Biochem Review Flashcards
1
Q
What is the rate-limiting enzyme in purine synthesis? Pyrimidine synthesis?
A
purine - glutamine PRPP amidotransferase
pyrimidine - CPS-2
2
Q
What are the sources of carbon in the synthesis of purines? In pyrimidine synthesis?
A
purines - CO2, glycine, THF (nitrogen source = aspartate and glutamine)
pyrimidines - aspartate and CO2 (nitrogens = glutamine)
3
Q
Which medication inhibits ribonucleotide reductase?
A
hydroxyurea
4
Q
Which medication inhibits dihydrofolate reductase?
A
methotrexate, trimethoprim
5
Q
Which medication inhibits thymidylate synthase?
A
5-FU
6
Q
Which medication inhibits inosine monophosphate dehydrogenase?
A
mycophenolate
7
Q
Which medication inhibits PRPP amidotransferase?
A
6-MP
8
Q
What accounts for the positive charge of histones? What accounts for the negative charge of DNA?
A
Lysine and arginine on histones
phosphate groups on DNA
9
Q
How many adenosine residues are found in a molecule of DNA if one strand contains A=2000, G=500, C=1500, T=1000?
A
3000 - 2000 A plus the 1000 from the other strand
10
Q
A boy with self-mutilating behavior, intellectual disability, and gout
A
Lesch-Nyhan
11
Q
Orotic acid in the urine elevated serum ammonia
A
ornithine-transcarbamoylase deficiency
12
Q
Orotic acid in the urine + normal serum ammonia
A
oratic aciduria
13
Q
Megaloblastic anemia that does not improve with folate and B12
A
oratic aciduria
14
Q
Lesch Nyhan syndrome
A
defective purine savage due to absent HGPRT (which converts hypoxanthine to IMP and guanine to GMP)
X-linked recessive
Sx = intellectual disability, self-mutilation, aggression, hyperuricemia (orange sand crystals in diaper), gout, dystonia
Tx = allopurinol, febuxostat
15
Q
oratic aciduria
A
inability to convert orotic acid to UMP because of defect in UMP synthase
Autosomal recessive
megaloblastic anemia refractory to folate and B12; no hyperammonemia (vs ornithine transcarbamylase deficiency)
Tx = uridine monophosphate to bypass mutated enzyme
16
Q
What strand of DNA nucleotides opposes this DNA strand: 5’-ATTGCGTA-3’?
A
5’-TACGCAAT-3’ (DNA is always written 5’->3’
17
Q
How does UV radiation damage DNA?
A
pyrimidine dimers on same strand of DNA (usually thymine-thymine, but can be cytosine-cytosine also)
18
Q
Which eukaryotic DNA polymerase replicates the lagging strand?
A
DNA polymerase alpha for the first 20 bases then DNA polymerase delta
19
Q
Which eukaryotic DNA polymerase synthesizes RNA primer?
A
DNA polymerase alpha
20
Q
Which eukaryotic DNA polymerase repairs DNA?
A
DNA polymerase beta
21
Q
Which eukaryotic DNA polymerase replicates mitochondrial DNA?
A
DNA polymerase gamma
22
Q
Which eukaryotic DNA polymerase replicates the leading strand of DNA?
A
DNA polymerase alpha for the first 20 bases, then DNA polymerase epsilon
23
Q
Nucleotide excision repair
A
DNA polymerase and ligase fill and reseal the gap, respectively; repairs bulky helix distorting lesions
24
Q
What disorder results from a problem in nucleotide excision repair?
A
xeroderma pigmentosum (very susceptible to damage from the sun)
25
Base excision repair
base-specific glycosylase removes altered base and creates AP site; AP endonuclease cleaves 5' end; lyase cleaves the 3' end; DNA polymerase beta fills the gap and DNA ligase seals it
26
Mismatch repair
mismatched nucleotides are removed, and the gap is filled and resealed
27
What disorder results from a defect in mismatch repair processes?
Lynch syndrome (hereditary nonpolyposis colorectal cancer)
28
Nonhomologous end joining
brings together two ends of DNA fragments to repair double-stranded breaks
29
What disorders result from defects in nonhomologous end joining?
ataxia telangiectasia
breast/ovarian cancers with BRCA1 mutation
Fanconi anemia
30
What is Bloom syndrome?
mutation of helices; affects both DNA replication and repair
Patients are hypersensitive to sunlight, have increased susceptibility to leukemias and lymphomas, immunodeficiency, infertility, and facial anomalies
31
What is a silent mutation?
nucleotide substation but codes for the same amino acid
32
What is a missense mutation? What is an example of this?
nucleotide substitution resulting in changed amino acid
| Ex = sickle cell disease (substation of glutamic acid with valine)
33
What is a nonsense mutation?
nucleotide substation resulting in early stop codon (UAG, UAA, UGA); usually results in a nonfunctional protein
34
What is a frameshift mutation? What is an example of this?
deletion or insertion of a number of nucleotides not divisible by 3, resulting in misreading of all nucleotides downstream
Ex = Duchenne muscular dystrophy, Tay-Sachs disease
35
What does helicase do?
unwinds template DNA at the replication fork
36
What do single-stranding binding proteins do?
prevents strands from reannealing
37
What does DNA topoisomerase do? What are the auto-Abs to it?
removes supercoils
| Auto Abs = anti-Scl-70 Abs found in diffuse scleroderma
38
What are the drugs that inhibit eukaryotic DNA topoisomerase? Prokaryotic?
eukaryotic - etoposide/teniposide
| prokaryotic - fluoroquinolones (also inhibit topoisomerase IV)
39
What elongates the lagging strand in prokaryotes?
