041
Rate limiting step of ketogenesis
Acetoacetyl CoA + acetyl CoA --(HMG CoA synthase)--> HMG CoA
3042
What are the initial products that lead to the formation of acetyl CoA in ketogenolysis?
B-hydroxybutyrate -> acetoacetate -> acetyl coa
3043
What peripheral tissues can oxidize ketone bodes?
Those with mitochondria like the renal cortex, brain, and skeletal muscle
3044
Why cant liver convert acetoacetate to acetyl CoA?
It lacks succinyl-CoA acetoacetyl-CoA reductase (thiophorase)
3045
What is the Urine test for ketones? What ketone type does not it detect?
Nitroprusside test
Does not detect b-hydroxybutyrate
3046
Which part of cholesterol can a fatty acid attach to form a cholesteryl ester?
Single hydroxyl group of carbon 3 of the alpha ring
3047
Where does cholesterol synthesis occur?
All cells in the Cytosol and SER majority of which are found in the liver and intestines
3048
Substrates of cholesterol synthesis
Acetyl CoA, NADPH, ATP
3049
Rate limiting step in cholesterol synthesis
HMG CoA --(HMG CoA reductase)--> mevalonate
3050
Steps in Cholestid synthesis
1. Biosynthesis of mevalonate
2. Formation of isoprenoid units
3. Isoprene unit is formed from 6 isoprenoid units
4. Formation of lanosterol
5. Formation of cholesterol
3051
How is the cholesterol ring eliminated?
Through conversion to bile salts then secretion to bile
3052
Bile acid synthesis, found in the liver and Cytosol, rate limiting enzyme is?
Cholesterol-7-a-hydroxylase
3053
What are the primary bile acids?
Cholic acid
| Chenocholic acid
3054
What are the two amino acids used in bile acid conjugation to form bile salts?
Taurine and glycine
3055
What are the secondary bile acids?
Deoxycholic acid
| Lithocholic acid
3056
Where does steroid hormone synthesis occur?
SER of the adrenal glands, ovaries and testes, and placenta
3057
What is blocked by the drug aminogluthetimide?
The conversion of cholesterol to pregnenolone by desmolase
3058
The enzyme responsible for the breakdown of TAG to FA and:
A) 2-MAG from diet
B) FREE glycerol from chylomicrons and VLDL
C) 2-MAG from adipose
A) pancreatic lipase
B) Lipoprotein lipase
C) hormone sensitive lipase
3059
Lipoprotein with the largest percentage of TG
Chylomicrons
3060
Lipoprotein with the largest percentage of cholesteryl esters
LDL
3061
Chylomicrons transport TG and cholesterol from where to where?
Intestines to tissues
3062
VLDL transports TG from where to where?
Liver to tissues
3063
What apoprotein activates lipoprotein lipase?
APO-CII
3064
What apolipoprotein uptakes remnants by the liver?
APO E
3065
Apolipoprotein B-48 is used by chylomicrons which are created by the?
Epithelial cells
3066
What apolipoprotein is secreted by the liver for VDL?
B-100
3067
How does IDL become LDL?
By picking up cholesterol from HD!
3068
Which apoprotein delivers cholesterol into cells?
LDL
3069
Which apolipoprotein is used by HDL to activate lecithin cholesterol acyl transferase or LCAT to produce cholesterol esters?
APO-A1
3070
Difference between Type II familial hypercholesterolemia and type IV familial hypertriglyceredemia?
The former has high LDL leader to xanthomas and xanthelasmas with increased risk of atherosclerosis and CHD
The latter has increased VLDL production leading to a triad of
1. DM type 2
2. CAD
3. Obesity
3071
Phospholipid is composed of
DAG
Alcohol
Phosphodiester bond
3072
Most abundant phospholipid which is important in nervous transmission
Phosphatidylcholine
3073
Phospholipid playing a role in apoptosis
Phosphatidyl serine
3074
Phospholipid that is a major component of surfactant?
Dipalmitoylphosphatidylcholine
3075
Phospholipid reservoir for arachidonic acid in the membranes
Phosphatidylinositol
3076
What phospholipid is essential in mitochondrial function which is also used as a non-troponemal test due to its ability to act as an antigen?
Cardiolipin
3077
```
Composition of these glycolipids:
Ceramide
Cerebroside
Globoside
Ganglioside
Sulfatide
```
Ceramide: sphingosine + FA
```
Ceramide + ________
Glucose or galactose = Cerebroside
Oligosacchardide = Globoside
N-acetylneuramic acid = Ganglioside
Sulfated galactose = Sulfatide
```
3078
Hexosaminidase a ficiency leading to Ssx like cherry red macula, MR, hypotonia
Tay-Sachs disease
3079
A-galactosidase deficiency leading to 3Rs: recessive x-linked, rash, renal failure
Fabrys disease
3080
B-glucosidase deficiency leading to hepatosplenomegaly and erosion of long bones
Gauchers dissease
3081
Sphingomyelinase deficiency leading to hepatosplenomegaly
Nieman-pick disease
3082
The set of all proteins expressed by an individual at a particular time
Proteome
3083
Aims to identify the entire complement of proteins elaborated by a cell under diverse conditions
Proteomics
3084
What amino acid is needed to form ALA in heme synthesis?
Glycine combined with succinyl CoA
3085
Which amino acid carries nitrogen from the liver?
Alanine
3086
Which amino acids are implicated in maple syrup disease
valine, lucine, isoleucine
3087
What enzyme is responsible for the buildup of phenyl lactate, phenyl acetate, and phenylpyruvate?
Phenylalanine hydroxylase
3088
What amino acid is the precursor for niacin, serotonin, and melatonin?
Serotonin
3089
What is the amino acid precursor for homocysteine?
Methionine
3090
What amino acid contributes to the fibrous structure of collagen and interrupts a-helices in globular proteins?
Proline
3091
Increase of the combination of this Amino acid is responsible for the curly hair of people?
Cysteine + cysteine = cystine
3092
Amino acids with sites for O-linked glycosylation in the Golgi apparatus?
Serine and threonine
3093
Site for n-linked glycosylation in the ER
Asparagine
3094
Amino acid deaminated by an enzyme which results in the formation of ammonia. This is the major carrier of nitrogen to the liver from peripheral tissues,
Glutaminase deaminates glutamine
3095
Amino acid used in the determination for Folic acid deficiency. What is the test called?
Histidine used in the N-forminoglutamate excretion test
| Increased amounts of FIGu in urine by Folic acid deficient individuals after histindine intake
3096
Precursor amino acid for creatinine, urea, nitric oxide
Arginine
3097
Essential amino acids that cannot be synthesized by the body and must come from the diet
PVT TIM HALL always ARGues and never TYRes
Phenylalanine, valine, tryptophan, threonine' isoleucine, methionine, histidine, argenine, Leucine, Lysine
3098
Heme is a complex of?
Protoporphorin IX and heme
3099
What is the Bohr effect?
HBO2 + H+ HbH + O2
3100
What is an oxidized for of HB (Fe 3+) that does not bind O2 readily which could lead to chocolate cyanosis ? It is treated with oral methylene blue or ascorbic acid up to IV methylene blue.
Methemoglobin
3101
Hemoglobin bound to carbon monoxide instead of O2 leading to a cherry pink color.
Carboxyhemoglobin
3102
HB bound to carbon dioxide is called
Carbaminohenoglobin
3103
Classification of alpha and beta thalassemia
Alpha: silent carrier, a-thalassemia trait, Hb H disease, hydrops fetalis
Beta: B-thalassemia minor and major
3104
Most frequently affected collagen in Ehler Danlos syndrome leading to hyper extensible skin, tendency to bleed, hyper mobile joints, and increased risk for berry aneurysms.
Collagen type 3
3105
Collagen I mutation leading to bendable and easily fractured bones. Accompanied with blue sclerae, hearing loss, and dental imperfections.
Osteogenesis imperfecta
3106
Vitamin C deficiency leading to decreased hydroxylation of collagen. This leads to sore spongy gums, loose teeth, poor wound healing, and petecchiae on skin and mucous membranes.
Scurvy
3107
Type IV collagen defect leading to hematuria and ESRD
Alpert syndrome
3108
Collagen defect leading to kinky hair due to a deficiency of copper required by lysyl oxidase to strengthen collagen fibers.
Menke syndrome
3109
Skin breaking and blisters as a result for minor trauma. This disease is due to a defect in collage VII.
Epidermolysis bullosa
3110
Like collagen elastin has pro line and Lysine but has little and no?
Hydroxyproline
| Hydroxylysine
3111
Protein degradation mechanisms of nitrogen
Energy dependent ubiquitin-proteosome mechanism
| Non-energy dependent degradation enzyme
3112
Phases in amino acid catabolism
First phase: removal of a-amino group forming ammonia and a corresponding ketoacid
Second phase: carbon skeletons of a-ketoacids are converted to common intermediates of energy producing metabolic pathwas
3113
Two main steps in nitrogen removal from AA
1. Transamination
| 2. Oxidative deamination
3114
Where does transamination occur?
All cells of the body
3115
All but two amino acids transfer their amino groups to a-ketoglutarate except?
Lysine and threonine
3116
What is the coenzyme for the two aminotransferases?
Pyridoxal phosphate (vitamin B6)
3117
Oxidative deamination occurs where and for which amino acid only?
Liver and kidney
| Only glutamate
3118
Glutamate is oxidized by glutamate dehydrogenases and deaminated to form ?
free ammonia which is used to make urea
3119
What does the conversion of glutamate to a-ketoglutarate yield? What about vice versa?
Glutamate -> a ketoglutarate NH3 + NADH
| A ketoglutarate -> glutamate NADP+ + NH3
3120
How is excess nitrogen removal from peripheral tissues removed?
