Biochem 3 Flashcards
(165 cards)
1
Q
Kwashiorkor
A
Protein malnutrition! Skin lesions, edema, liver malfunction (fatty change due to dec. apolipoprotein synthesis). Small child with swollen belly.
2
Q
Kwashiorkor mnemonic
A
MEAL: Malnutrition (protein), Edema, Anemia, Liver (fatty)
3
Q
Marasmus
A
Total calorie malnutrition resulting in tissue and muscle wasting, loss of SubQ fat, and variable edema
4
Q
How much net ATP via malate-aspartate shuttle
A
- because NADH is used in cytosol and matrix so you don’t lose anything.
5
Q
Net ATP via glycerol-3-phosphate shuttle
A
- because you end up with reduced FADH2, so you end up losing 2 ATP per glucose (2.5(NADH)-1.5(FADH2)=1 (the loss of energy from one pyruvate formed)
6
Q
Malate-aspartate shuttle
A
Needed because NADH can’t cross the inner mitochondrial membrane. In cytosol OAA is converted to malate and this then enters matrix to produce a new NADH in the TCA cycle. Aspartate is the way OAA can move from matrix to cytosol.
7
Q
Glycerol-3-phosphate shuttle
A
DHAP formed in glycolysis is reduced to glycerol-3-phosphate which is then oxidized by glycerol-3-phosphate dehydrogenase which gives its electrons to FADH2, hence the loss. It also is a way of regenerating NAD+ for glycolysis.
8
Q
Glycolysis net ATP production
A
2 net
9
Q
Arsenic effect
A
Causes glycolysis to produce 0 net ATP
10
Q
What does CoA and lipoamide carry
A
Acyl groups
11
Q
What does Biotin carry
A
COOH (carboxylic acid group)
12
Q
What does THFs carry
A
1-carbon units
13
Q
What does SAM carry
A
Methyl (CH3) groups
14
Q
What does TPP carry
A
Aldehydes
15
Q
What family of molecules in NAD+ and NADP+
A
Nicotinamides from vitamin B3 (Niacin)
16
Q
What family is FAD+
A
Flavins (Riboflavin B2)
17
Q
NAD+ for what general reactions
A
Catabolic (for energy production)
18
Q
NADPH+ for what general reactions
A
Anabolic processes (steroid and fatty acid synthesis), Respiratory burst,
Cytochrome P-450 system
Glutathione reductase
19
Q
First step of glycogen synthesis in the liver?
A
Glucose to glucose-6-phosphate
20
Q
Know all the differences between Hexokinase vs. Glucokinase…
A
Location, Km, Vmax, Induced by Insulin, Feedback-inhibited by glucose-6-P, gene mutation associated with maturity onset diabetes of the young (MODY)
21
Q
What does it mean that hexokinase is feedback-inhibited by glucose6P
A
Excess glucose-6-P will stop hexokinase which makes sense in muscles where you only use the pathways to make energy. In liver, you’ll have excess glucose-6-P but you don’t want to slow it down so it does not feedback-inhibit.
22
Q
What is MODY
A
Aut. dom. gene disrupting insulin production. (monogenic diabetes) Type I and Type II are multigenic
23
Q
What does phosphofructosekinase-1 reaction do
A
Fructose-6-P to Fructose-1,6-bisphosphate
24
Q
What reactions in glycolysis produce ATP?
A
1,3-BPG to 3-PG by phosphoglycerate kinase AND
Phosphoenolpyruvate to pyruvate by Pyruvate Kinase
25
Why does fructose-2,6-BP induce PFK-1?
Because when glucose is in high supply it is produced by PFK-2 and activates PFK-1
26
Why does alanine slow down pyruvate kinase?
alanine is made from pyruvate so if you have too much alanine, you probably have a lot of pyruvate, hence pyruvate kinase not needed.
27
Know regulation by F2,6BP
.....
28
Are Fructose bisphosphatase-1 and PFK-1 the same enzyme with different phosphorylations too?
