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Flashcards in My Biochem Deck (3618):
0

Complex 1 inhibitors

Barbiturate
Amytal
Rotenone

Piercidin A

1

Complex II Inhibitors

Carboxin
TTFA
Malonate

2

Complex III Inhibitors

Antimycin A
Dimercaprol

3

Complex IV Inhibitors

Sodium azide
Hydrogen sulfide
Cyanide
Carbon monoxide

4

Complex v inhibitors

Oligomycin

5

Uncouplers

Aspirin
Dinitrophenol
Thermogenin

6

All complex mitochondrial disease

Fatal infantile mitochondrial myopathy

7

Complex I mitochondrial disease

MELAS (mitochondrial encephalomyopathy, lactic acidosis, stroke like episodes)

8

Complex II mitochondrial disease

Kearns-Sayre syndrome

9

Complex III mitochondrial disease

Leber's hereditary optic neuropathy

10

Complex IV mitochondrial disease

Leigh's disease
Ragged red muscle fiber disease

11

Glut transporter for erythrocytes

1

12

Glut transporter for brain

1 & 3

13

Glut transporter for kidney

1, 2, 3

14

Glut transporter for colon

1

15

Glut transporter for placenta

1 & 3

16

Glut transporter for liver

2

17

Glut transporter for pancreatic B cell

2

18

Glut transporter for small intestine

2, 5

19

Glut transporter for heart

4

20

Glut transporter for adipose

4

21

Glut transporter for skeletal muscle

4

22

Where does glycolysis occur?

Cytoplasm in all cells

23

What is the substrate for glycolysis?

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, elevate