1. Glutamine: via glutamate + ammonia (through Flutamide synthaetase)
2. Alanine: via glucose -> pyruvate + glutamate -> alanine cycle
3121
Glutaminase deaminates glutamine to produce ammonium ion which is excreted from the body. Where are the two tissues this enzyme could be located?
Kidneys and small intestines
3122
Another name for urea cycle
Ornithine cycle or krebs-henseleit cycle
3123
What are the donors of the urea molecule?
1. NH3 from free ammonia
2. NH3 from aspartate
3. 1C and 1O from CO2
3124
Reactions in the urea cycle
1. Formation of carbamoyl phosphate (via carbamoyl phosphate synthetase I)
2. Formation of citrulline (via Ornithine transcarbamoylase)
3. Synthesis of arginosuccinate (arginosuccinate synthetase)
4. Cleavage of arginosuccinate to form arginine (Arginosuccinase)
5. Arginine cleavage to yield urea and Ornithine (arginase)
3125
Rate limiting step of urea cycle
Carbamoyl phosphate synthetase I
3126
Energy requirement of urea cycle
4 ATP
3127
Co factors of urea cycle
N-acetylglutamate
| Biotin
3128
Hereditary hyperammonemia produces symptoms such as
Hyperammonemia, elevated blood glutamine, decreased BUN
| Parents with lethargy, vomiting, hyperventilation, convulsions, cerebral edema, coma, and death
3129
Treatment for hereditary hyperammonemia
Low protein diet
| Administration of sodium benzoate or phenylpyruvate to capture and excrete excess nitrogen
3130
Ketogenic carbon skeletons of AA
Leucine
Lysine
Yields acetoacetate or acetyl-coa/ acetoacetyl-coa
3131
Ketogenic and glucogenic carbon skeletons of AA
```
WIFY
Phenylalanine
Isoleucine
Tryptophan
Tyrosine
```
Yields Ketogenic and glucose or glycogen by products
3132
This amino acid acts as a raw material in the biosynthesis of Heme, purines, creatine
Glycine
3133
This amino acid acts as a raw material in the biosynthesis of phospholipid, sphingolipid, purines, thymine
Serine
3134
This amino acid acts as a raw material in the biosynthesis of GABA
Glutamate
3135
This amino acid acts as a raw material in the biosynthesis of creatine, polyamines, nitric oxide
Arginine
3136
This amino acid acts as a raw material in the biosynthesis of serotonin, NAD+, NADP+, melatonin
Tryptophan
3137
This amino acid acts as a raw material in the biosynthesis of catecholamines, thyroid hormones, melanin
Tyrosine
3138
3 hormones dependent on tyrosine
Thyroid hormones
Melanin
Catecholamines
3139
Deficiency of homogenistic acid oxidase in the degrative pathway of tyrosine which results in urine turning to black on standing with dark connective tissues (ochronosis)
Alkaptonuria
3140
Congenital deficiency due tyrosinase deficieny or defective tyrosine transporters which leads to an increased risk for skin cancer.
Albinism
3141
Autosomal recessive disorder that may either be due to decreased methionine, increased cysteine, B6, and folate or decreased affinity for cystathione synthase. This results in mental retardation, osteoporosis, tall stature, lens subluxation, and atherosclerosis.
Homocystinuria
3142
Common inherited defect of renal tubular amino acid transporter for its parent compound, Ornithine, Lysine, and arginine, in the PCT of the kidneys. It eventually precipitates and cause staghorn caliculi. What is its treatment?
Cystinuria is treated with acetazolamide to alkalinize the urine
3143
The initial and last three steps of heme synthesis occurs in?
The mitochondria
3144
Heme synthesis summary
1. Formation of ALA (via ALA synthase and B6)
2. Formation of porphobilinogen
3. Formation of uroporphyrinogen
4. Formation of heme
3145
Lead inhibits what two steps in heme synthesis?
1. Introduction of Fe 2+ into protoporphyrin IX via ferrochelatase
2. Condensation of two ALA molecules by zinc containing ALA dehydratase
3146
Where is B6 a cofactors of?
1. Heme synthesis
2. Synthesis of cystathionine from homocysteine
3. Transamination between alanine and a-ketoglutarate
3147
Most common porphyria
Porphyria cutanea tarda
3148
Which part of heme synthesis do these symptoms appear?
1. Photosensitivity
2. Neuropsychiatric symptoms
1. After ring formation
| 2. Before ring formation
3149
Pyridoxine ficiency associated with isoniazid therapy results in this histopathologic finding
Sideroblastic anemia with ringed sideroblast
3150
Poisoning due to this heavy metal leads to coar basophilic stippling of RBC, peripheral neuropathy, lines in gums, increas in urinary ALA and free erythrocytes porphorin
lead poisoning
3151
Microcytic hypo chromic anemia is found in
IDA
Thalassemia
Lead poisoning
3152
Megaloblastic anemia is found in
Folate or B12 deficiency
| Pernicious anemia
3153
Normoyctic normochromic anemia is found in
Anemia of chronic kidney disease
| Blood loss
3154
Increase in MCHC is found in
Hereditary spherocytosis
3155
Summary of heme degradation
1. Formation of bilirubin
2. Uptake of bilirubin by the liver
3. Formation of bilirubin diglucoronide
4. Secretion of bilirubin into bile
5. Formation of urobilins in the intestine
3156
Colors of biliverdin, bilirubin, urobilinogen, stercolin, urobilin
```
Biliverdin: green
Bilirubin: red orange
Urobilinogen: colorless
Stercolin: brown orange red
Urobilin: yellow
```
3157
Examples of unconjugated hyperbilirubinemia
```
Hemolytic anemia
Physiologic jaundice
Crigler-najjar syndrome types I and II
Gilbert syndrome
Toxic hyperbilirubinemia
```
3158
Examples of conjugated hyperbilirubinemia
Biliary tree obstruction
Dubin-Johnson syndrome
Rotor syndrome
3159
What reaction measures total and direct bilirubin?
Van den bergs reaction
3160
What enzyme activates fatty acid for metabolism use?
Fatty-acyl-CoA synthetase
3161
Cofactor required for fatty acid activation
Vitamin B5 or Panthotenic acid
3162
Energy required to activate fatty acid
2 ATP
3163
What is the product formed in fatty acid synthesis?
Palmitate (16:0)
3164
Where does fatty acid synthesis occur?
Cytosol
Major: Liver and lactating mammary glands
Minor: adipose tissue
3165
Substrates for fatty acid synthesis
1 acetyl CoA
7 malonyl CoA
NADPH
ATP
3166
Rate limiting step in fatty acid synthesis
Acetyl CoA + ATP -> malonyl CoA
| Enzyme: acetyl CoA carboxylase
3167
Steps in fatty acid synthesis
1. Synthesis of cytoplasmic acetyl CoA (transfer of mitochondrial acetyl CoA to cytoplasm via citrate shuttle)
2. Acetyl CoA carboxylation to malonyl CoA (via acetyl CoA carboxylase with biotin) [+ insulin, citrate]
3. Assembly of palmitate (via fatty acid synthase and Vit B5)
3168
Steps in palmitate assembly
1. Condensation
2. Reduction
3. Dehydration
4. Reduction
3169
What is the fate of Palmitate after its production?
1. Further elongation in SER and mitochondria
| 2. Desaturated in the ER (but not past the 9th carbon)
3170
Main storage form of fatty acids
Triacylglycerols
3171
Where does TAG synthesis occur?
Liver and adipose tissue
3172
Sources of glycerol-3-phosphate
1. DHAP from glycolysis (liver and adipose)
| 2. Phosphorylation of free glycerol (liver)
3173
What enzyme is responsible for the release of free fatty acids from TAGs?
Hormone sensitive lipases
3174
In the bloodstream fatty acids are always bound to?
Albumin
3175
Hormone sensitive lipases can only release what free fatty acids stored in TAG?
C1 & 3 thus resulting in
TAG -> 2 free FA and 2-mono acyl glycerol
3176
Where does B-oxidation of fatty acids occur
Mitochondria of all cells, but the fatty acid activation raft occurs in the Cytosol
Exception: RBC, kidney medulla, neurons, testes
3177
Rate limiting step in B-oxidation
Fatty acyl CoA + carnitine -> fatty acyl carnitine + CoA
| Enzyme: carnitine acyl transferase I
3178
Cutoff number of carbons that do not need a shuttle
Less than 12 carbons
3179
Steps in the carnitine shuttle
1. Fatty acyl synthase activates the fatty acid
2. Carnitine acyl transferase 1 attaches to fatty acyl to carnitine in the outer mitochondrial membrane
3. Fatty acyl-carnitine is shuttle through the inner membrane
4. Carnitine acyl transferase-2 transfers fatty acyl group back to a CoA in the mitochondrial matrix
3180
Steps in beta oxidation
1. Oxidation
2. Hydratiion
3. Oxidation
4. Thiolysis
3181
Beta oxidation of fatty acids with an odd number of carbon atoms releases?
Propionyl CoA which is converted to methylmalonyl coa (requires B12) then to succinyl CoA
3182
Which is responsible for the conversion of very long chain fatty acids?
Peroxisomes but if unsaturated it requires 3,2 enol-CoA isomerase
3183
Energy yield in ATP of beta oxidation of palmitate
129 ATP
7 NADH= 21
7 FAD= 14
8 acetyl CoA= 96
Activation = -2
3184
Intake of this compound depletes the body's NAD+ supply leading to accumulation Of fat in the liver
Alcohol
3185
Type of carnitine deficiency which leads to impaired FA oxidation and ketogenesis with hypoglycemia?