DNA polymerase III
40
What elongates the leading strand in prokaryotes?
DNA polymerase III
41
What does DNA polymerase I do in prokaryotes?
degrades RNA primer; replaces it with DNA
42
What does DNA ligase do?
Joins Okazaki fragments
43
What amino acid is encoded by the most common start codon?
methionine
44
What is the difference between an intron and an extron?
introns get spliced out of the mRNA by the spliceosome
| externs go into the mature mRNA to be expressed
45
Production of what enzyme is regulated by the lac operon?
beta-galactosidase
46
What two proteins regulate the lac operon?
CAP and lac repressor
47
What two substrate conditions must be met for the lac genes to be transcribed?
1. presence of lactose in excess (moves repressor)
| 2. no glucose (CAP presence)
48
What are the different eukaryotic RNA polymerases?
RNA pol I -> rRNA
RNA pol II -> mRNA
RNA pol III -> tRNA
49
What is the difference between CPS1 and CPS2 enzymes? (location, pathway, nitrogen source)
location - CPS1 - mitochondria; CPS2 - cytosol
pathway - CPS1 - urea cycle; CPS2 - pyrimidine synthesis
nitrogen source - CPS1 - ammonia; CPS2 - glutamine
50
What is the first enzyme in the glycolysis pathway that catalyzes glucose/fructose -> what?
hexokinase or glucokinase catalyzes glucose/fructose -> glucose-6-phosphate
51
What enzyme catalyzes fructose-6-phosphate to fructose-1,6-bisphosphate in glycolysis?
phosphofructokinase-1
52
What stimulates phosphofructose-1?
AMP and fructose-2,6-bisphosphate
53
What inhibits phosphofructose-1?
ATP and citrate
54
What enzyme catalyzes the conversion of phosphoenolpyruvate to pyruvate in glycolysis?
pyruvate kinase
55
What stimulates the enzyme pyruvate kinase?
fructose-1,6-bisphosphate
56
What inhibits the enzyme pyruvate kinase?
ATP, alanine
57
What is the rate-limiting enzyme in glycolysis?
phosphofructokinase-1
58
What is the most commonly deficient enzyme in glycolytic enzyme deficiency? What are the symptoms?
most common cause: pyruvate kinase deficiency
| presentation: hemolytic anemia because RBC cannot make ATP without glycolysis; glycolysis is their sole source of ATP
59
A muscle biopsy on a patient of yours reveals elevated glycogen levels, elevated fructose-6-phosphate, and decreased pyruvate. What enzyme deficiency do you suspect most?
phosphofructokinase-1
60
What reaction does PFK-2 catalyze, and when is it active?
PFK2 catalyzes fructose-6-phosphate -> fructose-2,6-bisphosphate; active when insulin is present (fed state)
61
What reaction does FBPase-2 catalyze, and when is it active?
FBPase-2 catalyzes fructose-2,6-bisphosphate -> fructose-6-phosphate; active when glucagon in present (fasting) -> when you're fasting, you don't want to breakdown glucose; you want ht liver to make glucose, so you go through gluconeogenesis
62
What are the irreversible enzymes involved in glycolysis?
1. hexokinase/glucokinase
2. PFK-1
3. pyruvate kinase
63
What are the irreversible enzymes involved in gluconeogenesis?
1. pyruvate carboxylase
2. PEP carboxykinase
3. fructose-1,6-bisphosphatase
4. glucose-6-phosphatase
64
What enzyme catalyzes the rate-limiting step in gluconeogenesis?
fructose-1,6-bisphosphatase
65
Order the following molecules by how much energy they contain that can be made available to fuel endergonic reactions: pyruvate, adenosine monophosphate, glucose, adenosine, adenosine triphosphate
glucose, pyruvate, ATP, AMP, adenosine
66
What can be turned into pyruvate for the process of gluconeogensis?
1. odd chain FAs -> propionyl-CoA
2. TCA cycle molecules (oxaloacetate)
3. amino acids
67
What is the formula for Gibbs free energy?
delta G = delta H - T*deltaS
68
What is the enzyme that converts pyruvate into oxaloacetate in the first step of gluconeogenesis?
pyruvate carboxylase
69
What is required for the enzyme pyruvate carboxylase in gluconeogenesis? What stimulates this enzyme?
biotin is required; stimulated by acetyl-CoA
70
What enzyme turns oxaloacetate into PEP in the 2nd step of gluconeogenesis?