No. They are not the same. PFK-1 reaction is unidirectional.
29
Where is pyruvate dehydrogenase complex and what does it do?
it is mitochondrial and links glycolysis to TCA cycle
30
When is PDH active?
In fed state
31
PDH has how many enzymes
3
32
Name the PDH cofactors
1. Pyrophosphate (B1, thiamine; TPP)
2. FAD (B2, riboflavin)
3. NAD (B3, niacin)
4. CoA (B5, pantothenate)
5. Lipoic acid
33
What activates PDH
Exercise which also increases Ca2+, ADP, and NAD+/NADH ratio which all increase PDH
34
What is the basic reaction for PDF
pyruvate+NAD+ +CoA leads to acetyl-CoA+CO2+NADH
35
PDH is like what TCA cycle complex
alpha-ketoglutarate dehydrogenase complex (same cofactors, simlar substrate and action)
36
Arsenic does what to PDH
Inhibits lipoic acid
37
Arsenic presentation
Vomiting, rice-water stools, garlic breath
38
What happens if PDH is deficient
Buildup of pyruvate that shunts to form lactate (via LDH) and alanine (via ALT)
39
PDH def. findings
neurologic defects, lactic acidosis, increased serum alanine starting in infancy
40
PDH def. tx
Increased intake of ketogenic nutrients (e.g. high fat content or inc. lysine and leucine)
41
Lysine and Leucine are what...
The only purely ketogenic amino acids
42
Write out the pathways for pyruvate metabolism.
.....
43
Lactic acid dehydrogenase is used where
Major pathway in RBCs, leukocytes, kidney medulla, lens, testes and cornea
44
Mnemonic for TCA
Citrate Is Kreb's Starting Substrate For Making Oxaloacetate
45
Write out steps for TCA
.....
46
Know the balanced equation for TCA cycle
1 Acetyl-CoA creates 3 NADH (7.5 ATP) + 1 FADH2 (1.5 ATP) + 1 GTP = 10 ATP....x2 equals 10
47
Where does FADH2 deposit it's electrons
At succinate dehydrogenase which is complex II, it does not pump protons
48
What does CoQ do?
Shuttles electrons from Complex I and II to Complex III
49
What does cytochrome C do?
Shuttle electrons from complex III to IV
50
Rotenone
Stops Complex I
51
Antimycin A
Stops Complex III
52
Cyanide, CO
Stops Complex IV
53
Oligomycin
Stops Complex V
54
Final electron acceptor?
Complex IV: combines O2 + H2 to produce H2O with the elctrons
55
2,4-Dinitrophenol
Destroys proton gradient by making membrane more permeable
56
Where are the protons pumped into?
Into the intermembrane space of the mitochondria
57
Where does electron transport chain occur??
Inner mitochondrial membrane
58
What side is ATP formed on?
Inside the mitochondrial matrix, protons leak through ATP synthase into the matrix
59
Where does TCA cycle take place
In the mitochondrial matrix
60
What are examples of uncoupling agents
2,4-dinitrophenol (weight loss), aspirin, thermogenin in brown fat
61
What is the effect of uncoupling agents?
Increase O2 consumption, ATP production stops, but electron transport continues and makes heat
62
Why can't muscle contribute to GNG?
No glucose-6-phosphatase
63
What are the irreversible enzymes of GNG?
1. Pyruvate carboxylase (pyruvate + biotin (CO2) and ATP to produce OAA) in Mitochondria
2. Phosphoenolpyruvate carboxykinase (OAA to phosphoenolpyruvate via GTP) in cytosol
3. Fructose-1,6-bisphosphatase (Frcutose1,6BP to fructose6P) in cytosol
4. Glucose6P to glucose in ER
64
Where can you find GNG enzymes?
Mostly liver, but also kidney, intestinal epithelium
65
How do fatty acids contribute to the metabolic pathways
Odd-chain fatty acids yield propionyl-CoA (3 C remnant of fatty acid) which can go into succinyl CoA and go into GNG. Even-chain fatty acids yield acetyl-CoA equivalents, cannot be used in GNG.