CPT-1 deficiency
3186
Type of carnitine deficiency which affects skeletal muscle and when severe the liver
CPT-2 deficiency
3187
It is a disorder school results in decreased fatty acid oxidation. Without the ATP to support gluconeogenesis, hypoglycemia becomes profound which may eventually leads to SIDS. It is prevented by frequent feeding with high carbohydrate and low fat diet.
Medium-chain fatty acyl-CoA dehydrogenase (MCAD) deficiency
3188
Associated with eating unripe fruit of the akee tree which contains hypoglycin thus activating MC and SC acyl CoA dehydrogenase
Jamaican vomiting sickness
3189
Rare neurological disorder which results to the accumulation of phytanic acid found in plant food stuff which blocks Boxidation
Refsum disease
3190
Cerebrohepatorenal syndrome resulting from the absence of peroxisomes in all tissues, it is characterized by liver dysfunction, jaundice, MR, weakness, hypotonia, and craniofacial dimorphism
Zellweger syndrome
3191
Defect in peroxismal activation of VLCFA thus leading to its accumulation. Ssx: apathy, behavral change, then visual loss spasticity, ataxia. All due to the fact since VLCFA are found in myelin tissue.
X-lied adrenoleukodystrophy
3192
Where does ketogenesis occur?
Liver mitochondria
3193
Products of ketogenesis
Acetoacetate and B-hydroxybutyrate (fuel)
| Acetone (cannot be used as fuel)
3194
Rate limiting step of ketogenesis
Acetoacetyl CoA + acetyl CoA --(HMG CoA synthase)--> HMG CoA
3195
What are the initial products that lead to the formation of acetyl CoA in ketogenolysis?
B-hydroxybutyrate -> acetoacetate -> acetyl coa
3196
What peripheral tissues can oxidize ketone bodes?
Those with mitochondria like the renal cortex, brain, and skeletal muscle
3197
Why cant liver convert acetoacetate to acetyl CoA?
It lacks succinyl-CoA acetoacetyl-CoA reductase (thiophorase)
3198
What is the Urine test for ketones? What ketone type does not it detect?
Nitroprusside test
Does not detect b-hydroxybutyrate
3199
Which part of cholesterol can a fatty acid attach to form a cholesteryl ester?
Single hydroxyl group of carbon 3 of the alpha ring
3200
Where does cholesterol synthesis occur?
All cells in the Cytosol and SER majority of which are found in the liver and intestines
3201
Substrates of cholesterol synthesis
Acetyl CoA, NADPH, ATP
3202
Rate limiting step in cholesterol synthesis
HMG CoA --(HMG CoA reductase)--> mevalonate
3203
Steps in Cholestid synthesis
1. Biosynthesis of mevalonate
2. Formation of isoprenoid units
3. Isoprene unit is formed from 6 isoprenoid units
4. Formation of lanosterol
5. Formation of cholesterol
3204
How is the cholesterol ring eliminated?
Through conversion to bile salts then secretion to bile
3205
Bile acid synthesis, found in the liver and Cytosol, rate limiting enzyme is?
Cholesterol-7-a-hydroxylase
3206
What are the primary bile acids?
Cholic acid
| Chenocholic acid
3207
What are the two amino acids used in bile acid conjugation to form bile salts?
Taurine and glycine
3208
What are the secondary bile acids?
Deoxycholic acid
| Lithocholic acid
3209
Where does steroid hormone synthesis occur?
SER of the adrenal glands, ovaries and testes, and placenta
3210
What is blocked by the drug aminogluthetimide?
The conversion of cholesterol to pregnenolone by desmolase
3211
The enzyme responsible for the breakdown of TAG to FA and:
A) 2-MAG from diet
B) FREE glycerol from chylomicrons and VLDL
C) 2-MAG from adipose
A) pancreatic lipase
B) Lipoprotein lipase
C) hormone sensitive lipase
3212
Lipoprotein with the largest percentage of TG
Chylomicrons
3213
Lipoprotein with the largest percentage of cholesteryl esters
LDL
3214
Chylomicrons transport TG and cholesterol from where to where?
Intestines to tissues
3215
VLDL transports TG from where to where?
Liver to tissues
3216
What apoprotein activates lipoprotein lipase?
APO-CII
3217
What apolipoprotein uptakes remnants by the liver?
APO E
3218
Apolipoprotein B-48 is used by chylomicrons which are created by the?
Epithelial cells
3219
What apolipoprotein is secreted by the liver for VDL?
B-100
3220
How does IDL become LDL?
By picking up cholesterol from HD!
3221
Which apoprotein delivers cholesterol into cells?
LDL
3222
Which apolipoprotein is used by HDL to activate lecithin cholesterol acyl transferase or LCAT to produce cholesterol esters?
APO-A1
3223
Difference between Type II familial hypercholesterolemia and type IV familial hypertriglyceredemia?
The former has high LDL leader to xanthomas and xanthelasmas with increased risk of atherosclerosis and CHD
The latter has increased VLDL production leading to a triad of
1. DM type 2
2. CAD
3. Obesity
3224
Phospholipid is composed of
DAG
Alcohol
Phosphodiester bond
3225
Most abundant phospholipid which is important in nervous transmission
Phosphatidylcholine
3226
Phospholipid playing a role in apoptosis
Phosphatidyl serine
3227
Phospholipid that is a major component of surfactant?
Dipalmitoylphosphatidylcholine
3228
Phospholipid reservoir for arachidonic acid in the membranes
Phosphatidylinositol
3229
What phospholipid is essential in mitochondrial function which is also used as a non-troponemal test due to its ability to act as an antigen?
Cardiolipin
3230
```
Composition of these glycolipids:
Ceramide
Cerebroside
Globoside
Ganglioside
Sulfatide
```
Ceramide: sphingosine + FA
```
Ceramide + ________
Glucose or galactose = Cerebroside
Oligosacchardide = Globoside
N-acetylneuramic acid = Ganglioside
Sulfated galactose = Sulfatide
```
3231
Hexosaminidase a ficiency leading to Ssx like cherry red macula, MR, hypotonia
Tay-Sachs disease
3232
A-galactosidase deficiency leading to 3Rs: recessive x-linked, rash, renal failure
Fabrys disease
3233
B-glucosidase deficiency leading to hepatosplenomegaly and erosion of long bones
Gauchers dissease
3234
Sphingomyelinase deficiency leading to hepatosplenomegaly
Nieman-pick disease
3235
The set of all proteins expressed by an individual at a particular time
Proteome
3236
Aims to identify the entire complement of proteins elaborated by a cell under diverse conditions
Proteomics
3237
What amino acid is needed to form ALA in heme synthesis?
Glycine combined with succinyl CoA
3238
Which amino acid carries nitrogen from the liver?
Alanine
3239
Which amino acids are implicated in maple syrup disease
valine, lucine, isoleucine
3240
What enzyme is responsible for the buildup of phenyl lactate, phenyl acetate, and phenylpyruvate?
Phenylalanine hydroxylase
3241
What amino acid is the precursor for niacin, serotonin, and melatonin?
Serotonin
3242
What is the amino acid precursor for homocysteine?
Methionine
3243
What amino acid contributes to the fibrous structure of collagen and interrupts a-helices in globular proteins?
Proline
3244
Increase of the combination of this Amino acid is responsible for the curly hair of people?
Cysteine + cysteine = cystine
3245
Amino acids with sites for O-linked glycosylation in the Golgi apparatus?
Serine and threonine
3246
Site for n-linked glycosylation in the ER
Asparagine
3247
Amino acid deaminated by an enzyme which results in the formation of ammonia. This is the major carrier of nitrogen to the liver from peripheral tissues,
Glutaminase deaminates glutamine
3248
Amino acid used in the determination for Folic acid deficiency. What is the test called?
Histidine used in the N-forminoglutamate excretion test
| Increased amounts of FIGu in urine by Folic acid deficient individuals after histindine intake
3249
Precursor amino acid for creatinine, urea, nitric oxide
Arginine
3250
Essential amino acids that cannot be synthesized by the body and must come from the diet
PVT TIM HALL always ARGues and never TYRes
Phenylalanine, valine, tryptophan, threonine' isoleucine, methionine, histidine, argenine, Leucine, Lysine
3251
Heme is a complex of?
Protoporphorin IX and heme
3252
What is the Bohr effect?
HBO2 + H+ HbH + O2
3253
What is an oxidized for of HB (Fe 3+) that does not bind O2 readily which could lead to chocolate cyanosis ? It is treated with oral methylene blue or ascorbic acid up to IV methylene blue.
Methemoglobin
3254
Hemoglobin bound to carbon monoxide instead of O2 leading to a cherry pink color.
Carboxyhemoglobin
3255
HB bound to carbon dioxide is called
Carbaminohenoglobin
3256
Classification of alpha and beta thalassemia
Alpha: silent carrier, a-thalassemia trait, Hb H disease, hydrops fetalis
Beta: B-thalassemia minor and major
3257
Most frequently affected collagen in Ehler Danlos syndrome leading to hyper extensible skin, tendency to bleed, hyper mobile joints, and increased risk for berry aneurysms.
Collagen type 3
3258
Collagen I mutation leading to bendable and easily fractured bones. Accompanied with blue sclerae, hearing loss, and dental imperfections.
Osteogenesis imperfecta
3259
Vitamin C deficiency leading to decreased hydroxylation of collagen. This leads to sore spongy gums, loose teeth, poor wound healing, and petecchiae on skin and mucous membranes.
Scurvy
3260
Type IV collagen defect leading to hematuria and ESRD
Alpert syndrome
3261
Collagen defect leading to kinky hair due to a deficiency of copper required by lysyl oxidase to strengthen collagen fibers.
Menke syndrome
3262
Skin breaking and blisters as a result for minor trauma. This disease is due to a defect in collage VII.
Epidermolysis bullosa
3263
Like collagen elastin has pro line and Lysine but has little and no?
Hydroxyproline
| Hydroxylysine
3264
Protein degradation mechanisms of nitrogen
Energy dependent ubiquitin-proteosome mechanism
| Non-energy dependent degradation enzyme
3265
Phases in amino acid catabolism
First phase: removal of a-amino group forming ammonia and a corresponding ketoacid
Second phase: carbon skeletons of a-ketoacids are converted to common intermediates of energy producing metabolic pathwas
3266
Two main steps in nitrogen removal from AA
1. Transamination
| 2. Oxidative deamination
3267
Where does transamination occur?
All cells of the body
3268
All but two amino acids transfer their amino groups to a-ketoglutarate except?
Lysine and threonine
3269
What is the coenzyme for the two aminotransferases?
Pyridoxal phosphate (vitamin B6)
3270
Oxidative deamination occurs where and for which amino acid only?
Liver and kidney
| Only glutamate
3271
Glutamate is oxidized by glutamate dehydrogenases and deaminated to form ?
free ammonia which is used to make urea
3272
What does the conversion of glutamate to a-ketoglutarate yield? What about vice versa?
Glutamate -> a ketoglutarate NH3 + NADH
| A ketoglutarate -> glutamate NADP+ + NH3
3273
How is excess nitrogen removal from peripheral tissues removed?
1. Glutamine: via glutamate + ammonia (through Flutamide synthaetase)
2. Alanine: via glucose -> pyruvate + glutamate -> alanine cycle
3274
Glutaminase deaminates glutamine to produce ammonium ion which is excreted from the body. Where are the two tissues this enzyme could be located?
Kidneys and small intestines
3275
Another name for urea cycle
Ornithine cycle or krebs-henseleit cycle
3276
What are the donors of the urea molecule?
1. NH3 from free ammonia
2. NH3 from aspartate
3. 1C and 1O from CO2
3277
Reactions in the urea cycle
1. Formation of carbamoyl phosphate (via carbamoyl phosphate synthetase I)
2. Formation of citrulline (via Ornithine transcarbamoylase)
3. Synthesis of arginosuccinate (arginosuccinate synthetase)
4. Cleavage of arginosuccinate to form arginine (Arginosuccinase)
5. Arginine cleavage to yield urea and Ornithine (arginase)
3278
Rate limiting step of urea cycle
Carbamoyl phosphate synthetase I
3279
Energy requirement of urea cycle
4 ATP
3280
Co factors of urea cycle
N-acetylglutamate
| Biotin
3281
Hereditary hyperammonemia produces symptoms such as
Hyperammonemia, elevated blood glutamine, decreased BUN
| Parents with lethargy, vomiting, hyperventilation, convulsions, cerebral edema, coma, and death
3282
Treatment for hereditary hyperammonemia
Low protein diet
| Administration of sodium benzoate or phenylpyruvate to capture and excrete excess nitrogen
3283
Ketogenic carbon skeletons of AA
Leucine
Lysine
Yields acetoacetate or acetyl-coa/ acetoacetyl-coa
3284
Ketogenic and glucogenic carbon skeletons of AA
```
WIFY
Phenylalanine
Isoleucine
Tryptophan
Tyrosine
```
Yields Ketogenic and glucose or glycogen by products
3285
This amino acid acts as a raw material in the biosynthesis of Heme, purines, creatine
Glycine
3286
This amino acid acts as a raw material in the biosynthesis of phospholipid, sphingolipid, purines, thymine
Serine
3287
This amino acid acts as a raw material in the biosynthesis of GABA
Glutamate
3288
This amino acid acts as a raw material in the biosynthesis of creatine, polyamines, nitric oxide
Arginine
3289
This amino acid acts as a raw material in the biosynthesis of serotonin, NAD+, NADP+, melatonin
Tryptophan
3290
This amino acid acts as a raw material in the biosynthesis of catecholamines, thyroid hormones, melanin
Tyrosine
3291
3 hormones dependent on tyrosine
Thyroid hormones
Melanin
Catecholamines
3292
Deficiency of homogenistic acid oxidase in the degrative pathway of tyrosine which results in urine turning to black on standing with dark connective tissues (ochronosis)
Alkaptonuria
3293
Congenital deficiency due tyrosinase deficieny or defective tyrosine transporters which leads to an increased risk for skin cancer.
Albinism
3294
Autosomal recessive disorder that may either be due to decreased methionine, increased cysteine, B6, and folate or decreased affinity for cystathione synthase. This results in mental retardation, osteoporosis, tall stature, lens subluxation, and atherosclerosis.
Homocystinuria
3295
Common inherited defect of renal tubular amino acid transporter for its parent compound, Ornithine, Lysine, and arginine, in the PCT of the kidneys. It eventually precipitates and cause staghorn caliculi. What is its treatment?
Cystinuria is treated with acetazolamide to alkalinize the urine
3296
The initial and last three steps of heme synthesis occurs in?
The mitochondria
3297
Heme synthesis summary
1. Formation of ALA (via ALA synthase and B6)
2. Formation of porphobilinogen
3. Formation of uroporphyrinogen
4. Formation of heme
3298
Lead inhibits what two steps in heme synthesis?
1. Introduction of Fe 2+ into protoporphyrin IX via ferrochelatase
2. Condensation of two ALA molecules by zinc containing ALA dehydratase
3299
Where is B6 a cofactors of?
1. Heme synthesis
2. Synthesis of cystathionine from homocysteine
3. Transamination between alanine and a-ketoglutarate
3300
Most common porphyria
Porphyria cutanea tarda
3301
Which part of heme synthesis do these symptoms appear?
1. Photosensitivity
2. Neuropsychiatric symptoms
1. After ring formation
| 2. Before ring formation
3302
Pyridoxine ficiency associated with isoniazid therapy results in this histopathologic finding
Sideroblastic anemia with ringed sideroblast
3303
Poisoning due to this heavy metal leads to coar basophilic stippling of RBC, peripheral neuropathy, lines in gums, increas in urinary ALA and free erythrocytes porphorin
lead poisoning
3304
Microcytic hypo chromic anemia is found in
IDA
Thalassemia
Lead poisoning
3305
Megaloblastic anemia is found in
Folate or B12 deficiency
| Pernicious anemia
3306
Normoyctic normochromic anemia is found in
Anemia of chronic kidney disease
| Blood loss
3307
Increase in MCHC is found in
Hereditary spherocytosis
3308
Summary of heme degradation
1. Formation of bilirubin
2. Uptake of bilirubin by the liver
3. Formation of bilirubin diglucoronide
4. Secretion of bilirubin into bile
5. Formation of urobilins in the intestine
3309
Colors of biliverdin, bilirubin, urobilinogen, stercolin, urobilin
```
Biliverdin: green
Bilirubin: red orange
Urobilinogen: colorless
Stercolin: brown orange red
Urobilin: yellow
```
3310
Examples of unconjugated hyperbilirubinemia
```
Hemolytic anemia
Physiologic jaundice
Crigler-najjar syndrome types I and II
Gilbert syndrome
Toxic hyperbilirubinemia
```
3311
Examples of conjugated hyperbilirubinemia
Biliary tree obstruction
Dubin-Johnson syndrome
Rotor syndrome
3312
What reaction measures total and direct bilirubin?
Van den bergs reaction
3313
What enzyme activates fatty acid for metabolism use?
Fatty-acyl-CoA synthetase
3314
Cofactor required for fatty acid activation
Vitamin B5 or Panthotenic acid
3315
Energy required to activate fatty acid
2 ATP
3316
What is the product formed in fatty acid synthesis?
Palmitate (16:0)
3317
Where does fatty acid synthesis occur?
Cytosol
Major: Liver and lactating mammary glands
Minor: adipose tissue
3318
Substrates for fatty acid synthesis
1 acetyl CoA
7 malonyl CoA
NADPH
ATP
3319
Rate limiting step in fatty acid synthesis
Acetyl CoA + ATP -> malonyl CoA
| Enzyme: acetyl CoA carboxylase
3320
Steps in fatty acid synthesis
1. Synthesis of cytoplasmic acetyl CoA (transfer of mitochondrial acetyl CoA to cytoplasm via citrate shuttle)
2. Acetyl CoA carboxylation to malonyl CoA (via acetyl CoA carboxylase with biotin) [+ insulin, citrate]
3. Assembly of palmitate (via fatty acid synthase and Vit B5)
3321
Steps in palmitate assembly
1. Condensation
2. Reduction
3. Dehydration
4. Reduction
3322
What is the fate of Palmitate after its production?
1. Further elongation in SER and mitochondria
| 2. Desaturated in the ER (but not past the 9th carbon)
3323
Main storage form of fatty acids
Triacylglycerols
3324
Where does TAG synthesis occur?
Liver and adipose tissue
3325
Sources of glycerol-3-phosphate
1. DHAP from glycolysis (liver and adipose)
| 2. Phosphorylation of free glycerol (liver)
3326
What enzyme is responsible for the release of free fatty acids from TAGs?
Hormone sensitive lipases
3327
In the bloodstream fatty acids are always bound to?
Albumin
3328
Hormone sensitive lipases can only release what free fatty acids stored in TAG?
C1 & 3 thus resulting in
TAG -> 2 free FA and 2-mono acyl glycerol
3329
Where does B-oxidation of fatty acids occur
Mitochondria of all cells, but the fatty acid activation raft occurs in the Cytosol
Exception: RBC, kidney medulla, neurons, testes
3330
Rate limiting step in B-oxidation
Fatty acyl CoA + carnitine -> fatty acyl carnitine + CoA
| Enzyme: carnitine acyl transferase I
3331
Cutoff number of carbons that do not need a shuttle
Less than 12 carbons
3332
Steps in the carnitine shuttle
1. Fatty acyl synthase activates the fatty acid
2. Carnitine acyl transferase 1 attaches to fatty acyl to carnitine in the outer mitochondrial membrane
3. Fatty acyl-carnitine is shuttle through the inner membrane
4. Carnitine acyl transferase-2 transfers fatty acyl group back to a CoA in the mitochondrial matrix
3333
Steps in beta oxidation
1. Oxidation
2. Hydratiion
3. Oxidation
4. Thiolysis
3334
Beta oxidation of fatty acids with an odd number of carbon atoms releases?