66
HMP stands for
Hexose Monophosphate, also known as the pentose phosphate pathway
67
HMP shunt contributes to
Glutathione reduction, ribose production, glycolytic intermediates
68
HMP shunt uses how much ATP
No ATP is used
69
Where does HMP shunt take place
lactating mammary glands, liver, adrenal cortex (sites of fatty acid or steroid synthesis), RBCs
70
What is the oxidative step of HMP shunt?
Irreversible. Glucose-6-P forms Ribulose-5-P with the production of 2 NADPH and 1 CO2. This is via Glucose-6-P dehydrogenase and is the rate limiting step.
71
What is the nonoxidative step of HMP shunt?
Ribulose-5-P forms Ribose-5-P, Glyceraldehyde3P, and fructose-6-P. It requires B1 (thiamine. The enzymes are phosphopentose isomerase, transketolases
72
Explain respiratory burst...
NADPH is in phagolysosomes which reduce O2 to form superoxide which then can form H2O2 via superoxide dismutase. The H2O2 combines with chloride to form HOCL-, hypocholrite ion (bleach) to destroy the bacterium....
73
What is myeloperoxidase
Blue-green heme-containing pigment that gives sputum its color
74
What makes superoxide
NADPH oxidase
75
What makes H2O2
Superoxide dismutase
76
What makes HOCl
Myeloperoxidase
77
Explain the glutathione cycling steps
Glutathione peroxidase oxidizes it to reduce the free radical, gluathione reductase with NADPH reduces it to GSH
78
How is H2O2 broken down...
In bacteria, catalase
| In humans, by glutathione peroxidase (glutathione is oxidized, reducing H2O2 to H2O)
79
What is pyocyanin
From P. aeruginosa that generates ROS to kill competing microbes
80
What is lactoferrin
Protein in secretory fluids and PMNs that inhibits microbial growth via iron chelation
81
Chronic granulomatous disease patients are at increased infection from what
Catalase + species (they can't use the bacteria's H2O2 because the bacteria break their own down)
82
is the breakdown of H2O2 oxidation or reduction?
H2O2 is reduced to H2O
83
What are some oxidizing agents in G6PD deficiency
Fava beans, sulfonamides, primaquine, antituberculosis agents. INFECTION: free radicals from inflammatory response
84
G6PD def. is due to what
Can't produce enough NADPH
85
G6PD def. genetics, ethnicity, benefits
X-linked recessive, most common human enzyme deficiency, more prevalent among blacks. Increased malarial ressitance.
86
Pathology of G6PD def.
BITE into some HEINZ ketchup
87
What is the end product of G6PD?
6-phosphogluconate
88
Essential fructosuria
Defect in fructokinase. Benign, asymptomatic condition since fructose is not trapped in cells.
89
Ess. fructosuria Genetics and presentation
Aut. rec.
| Asymptomatic, but fructose in blood and urine
90
Fructose or galactose disorders are worse?
Galactose disorders are worse for the analogous conditions
91
Fructose intolerance genetics and path
Aut. rec. deficiency of Aldolase B. Fructose-1-P accumulates, sequestering pshophate, which inhibits glycogenolysis and GNG.
92
Fructose intolerance presentation
After consuming fruit, juice, or honey. Hypoglycemia, jaundice, cirrhosis, and vomiting.
93
Fructose intolerance lab work
Urine dip negative (glucose tested only); reducing sugar in urine positive (nonspecific)
94
Fructose intolerance tx
Decrease fructose and sucrose intake
95
how does fructose bypass PFK
by triose kinase which turns glyceraldehyde into glyceraldehyde-3-P which can then enter glycolysis
96
Galactokinase deficiency genetics and path
Aut. rec. deficiency of galactokinase. Galactitol accumulates if galactose is present in diet.
97
Galactokinase deficiency presentation
Relatively mild. Galactose in bloond and urine. Infantile cataracts. Failure to track objects or develop a social smile.