Propionyl CoA which is converted to methylmalonyl coa (requires B12) then to succinyl CoA
3335
Which is responsible for the conversion of very long chain fatty acids?
Peroxisomes but if unsaturated it requires 3,2 enol-CoA isomerase
3336
Energy yield in ATP of beta oxidation of palmitate
129 ATP
7 NADH= 21
7 FAD= 14
8 acetyl CoA= 96
Activation = -2
3337
Intake of this compound depletes the body's NAD+ supply leading to accumulation Of fat in the liver
Alcohol
3338
Type of carnitine deficiency which leads to impaired FA oxidation and ketogenesis with hypoglycemia?
CPT-1 deficiency
3339
Type of carnitine deficiency which affects skeletal muscle and when severe the liver
CPT-2 deficiency
3340
It is a disorder school results in decreased fatty acid oxidation. Without the ATP to support gluconeogenesis, hypoglycemia becomes profound which may eventually leads to SIDS. It is prevented by frequent feeding with high carbohydrate and low fat diet.
Medium-chain fatty acyl-CoA dehydrogenase (MCAD) deficiency
3341
Associated with eating unripe fruit of the akee tree which contains hypoglycin thus activating MC and SC acyl CoA dehydrogenase
Jamaican vomiting sickness
3342
Rare neurological disorder which results to the accumulation of phytanic acid found in plant food stuff which blocks Boxidation
Refsum disease
3343
Cerebrohepatorenal syndrome resulting from the absence of peroxisomes in all tissues, it is characterized by liver dysfunction, jaundice, MR, weakness, hypotonia, and craniofacial dimorphism
Zellweger syndrome
3344
Defect in peroxismal activation of VLCFA thus leading to its accumulation. Ssx: apathy, behavral change, then visual loss spasticity, ataxia. All due to the fact since VLCFA are found in myelin tissue.
X-lied adrenoleukodystrophy
3345
Where does ketogenesis occur?
Liver mitochondria
3346
Products of ketogenesis
Acetoacetate and B-hydroxybutyrate (fuel)
| Acetone (cannot be used as fuel)
3347
Rate limiting step of ketogenesis
Acetoacetyl CoA + acetyl CoA --(HMG CoA synthase)--> HMG CoA
3348
What are the initial products that lead to the formation of acetyl CoA in ketogenolysis?
B-hydroxybutyrate -> acetoacetate -> acetyl coa
3349
What peripheral tissues can oxidize ketone bodes?
Those with mitochondria like the renal cortex, brain, and skeletal muscle
3350
Why cant liver convert acetoacetate to acetyl CoA?
It lacks succinyl-CoA acetoacetyl-CoA reductase (thiophorase)
3351
What is the Urine test for ketones? What ketone type does not it detect?
Nitroprusside test
Does not detect b-hydroxybutyrate
3352
Which part of cholesterol can a fatty acid attach to form a cholesteryl ester?
Single hydroxyl group of carbon 3 of the alpha ring
3353
Where does cholesterol synthesis occur?
All cells in the Cytosol and SER majority of which are found in the liver and intestines
3354
Substrates of cholesterol synthesis
Acetyl CoA, NADPH, ATP
3355
Rate limiting step in cholesterol synthesis
HMG CoA --(HMG CoA reductase)--> mevalonate
3356
Steps in Cholestid synthesis
1. Biosynthesis of mevalonate
2. Formation of isoprenoid units
3. Isoprene unit is formed from 6 isoprenoid units
4. Formation of lanosterol
5. Formation of cholesterol
3357
How is the cholesterol ring eliminated?
Through conversion to bile salts then secretion to bile
3358
Bile acid synthesis, found in the liver and Cytosol, rate limiting enzyme is?
Cholesterol-7-a-hydroxylase
3359
What are the primary bile acids?
Cholic acid
| Chenocholic acid
3360
What are the two amino acids used in bile acid conjugation to form bile salts?
Taurine and glycine
3361
What are the secondary bile acids?
Deoxycholic acid
| Lithocholic acid
3362
Where does steroid hormone synthesis occur?
SER of the adrenal glands, ovaries and testes, and placenta
3363
What is blocked by the drug aminogluthetimide?
The conversion of cholesterol to pregnenolone by desmolase
3364
The enzyme responsible for the breakdown of TAG to FA and:
A) 2-MAG from diet
B) FREE glycerol from chylomicrons and VLDL
C) 2-MAG from adipose
A) pancreatic lipase
B) Lipoprotein lipase
C) hormone sensitive lipase
3365
Lipoprotein with the largest percentage of TG
Chylomicrons
3366
Lipoprotein with the largest percentage of cholesteryl esters
LDL
3367
Chylomicrons transport TG and cholesterol from where to where?
Intestines to tissues
3368
VLDL transports TG from where to where?
Liver to tissues
3369
What apoprotein activates lipoprotein lipase?
APO-CII
3370
What apolipoprotein uptakes remnants by the liver?
APO E
3371
Apolipoprotein B-48 is used by chylomicrons which are created by the?
Epithelial cells
3372
What apolipoprotein is secreted by the liver for VDL?
B-100
3373
How does IDL become LDL?
By picking up cholesterol from HD!
3374
Which apoprotein delivers cholesterol into cells?
LDL
3375
Which apolipoprotein is used by HDL to activate lecithin cholesterol acyl transferase or LCAT to produce cholesterol esters?
APO-A1
3376
Difference between Type II familial hypercholesterolemia and type IV familial hypertriglyceredemia?
The former has high LDL leader to xanthomas and xanthelasmas with increased risk of atherosclerosis and CHD
The latter has increased VLDL production leading to a triad of
1. DM type 2
2. CAD
3. Obesity
3377
Phospholipid is composed of
DAG
Alcohol
Phosphodiester bond
3378
Most abundant phospholipid which is important in nervous transmission
Phosphatidylcholine
3379
Phospholipid playing a role in apoptosis
Phosphatidyl serine
3380
Phospholipid that is a major component of surfactant?
Dipalmitoylphosphatidylcholine
3381
Phospholipid reservoir for arachidonic acid in the membranes
Phosphatidylinositol
3382
What phospholipid is essential in mitochondrial function which is also used as a non-troponemal test due to its ability to act as an antigen?
Cardiolipin
3383
```
Composition of these glycolipids:
Ceramide
Cerebroside
Globoside
Ganglioside
Sulfatide
```
Ceramide: sphingosine + FA
```
Ceramide + ________
Glucose or galactose = Cerebroside
Oligosacchardide = Globoside
N-acetylneuramic acid = Ganglioside
Sulfated galactose = Sulfatide
```
3384
Hexosaminidase a ficiency leading to Ssx like cherry red macula, MR, hypotonia
Tay-Sachs disease
3385
A-galactosidase deficiency leading to 3Rs: recessive x-linked, rash, renal failure
Fabrys disease
3386
B-glucosidase deficiency leading to hepatosplenomegaly and erosion of long bones
Gauchers dissease
3387
Sphingomyelinase deficiency leading to hepatosplenomegaly
Nieman-pick disease
3388
The set of all proteins expressed by an individual at a particular time
Proteome
3389
Aims to identify the entire complement of proteins elaborated by a cell under diverse conditions
Proteomics
3390
What amino acid is needed to form ALA in heme synthesis?
Glycine combined with succinyl CoA
3391
Which amino acid carries nitrogen from the liver?
Alanine
3392
Which amino acids are implicated in maple syrup disease
valine, lucine, isoleucine
3393
What enzyme is responsible for the buildup of phenyl lactate, phenyl acetate, and phenylpyruvate?
Phenylalanine hydroxylase
3394
What amino acid is the precursor for niacin, serotonin, and melatonin?
Serotonin
3395
What is the amino acid precursor for homocysteine?
Methionine
3396
What amino acid contributes to the fibrous structure of collagen and interrupts a-helices in globular proteins?
Proline
3397
Increase of the combination of this Amino acid is responsible for the curly hair of people?
Cysteine + cysteine = cystine
3398
Amino acids with sites for O-linked glycosylation in the Golgi apparatus?
Serine and threonine
3399
Site for n-linked glycosylation in the ER
Asparagine
3400
Amino acid deaminated by an enzyme which results in the formation of ammonia. This is the major carrier of nitrogen to the liver from peripheral tissues,
Glutaminase deaminates glutamine
3401
Amino acid used in the determination for Folic acid deficiency. What is the test called?
Histidine used in the N-forminoglutamate excretion test
| Increased amounts of FIGu in urine by Folic acid deficient individuals after histindine intake
3402
Precursor amino acid for creatinine, urea, nitric oxide
Arginine
3403
Essential amino acids that cannot be synthesized by the body and must come from the diet
PVT TIM HALL always ARGues and never TYRes
Phenylalanine, valine, tryptophan, threonine' isoleucine, methionine, histidine, argenine, Leucine, Lysine
3404
Heme is a complex of?
Protoporphorin IX and heme
3405
What is the Bohr effect?
HBO2 + H+ HbH + O2
3406
What is an oxidized for of HB (Fe 3+) that does not bind O2 readily which could lead to chocolate cyanosis ? It is treated with oral methylene blue or ascorbic acid up to IV methylene blue.
Methemoglobin
3407
Hemoglobin bound to carbon monoxide instead of O2 leading to a cherry pink color.
Carboxyhemoglobin
3408
HB bound to carbon dioxide is called
Carbaminohenoglobin
3409
Classification of alpha and beta thalassemia
Alpha: silent carrier, a-thalassemia trait, Hb H disease, hydrops fetalis
Beta: B-thalassemia minor and major
3410
Most frequently affected collagen in Ehler Danlos syndrome leading to hyper extensible skin, tendency to bleed, hyper mobile joints, and increased risk for berry aneurysms.
Collagen type 3
3411
Collagen I mutation leading to bendable and easily fractured bones. Accompanied with blue sclerae, hearing loss, and dental imperfections.
Osteogenesis imperfecta
3412
Vitamin C deficiency leading to decreased hydroxylation of collagen. This leads to sore spongy gums, loose teeth, poor wound healing, and petecchiae on skin and mucous membranes.
Scurvy
3413
Type IV collagen defect leading to hematuria and ESRD
Alpert syndrome
3414
Collagen defect leading to kinky hair due to a deficiency of copper required by lysyl oxidase to strengthen collagen fibers.
Menke syndrome
3415
Skin breaking and blisters as a result for minor trauma. This disease is due to a defect in collage VII.
Epidermolysis bullosa
3416
Like collagen elastin has pro line and Lysine but has little and no?
Hydroxyproline
| Hydroxylysine
3417
Protein degradation mechanisms of nitrogen
Energy dependent ubiquitin-proteosome mechanism
| Non-energy dependent degradation enzyme
3418
Phases in amino acid catabolism
First phase: removal of a-amino group forming ammonia and a corresponding ketoacid
Second phase: carbon skeletons of a-ketoacids are converted to common intermediates of energy producing metabolic pathwas
3419
Two main steps in nitrogen removal from AA
1. Transamination
| 2. Oxidative deamination
3420
Where does transamination occur?
All cells of the body
3421
All but two amino acids transfer their amino groups to a-ketoglutarate except?
Lysine and threonine
3422
What is the coenzyme for the two aminotransferases?
Pyridoxal phosphate (vitamin B6)
3423
Oxidative deamination occurs where and for which amino acid only?
Liver and kidney
| Only glutamate
3424
Glutamate is oxidized by glutamate dehydrogenases and deaminated to form ?
free ammonia which is used to make urea
3425
What does the conversion of glutamate to a-ketoglutarate yield? What about vice versa?
Glutamate -> a ketoglutarate NH3 + NADH
| A ketoglutarate -> glutamate NADP+ + NH3
3426
How is excess nitrogen removal from peripheral tissues removed?
1. Glutamine: via glutamate + ammonia (through Flutamide synthaetase)
2. Alanine: via glucose -> pyruvate + glutamate -> alanine cycle
3427
Glutaminase deaminates glutamine to produce ammonium ion which is excreted from the body. Where are the two tissues this enzyme could be located?
Kidneys and small intestines
3428
Another name for urea cycle
Ornithine cycle or krebs-henseleit cycle
3429
What are the donors of the urea molecule?
1. NH3 from free ammonia
2. NH3 from aspartate
3. 1C and 1O from CO2
3430
Reactions in the urea cycle
1. Formation of carbamoyl phosphate (via carbamoyl phosphate synthetase I)
2. Formation of citrulline (via Ornithine transcarbamoylase)
3. Synthesis of arginosuccinate (arginosuccinate synthetase)
4. Cleavage of arginosuccinate to form arginine (Arginosuccinase)
5. Arginine cleavage to yield urea and Ornithine (arginase)
3431
Rate limiting step of urea cycle
Carbamoyl phosphate synthetase I
3432
Energy requirement of urea cycle
4 ATP
3433
Co factors of urea cycle
N-acetylglutamate
| Biotin
3434
Hereditary hyperammonemia produces symptoms such as
Hyperammonemia, elevated blood glutamine, decreased BUN
| Parents with lethargy, vomiting, hyperventilation, convulsions, cerebral edema, coma, and death
3435
Treatment for hereditary hyperammonemia
Low protein diet
| Administration of sodium benzoate or phenylpyruvate to capture and excrete excess nitrogen
3436
Ketogenic carbon skeletons of AA
Leucine
Lysine
Yields acetoacetate or acetyl-coa/ acetoacetyl-coa
3437
Ketogenic and glucogenic carbon skeletons of AA
```
WIFY
Phenylalanine
Isoleucine
Tryptophan
Tyrosine
```
Yields Ketogenic and glucose or glycogen by products
3438
This amino acid acts as a raw material in the biosynthesis of Heme, purines, creatine
Glycine
3439
This amino acid acts as a raw material in the biosynthesis of phospholipid, sphingolipid, purines, thymine
Serine
3440
This amino acid acts as a raw material in the biosynthesis of GABA
Glutamate
3441
This amino acid acts as a raw material in the biosynthesis of creatine, polyamines, nitric oxide
Arginine
3442
This amino acid acts as a raw material in the biosynthesis of serotonin, NAD+, NADP+, melatonin
Tryptophan
3443
This amino acid acts as a raw material in the biosynthesis of catecholamines, thyroid hormones, melanin
Tyrosine
3444
3 hormones dependent on tyrosine
Thyroid hormones
Melanin
Catecholamines
3445
Deficiency of homogenistic acid oxidase in the degrative pathway of tyrosine which results in urine turning to black on standing with dark connective tissues (ochronosis)
Alkaptonuria
3446
Congenital deficiency due tyrosinase deficieny or defective tyrosine transporters which leads to an increased risk for skin cancer.
Albinism
3447
Autosomal recessive disorder that may either be due to decreased methionine, increased cysteine, B6, and folate or decreased affinity for cystathione synthase. This results in mental retardation, osteoporosis, tall stature, lens subluxation, and atherosclerosis.
Homocystinuria
3448
Common inherited defect of renal tubular amino acid transporter for its parent compound, Ornithine, Lysine, and arginine, in the PCT of the kidneys. It eventually precipitates and cause staghorn caliculi. What is its treatment?
Cystinuria is treated with acetazolamide to alkalinize the urine
3449
The initial and last three steps of heme synthesis occurs in?
The mitochondria
3450
Heme synthesis summary
1. Formation of ALA (via ALA synthase and B6)
2. Formation of porphobilinogen
3. Formation of uroporphyrinogen
4. Formation of heme
3451
Lead inhibits what two steps in heme synthesis?
1. Introduction of Fe 2+ into protoporphyrin IX via ferrochelatase
2. Condensation of two ALA molecules by zinc containing ALA dehydratase
3452
Where is B6 a cofactors of?
1. Heme synthesis
2. Synthesis of cystathionine from homocysteine
3. Transamination between alanine and a-ketoglutarate
3453
Most common porphyria
Porphyria cutanea tarda
3454
Which part of heme synthesis do these symptoms appear?
1. Photosensitivity
2. Neuropsychiatric symptoms
1. After ring formation
| 2. Before ring formation
3455
Pyridoxine ficiency associated with isoniazid therapy results in this histopathologic finding
Sideroblastic anemia with ringed sideroblast
3456
Poisoning due to this heavy metal leads to coar basophilic stippling of RBC, peripheral neuropathy, lines in gums, increas in urinary ALA and free erythrocytes porphorin
lead poisoning
3457
Microcytic hypo chromic anemia is found in
IDA
Thalassemia
Lead poisoning
3458
Megaloblastic anemia is found in
Folate or B12 deficiency
| Pernicious anemia
3459
Normoyctic normochromic anemia is found in
Anemia of chronic kidney disease
| Blood loss
3460
Increase in MCHC is found in
Hereditary spherocytosis
3461
Summary of heme degradation
1. Formation of bilirubin
2. Uptake of bilirubin by the liver
3. Formation of bilirubin diglucoronide
4. Secretion of bilirubin into bile
5. Formation of urobilins in the intestine
3462
Colors of biliverdin, bilirubin, urobilinogen, stercolin, urobilin
```
Biliverdin: green
Bilirubin: red orange
Urobilinogen: colorless
Stercolin: brown orange red
Urobilin: yellow
```
3463
Examples of unconjugated hyperbilirubinemia
```
Hemolytic anemia
Physiologic jaundice
Crigler-najjar syndrome types I and II
Gilbert syndrome
Toxic hyperbilirubinemia
```
3464
Examples of conjugated hyperbilirubinemia
Biliary tree obstruction
Dubin-Johnson syndrome
Rotor syndrome
3465
What reaction measures total and direct bilirubin?
Van den bergs reaction
3466
What enzyme activates fatty acid for metabolism use?
Fatty-acyl-CoA synthetase
3467
Cofactor required for fatty acid activation
Vitamin B5 or Panthotenic acid
3468
Energy required to activate fatty acid
2 ATP
3469
What is the product formed in fatty acid synthesis?
Palmitate (16:0)
3470
Where does fatty acid synthesis occur?
Cytosol
Major: Liver and lactating mammary glands
Minor: adipose tissue
3471
Substrates for fatty acid synthesis
1 acetyl CoA
7 malonyl CoA
NADPH
ATP
3472
Rate limiting step in fatty acid synthesis
Acetyl CoA + ATP -> malonyl CoA
| Enzyme: acetyl CoA carboxylase
3473
Steps in fatty acid synthesis
1. Synthesis of cytoplasmic acetyl CoA (transfer of mitochondrial acetyl CoA to cytoplasm via citrate shuttle)
2. Acetyl CoA carboxylation to malonyl CoA (via acetyl CoA carboxylase with biotin) [+ insulin, citrate]
3. Assembly of palmitate (via fatty acid synthase and Vit B5)
3474
Steps in palmitate assembly
1. Condensation
2. Reduction
3. Dehydration
4. Reduction
3475
What is the fate of Palmitate after its production?