98
Classic galactosemia genetics and path
Aut. rec. absence of galactose-1-phosphate uridyltransferase. Accumulation of toxic substances (including galactitol (accumulates in eye))
99
Classic galactosemia presentation
failure to thrive, juandice, hepatomegaly, infantile cataracts, intellectual disability
100
Classic galactosemia tx
exclude galactose and lactose from diet
101
Mnemonic for galactose and fructose metabolism problems
FAB GUT
| Fructose is to Aldolase B as Galactose is to Uridyl-Transferase
102
Classic galactosemia and neonate condition
E. coli sepsis in neonates
103
What causes the serious defects of fructose and galactose metabolism (general mechanism)
Depletion of phosphate
104
sorbitol metabolism
it is the sugar alcohol of glucose made by Aldose reductase (uses NADPH), can be turned to Sorbitol Dehydrogenase using up a NAD+
105
Too much sorbitol??
From chronic hyperglycemia: can cause cataracts, retinopathy, and peripheral neuropathy
106
What creates sugar alcohols
Aldose reductase (with NADPH)
107
What cells have both aldose reductase and sorbitol dehydrogenase
Liver, ovaries, and seminal vesicles
108
What cells have only aldose reductase
Scwann cells, retina, and kidneys. lens has primarily aldose reductase
109
Causes of lactase deficiency
Primary: age-dependent decline after childhood (absence of lactase-persistent allele), common in Asians, Blacks, and Native Americans.
Secondary: Loss of brush border due to gastroenteritis (e.g. rotavirus), autoimmune disease
Congenital lactase deficiency: rare
110
Lactase deficiency lab tests
Low stool pH and positive hydrogen breath test with lactose tolerance test. Normal mucosa on biopsy with heriditary lactose intolerance.
111
Lactase deficiency presentation
Bloating, cramps, flatulence, osmotic diarrhea
112
Lactase def. tx
Avoid dairy products or add lactase pills to diet; lactose-free milk
113
Name the essential Amino Acids
Methionine, valine, histidine, isoleucine, phenylalanine, threonine, tryptophan, leucine, lysine (9 total)
114
What are the glucogenic amino acids
Methionine, valine, histidine
115
What are the glucogenic/ketogenic amino acids
isoleucine, phenyalanine, threonine, and tryptophan
116
What are the ketogenic amino acids
Leucine and Lysine
117
What are the acidic amino acids
Glutamic acid and aspartic acid (neg. at body pH)
118
What are the basic amino acids
Arginine, lysine, histidine
119
What is the most basic amino acid
Arginine
120
What basic amino acid has no charge at body pH
Histidine
121
What basic amino acids needed during periods of growth
Arginine and histidine
122
Know the steps of the urea cycle
....
123
What makes up each urea molecule
NH3, CO2, and aspartate
124
Explain how ammonia is transferred from muscle to liver
Amino acids give the amino group to alpha ketoglutarate forming alphaketoacids and glutamate. Glutamate gives its amino group to pyruvate to form alanine, alanine can then go to the liver, add its amino to alphaketoglutratae to form glutamate which participates in the urea cycle.
125
What is the cori cycle
It is how lactate is recycled from the muscle to the liver. From lactate to pyruvate to glucose and then pumped back out.
126
What is the path of hyperammonemia
Depletes alphaketoglutarate so TCA stops
127
Ammonia intoxication
tremor (asterixis), slurring of speech, somnolence, vomiting, cerebral edema, blurring of vision.
128
Treating hyperammonemia
Limit protein in diet. Benzoate or phenylbutyrate which bind amino acid and lead to excretion. Lactulose to acidify GI tract and trap NH4 for excretion
129
What happens if you have a deficiency of N-acetylgutamate
You get hyperammonemia because you can't use carbamoyl phosphate synthetase I
130
N-acetylglutamate deficiency presentation
Presentation identical to carbamoyl phosphate synthetase I deficiency.