1. Further elongation in SER and mitochondria
| 2. Desaturated in the ER (but not past the 9th carbon)
3476
Main storage form of fatty acids
Triacylglycerols
3477
Where does TAG synthesis occur?
Liver and adipose tissue
3478
Sources of glycerol-3-phosphate
1. DHAP from glycolysis (liver and adipose)
| 2. Phosphorylation of free glycerol (liver)
3479
What enzyme is responsible for the release of free fatty acids from TAGs?
Hormone sensitive lipases
3480
In the bloodstream fatty acids are always bound to?
Albumin
3481
Hormone sensitive lipases can only release what free fatty acids stored in TAG?
C1 & 3 thus resulting in
TAG -> 2 free FA and 2-mono acyl glycerol
3482
Where does B-oxidation of fatty acids occur
Mitochondria of all cells, but the fatty acid activation raft occurs in the Cytosol
Exception: RBC, kidney medulla, neurons, testes
3483
Rate limiting step in B-oxidation
Fatty acyl CoA + carnitine -> fatty acyl carnitine + CoA
| Enzyme: carnitine acyl transferase I
3484
Cutoff number of carbons that do not need a shuttle
Less than 12 carbons
3485
Steps in the carnitine shuttle
1. Fatty acyl synthase activates the fatty acid
2. Carnitine acyl transferase 1 attaches to fatty acyl to carnitine in the outer mitochondrial membrane
3. Fatty acyl-carnitine is shuttle through the inner membrane
4. Carnitine acyl transferase-2 transfers fatty acyl group back to a CoA in the mitochondrial matrix
3486
Steps in beta oxidation
1. Oxidation
2. Hydratiion
3. Oxidation
4. Thiolysis
3487
Beta oxidation of fatty acids with an odd number of carbon atoms releases?
Propionyl CoA which is converted to methylmalonyl coa (requires B12) then to succinyl CoA
3488
Which is responsible for the conversion of very long chain fatty acids?
Peroxisomes but if unsaturated it requires 3,2 enol-CoA isomerase
3489
Energy yield in ATP of beta oxidation of palmitate
129 ATP
7 NADH= 21
7 FAD= 14
8 acetyl CoA= 96
Activation = -2
3490
Intake of this compound depletes the body's NAD+ supply leading to accumulation Of fat in the liver
Alcohol
3491
Type of carnitine deficiency which leads to impaired FA oxidation and ketogenesis with hypoglycemia?
CPT-1 deficiency
3492
Type of carnitine deficiency which affects skeletal muscle and when severe the liver
CPT-2 deficiency
3493
It is a disorder school results in decreased fatty acid oxidation. Without the ATP to support gluconeogenesis, hypoglycemia becomes profound which may eventually leads to SIDS. It is prevented by frequent feeding with high carbohydrate and low fat diet.
Medium-chain fatty acyl-CoA dehydrogenase (MCAD) deficiency
3494
Associated with eating unripe fruit of the akee tree which contains hypoglycin thus activating MC and SC acyl CoA dehydrogenase
Jamaican vomiting sickness
3495
Rare neurological disorder which results to the accumulation of phytanic acid found in plant food stuff which blocks Boxidation
Refsum disease
3496
Cerebrohepatorenal syndrome resulting from the absence of peroxisomes in all tissues, it is characterized by liver dysfunction, jaundice, MR, weakness, hypotonia, and craniofacial dimorphism
Zellweger syndrome
3497
Defect in peroxismal activation of VLCFA thus leading to its accumulation. Ssx: apathy, behavral change, then visual loss spasticity, ataxia. All due to the fact since VLCFA are found in myelin tissue.
X-lied adrenoleukodystrophy
3498
Where does ketogenesis occur?
Liver mitochondria
3499
Products of ketogenesis
Acetoacetate and B-hydroxybutyrate (fuel)
| Acetone (cannot be used as fuel)
3500
Rate limiting step of ketogenesis
Acetoacetyl CoA + acetyl CoA --(HMG CoA synthase)--> HMG CoA
3501
What are the initial products that lead to the formation of acetyl CoA in ketogenolysis?
B-hydroxybutyrate -> acetoacetate -> acetyl coa
3502
What peripheral tissues can oxidize ketone bodes?
Those with mitochondria like the renal cortex, brain, and skeletal muscle
3503
Why cant liver convert acetoacetate to acetyl CoA?
It lacks succinyl-CoA acetoacetyl-CoA reductase (thiophorase)
3504
What is the Urine test for ketones? What ketone type does not it detect?
Nitroprusside test
Does not detect b-hydroxybutyrate
3505
Which part of cholesterol can a fatty acid attach to form a cholesteryl ester?
Single hydroxyl group of carbon 3 of the alpha ring
3506
Where does cholesterol synthesis occur?
All cells in the Cytosol and SER majority of which are found in the liver and intestines
3507
Substrates of cholesterol synthesis
Acetyl CoA, NADPH, ATP
3508
Rate limiting step in cholesterol synthesis
HMG CoA --(HMG CoA reductase)--> mevalonate
3509
Steps in Cholestid synthesis
1. Biosynthesis of mevalonate
2. Formation of isoprenoid units
3. Isoprene unit is formed from 6 isoprenoid units
4. Formation of lanosterol
5. Formation of cholesterol
3510
How is the cholesterol ring eliminated?
Through conversion to bile salts then secretion to bile
3511
Bile acid synthesis, found in the liver and Cytosol, rate limiting enzyme is?
Cholesterol-7-a-hydroxylase
3512
What are the primary bile acids?
Cholic acid
| Chenocholic acid
3513
What are the two amino acids used in bile acid conjugation to form bile salts?
Taurine and glycine
3514
What are the secondary bile acids?
Deoxycholic acid
| Lithocholic acid
3515
Where does steroid hormone synthesis occur?
SER of the adrenal glands, ovaries and testes, and placenta
3516
What is blocked by the drug aminogluthetimide?
The conversion of cholesterol to pregnenolone by desmolase
3517
The enzyme responsible for the breakdown of TAG to FA and:
A) 2-MAG from diet
B) FREE glycerol from chylomicrons and VLDL
C) 2-MAG from adipose
A) pancreatic lipase
B) Lipoprotein lipase
C) hormone sensitive lipase
3518
Lipoprotein with the largest percentage of TG
Chylomicrons
3519
Lipoprotein with the largest percentage of cholesteryl esters
LDL
3520
Chylomicrons transport TG and cholesterol from where to where?
Intestines to tissues
3521
VLDL transports TG from where to where?
Liver to tissues
3522
What apoprotein activates lipoprotein lipase?
APO-CII
3523
What apolipoprotein uptakes remnants by the liver?
APO E
3524
Apolipoprotein B-48 is used by chylomicrons which are created by the?
Epithelial cells
3525
What apolipoprotein is secreted by the liver for VDL?
B-100
3526
How does IDL become LDL?
By picking up cholesterol from HD!
3527
Which apoprotein delivers cholesterol into cells?
LDL
3528
Which apolipoprotein is used by HDL to activate lecithin cholesterol acyl transferase or LCAT to produce cholesterol esters?
APO-A1
3529
Difference between Type II familial hypercholesterolemia and type IV familial hypertriglyceredemia?
The former has high LDL leader to xanthomas and xanthelasmas with increased risk of atherosclerosis and CHD
The latter has increased VLDL production leading to a triad of
1. DM type 2
2. CAD
3. Obesity
3530
Phospholipid is composed of
DAG
Alcohol
Phosphodiester bond
3531
Most abundant phospholipid which is important in nervous transmission
Phosphatidylcholine
3532
Phospholipid playing a role in apoptosis
Phosphatidyl serine
3533
Phospholipid that is a major component of surfactant?
Dipalmitoylphosphatidylcholine
3534
Phospholipid reservoir for arachidonic acid in the membranes
Phosphatidylinositol
3535
What phospholipid is essential in mitochondrial function which is also used as a non-troponemal test due to its ability to act as an antigen?
Cardiolipin
3536
```
Composition of these glycolipids:
Ceramide
Cerebroside
Globoside
Ganglioside
Sulfatide
```
Ceramide: sphingosine + FA
```
Ceramide + ________
Glucose or galactose = Cerebroside
Oligosacchardide = Globoside
N-acetylneuramic acid = Ganglioside
Sulfated galactose = Sulfatide
```
3537
Hexosaminidase a ficiency leading to Ssx like cherry red macula, MR, hypotonia
Tay-Sachs disease
3538
A-galactosidase deficiency leading to 3Rs: recessive x-linked, rash, renal failure
Fabrys disease
3539
B-glucosidase deficiency leading to hepatosplenomegaly and erosion of long bones
Gauchers dissease
3540
Sphingomyelinase deficiency leading to hepatosplenomegaly
Nieman-pick disease
3541
The set of all proteins expressed by an individual at a particular time
Proteome
3542
Aims to identify the entire complement of proteins elaborated by a cell under diverse conditions
Proteomics
3543
What amino acid is needed to form ALA in heme synthesis?
Glycine combined with succinyl CoA
3544
Which amino acid carries nitrogen from the liver?
Alanine
3545
Which amino acids are implicated in maple syrup disease
valine, lucine, isoleucine
3546
What enzyme is responsible for the buildup of phenyl lactate, phenyl acetate, and phenylpyruvate?
Phenylalanine hydroxylase
3547
What amino acid is the precursor for niacin, serotonin, and melatonin?
Serotonin
3548
What is the amino acid precursor for homocysteine?
Methionine
3549
What amino acid contributes to the fibrous structure of collagen and interrupts a-helices in globular proteins?
Proline
3550
Increase of the combination of this Amino acid is responsible for the curly hair of people?
Cysteine + cysteine = cystine
3551
Amino acids with sites for O-linked glycosylation in the Golgi apparatus?