131
N-acetylglutamate deficiency diagnosis
elevated ornithin with normal urea cycle enzymes suggets hereditary n-acetylglutamate deficiency
132
most common urea cycle disorder
ornithine transcarbamylase deficiency
133
OTC def. genetics and path
X linked rec. excess carbamoyl phospahte converted to orotic acid (part of pyrimidine synthesis pathway)
134
OTC def. presentation
Evidence in first few days of life, but may present with late onset.
135
OTC def. lab work
elevated orotic acid in blood and urine, low BUN, symptoms of hyperammonemia. No megaloblastic anemia (vs. orotic aciduria)
136
How to make histamine
From histidine with B6
137
How to make heme
From porphyrin which is made from glycine with B6
138
How is GABA made
From glutamate with B6
139
How is glutathione made
From Glutamate
140
Where does Creatine, urea, and nitric oxide come from
From arginine. NO uses BH4
141
Know the pathway of phenylalanine metabolism
.........
142
What does DOPA stand for
Dihydroxylphenylalanine
143
What is responsible for causing albinism
Defective tyrosinase which turns DOPA into melanin
144
What does carbidopa block
DOPA decarboxylase
145
What causes alkaptonuria
Defective homogentisate oxidase
146
Homogentisic acid comes from what
Tyrosine
147
Alkaptonuria genetics and path
Aut. rec. congenital deficiency of homogentisate oxidase in the degradative pathway of tyrosine to fumarate.
148
Alkaptonuria presentation
Benign disease. Dark connective tissue, brown pigmented sclerae, urine turns black on prolonged exposure to air. May have debilitating arthralgias. (homogentisic acid toxic to cartilage)
149
what is Cahill cycle also called
the alanine cycle
150
Why does lactic acid fermentation happen
To regenerate NAD+ to continue glycolysis because either 1. TCA has stopped because of anaerobic conditions or 2. Too much pyruvate for TCA or 3. Too much NADH
151
Glyceraldehyde-3-phosphate in heavy alcohol consumption goes through what process
Because of excess NADH, it turns to glycerol-3-phosphate and combines with fatty acids to make TGs and you get hepatosteatosis
152
Where does Pyruvate Dehydrogenase occur
Inside the mitochondrial matrix (pyruvate is actively shuttled into the matrix with a proton)
153
Know the basic pathway for GNG
Pyruvate to OAA via pyruvate carboxylase and moving with every normal enzyme of glycolysis backwards until you reach PFK-1 stage, where instead you use fructose-1,6-bisphosphatase and then use glucose-6-Phosphatase.
154
what does DHAP stand for
dihydroxyacetone phosphate
155
How many atoms in malonyl CoA vs. Acetoacetyl CoA
Malonyl CoA has 3 carbons but gives 2 to FA synthesis.
| AcetoacetylCoA also has 3 carbons, but lacks the carboxylic acid tail
156
Describe outer mitochondrial emmbrane
Has porins that allow for anything smaller than 5000 daltons to move through, hence it is essentially cytosol for all these molecules.
157
What is the permeability of the inner membrane
Freely permeable only to oxygen, carbon dioxide and water.
158
Difference between OAA and aspartate
Aspartate has an amino group on it via aspartate aminotransferase.
159
MODY presentation
Because it's aut. dom. 50% of first degree relatives have it. it presents in second to fifth decade.
160
What is LADA
latent autoimmune diabetes of adults (late Type I)
161
LADA presentation
Non-obese Type II person is typical.
162
Distinguish LADA from type II
Low C-peptide vs. high C-peptide. They have islet cell autoantibodies.
163
What is GSH vs. GSSG
When glutathione is oxidized, it forms a disulfide bond (GSSG), the reduced form is a sulfhydryl (GSH)
164
What is the basic explanation of GNG
Glycolysis has two irreversible reactions, pyruvate kinase and PFK-1, which are the only things that need a bypass in GNG. (you do this with OAA via PC and PEP carboxykinase)
165
Why can't citrate participate in GNG?
?????????