Serine and threonine
3552
Site for n-linked glycosylation in the ER
Asparagine
3553
Amino acid deaminated by an enzyme which results in the formation of ammonia. This is the major carrier of nitrogen to the liver from peripheral tissues,
Glutaminase deaminates glutamine
3554
Amino acid used in the determination for Folic acid deficiency. What is the test called?
Histidine used in the N-forminoglutamate excretion test
| Increased amounts of FIGu in urine by Folic acid deficient individuals after histindine intake
3555
Precursor amino acid for creatinine, urea, nitric oxide
Arginine
3556
Essential amino acids that cannot be synthesized by the body and must come from the diet
PVT TIM HALL always ARGues and never TYRes
Phenylalanine, valine, tryptophan, threonine' isoleucine, methionine, histidine, argenine, Leucine, Lysine
3557
Heme is a complex of?
Protoporphorin IX and heme
3558
What is the Bohr effect?
HBO2 + H+ HbH + O2
3559
What is an oxidized for of HB (Fe 3+) that does not bind O2 readily which could lead to chocolate cyanosis ? It is treated with oral methylene blue or ascorbic acid up to IV methylene blue.
Methemoglobin
3560
Hemoglobin bound to carbon monoxide instead of O2 leading to a cherry pink color.
Carboxyhemoglobin
3561
HB bound to carbon dioxide is called
Carbaminohenoglobin
3562
Classification of alpha and beta thalassemia
Alpha: silent carrier, a-thalassemia trait, Hb H disease, hydrops fetalis
Beta: B-thalassemia minor and major
3563
Most frequently affected collagen in Ehler Danlos syndrome leading to hyper extensible skin, tendency to bleed, hyper mobile joints, and increased risk for berry aneurysms.
Collagen type 3
3564
Collagen I mutation leading to bendable and easily fractured bones. Accompanied with blue sclerae, hearing loss, and dental imperfections.
Osteogenesis imperfecta
3565
Vitamin C deficiency leading to decreased hydroxylation of collagen. This leads to sore spongy gums, loose teeth, poor wound healing, and petecchiae on skin and mucous membranes.
Scurvy
3566
Type IV collagen defect leading to hematuria and ESRD
Alpert syndrome
3567
Collagen defect leading to kinky hair due to a deficiency of copper required by lysyl oxidase to strengthen collagen fibers.
Menke syndrome
3568
Skin breaking and blisters as a result for minor trauma. This disease is due to a defect in collage VII.
Epidermolysis bullosa
3569
Like collagen elastin has pro line and Lysine but has little and no?
Hydroxyproline
| Hydroxylysine
3570
Protein degradation mechanisms of nitrogen
Energy dependent ubiquitin-proteosome mechanism
| Non-energy dependent degradation enzyme
3571
Phases in amino acid catabolism
First phase: removal of a-amino group forming ammonia and a corresponding ketoacid
Second phase: carbon skeletons of a-ketoacids are converted to common intermediates of energy producing metabolic pathwas
3572
Two main steps in nitrogen removal from AA
1. Transamination
| 2. Oxidative deamination
3573
Where does transamination occur?
All cells of the body
3574
All but two amino acids transfer their amino groups to a-ketoglutarate except?
Lysine and threonine
3575
What is the coenzyme for the two aminotransferases?
Pyridoxal phosphate (vitamin B6)
3576
Oxidative deamination occurs where and for which amino acid only?
Liver and kidney
| Only glutamate
3577
Glutamate is oxidized by glutamate dehydrogenases and deaminated to form ?
free ammonia which is used to make urea
3578
What does the conversion of glutamate to a-ketoglutarate yield? What about vice versa?
Glutamate -> a ketoglutarate NH3 + NADH
| A ketoglutarate -> glutamate NADP+ + NH3
3579
How is excess nitrogen removal from peripheral tissues removed?
1. Glutamine: via glutamate + ammonia (through Flutamide synthaetase)
2. Alanine: via glucose -> pyruvate + glutamate -> alanine cycle
3580
Glutaminase deaminates glutamine to produce ammonium ion which is excreted from the body. Where are the two tissues this enzyme could be located?
Kidneys and small intestines
3581
Another name for urea cycle
Ornithine cycle or krebs-henseleit cycle
3582
What are the donors of the urea molecule?
1. NH3 from free ammonia
2. NH3 from aspartate
3. 1C and 1O from CO2
3583
Reactions in the urea cycle
1. Formation of carbamoyl phosphate (via carbamoyl phosphate synthetase I)
2. Formation of citrulline (via Ornithine transcarbamoylase)
3. Synthesis of arginosuccinate (arginosuccinate synthetase)
4. Cleavage of arginosuccinate to form arginine (Arginosuccinase)
5. Arginine cleavage to yield urea and Ornithine (arginase)
3584
Rate limiting step of urea cycle
Carbamoyl phosphate synthetase I
3585
Energy requirement of urea cycle
4 ATP
3586
Co factors of urea cycle
N-acetylglutamate
| Biotin
3587
Hereditary hyperammonemia produces symptoms such as
Hyperammonemia, elevated blood glutamine, decreased BUN
| Parents with lethargy, vomiting, hyperventilation, convulsions, cerebral edema, coma, and death
3588
Treatment for hereditary hyperammonemia
Low protein diet
| Administration of sodium benzoate or phenylpyruvate to capture and excrete excess nitrogen
3589
Ketogenic carbon skeletons of AA
Leucine
Lysine
Yields acetoacetate or acetyl-coa/ acetoacetyl-coa
3590
Ketogenic and glucogenic carbon skeletons of AA
```
WIFY
Phenylalanine
Isoleucine
Tryptophan
Tyrosine
```
Yields Ketogenic and glucose or glycogen by products
3591
This amino acid acts as a raw material in the biosynthesis of Heme, purines, creatine
Glycine
3592
This amino acid acts as a raw material in the biosynthesis of phospholipid, sphingolipid, purines, thymine
Serine
3593
This amino acid acts as a raw material in the biosynthesis of GABA
Glutamate
3594
This amino acid acts as a raw material in the biosynthesis of creatine, polyamines, nitric oxide
Arginine
3595
This amino acid acts as a raw material in the biosynthesis of serotonin, NAD+, NADP+, melatonin
Tryptophan
3596
This amino acid acts as a raw material in the biosynthesis of catecholamines, thyroid hormones, melanin
Tyrosine
3597
3 hormones dependent on tyrosine
Thyroid hormones
Melanin
Catecholamines
3598
Deficiency of homogenistic acid oxidase in the degrative pathway of tyrosine which results in urine turning to black on standing with dark connective tissues (ochronosis)
Alkaptonuria
3599
Congenital deficiency due tyrosinase deficieny or defective tyrosine transporters which leads to an increased risk for skin cancer.
Albinism
3600
Autosomal recessive disorder that may either be due to decreased methionine, increased cysteine, B6, and folate or decreased affinity for cystathione synthase. This results in mental retardation, osteoporosis, tall stature, lens subluxation, and atherosclerosis.
Homocystinuria
3601
Common inherited defect of renal tubular amino acid transporter for its parent compound, Ornithine, Lysine, and arginine, in the PCT of the kidneys. It eventually precipitates and cause staghorn caliculi. What is its treatment?
Cystinuria is treated with acetazolamide to alkalinize the urine
3602
The initial and last three steps of heme synthesis occurs in?
The mitochondria
3603
Heme synthesis summary
1. Formation of ALA (via ALA synthase and B6)
2. Formation of porphobilinogen
3. Formation of uroporphyrinogen
4. Formation of heme
3604
Lead inhibits what two steps in heme synthesis?
1. Introduction of Fe 2+ into protoporphyrin IX via ferrochelatase
2. Condensation of two ALA molecules by zinc containing ALA dehydratase
3605
Where is B6 a cofactors of?
1. Heme synthesis
2. Synthesis of cystathionine from homocysteine
3. Transamination between alanine and a-ketoglutarate
3606
Most common porphyria
Porphyria cutanea tarda
3607
Which part of heme synthesis do these symptoms appear?
1. Photosensitivity
2. Neuropsychiatric symptoms
1. After ring formation
| 2. Before ring formation
3608
Pyridoxine ficiency associated with isoniazid therapy results in this histopathologic finding
Sideroblastic anemia with ringed sideroblast
3609
Poisoning due to this heavy metal leads to coar basophilic stippling of RBC, peripheral neuropathy, lines in gums, increas in urinary ALA and free erythrocytes porphorin
lead poisoning
3610
Microcytic hypo chromic anemia is found in
IDA
Thalassemia
Lead poisoning
3611
Megaloblastic anemia is found in
Folate or B12 deficiency
| Pernicious anemia
3612
Normoyctic normochromic anemia is found in
Anemia of chronic kidney disease
| Blood loss
3613
Increase in MCHC is found in
Hereditary spherocytosis
3614
Summary of heme degradation
1. Formation of bilirubin
2. Uptake of bilirubin by the liver
3. Formation of bilirubin diglucoronide
4. Secretion of bilirubin into bile
5. Formation of urobilins in the intestine
3615
Colors of biliverdin, bilirubin, urobilinogen, stercolin, urobilin
```
Biliverdin: green
Bilirubin: red orange
Urobilinogen: colorless
Stercolin: brown orange red
Urobilin: yellow
```
3616
Examples of unconjugated hyperbilirubinemia
```
Hemolytic anemia
Physiologic jaundice
Crigler-najjar syndrome types I and II
Gilbert syndrome
Toxic hyperbilirubinemia
```
3617
Examples of conjugated hyperbilirubinemia
Biliary tree obstruction
Dubin-Johnson syndrome
Rotor syndrome
3618
What reaction measures total and direct bilirubin?
Van den bergs reaction