PEP carboxykinase
71
What enzyme catalyzes fructose-1,6-bisphosphate into fructose-6-phosphate?
fructose-1,6-bisphosphatase
72
What enzyme catalyzes glucose-6-phosphate into glucose or fructose in the last step of gluconeogenesis?
glucose-6-phosphatase
73
What is glycolysis?
glucose -> pyruvate
74
What is gluconeogensis?
pyruvate -> glucose
75
What is glycogenesis?
glucose -> glycogen
76
What is glycogenolysis?
glycogen -> glucose
77
What is the rate-limiting enzyme for glycogen synthesis?
glycogen synthase
78
What is the rate-limiting enzyme for glycogenolysis?
glycogen phosphorylase
79
Which enzyme converts glucose-6-phosphate to glucose in glycogenolysis?
glucose-6-phosphatase
80
Pompe Dz
deficiency of alpha-1,4-glucosidase in lysosomes
- Infantile form: severe muscle weakness, cardiomegaly, HF, die within 1 year
- Adult -> no cardiac problems, gradual onset of skeletal muscle weakness, diaphragm weakness -> respiratory failure
81
McArdle Dz
cannot breakdown glycogen due to glycogen phosphorylase deficiency -> rhabdomyolysis -> renal failure
82
Von Gierke Dz
glucose-6-phosphate deficiency (last step of glycogenolysis and gluconeogenesis); hypoglycemia with fasting, glycogen buildup in liver -> hepatomegaly, enlargement of kidneys, increased serum lactate, uric acid, and triglycerides
feed frequently and fed cornstarch at night
83
Cori Dz
alpha-1,6-glucosidase (debranching enzyme) deficiency (glycogenolysis); mild hypoglycemia
84
What four things can pyruvate be made into?
1. oxaloacetate
2. acetyl-coA
3. lactate (Cori cycle)
4. alanine
85
Why are alanine and glutamine found in such high concentrations in the blood?
they are two major carriers of nitrogen from tissues
86
What enzyme catalyzes transamination reactions?
transaminases transfer the amino group from an amino acid to alpha-ketoglutarate to form glutamine
87
What are the two most important transaminases? What do they catalyze?
1. alanine transaminase: catalyzes alanine + alpha-ketoglutarate -> glutamate + pyruvate
2. aspartate transaminase: catalyzes aspartate + alpha-ketolgutarate -> oxaloacetate + glutamate
88
What cofactor is required by all transaminases?
Pyridoxal phosphate (derivative of VitB6)
89
What are the major regulatory enzymes of the citric acid (TCA) cycle?
1. citrate synthase
2. isocitrate dehydrogenase
3. alpha-ketoglutarate dehydrogenase
90
What is the rate-limiting enzyme of the TCA cycle?
isocitrate dehydrogenase
91
What substances are known to inhibit the complexes of the electron transport chain?
1. complex 1 -> amytal (barbiturate) and rotenone (fish toxin)
2. complex 2 -> nothing
3. complex 3 -> antimycin A (fish toxin)
4. complex 4 -> CN-, CO, H2S, N3-
92
What substances can increase the permeability of the inner mitochondrial membrane, thereby decreasing ATP synthesis but increasing heat generation?
aspirin toxicity, 2,4-DNP, and thermogenin
93
In patients with G6PD deficiency, ingestion of what substances can induce oxidative damage to RBCs?
"Spleen Purges Nasty Inclusions From Damaged Cells"
- sulfonamides
- primaquine (anti-malarial)
- nitrofurantoin (UTIs)
- isoniazid (TB)
- fava beans
- dapsone (leprosy tx; PCP prophylaxis sometimes)
- chloroquine (malaria tx)
94
Essential fructosuria
deficient in fructokinase; autosomal recessive
| buildup of fructose -> spilled in urine (benign)
95
Fructose intolerance
deficient in aldolase B; autosomal recessive
increased fructose-1-phosphate
decreased phosphate -> inhibit glycogenolysis and gluconeogenesis
-hypoglycemia and vomiting
-hepatomegaly and jaundice
Tx - decreased intake of fructose and sucrose
96
Galactokinase deficiency
deficiency in galactokinase -> increased glactitol
| - infantile cataracts
97
Classic galactosemia
```
deficient in gal-1-P uridyltransferase
- worse cataracts than galactokinase def
- hepatomegaly and jaundice
- failure to thrive
- intellectual disability
Tx - lactose and galactose exclusion
```
98
Which tissues of the body use the pentose phosphate pathway?
RBCs, liver, adrenal cortex, mammary glands (during lactation)
99
Explain why a deficiency of the enzyme that is the rate limiter for the HMP shunt can result in hemolytic anemia
RBCs need NADPH to keep glutathione reduced to detoxify free radicals; so G6PD deficiency (rate-limiting enzyme) -> hemolytic anemia
100
What fuels are produced and used in the post absorptive period?
produced - glucose (from hepatic glycogenolysis and gluconeogenesis) and fatty acids (from adipose tissue)
used - muscles brain, and other tissues use predominantly glucose
101
When does gluconeogenesis begin int he post-absorptive period? When does it become fully active?
begins 4-6 hours after the last meal
| fully active when glycogen stores are depleted (10-18 hours after last meal)
102
How does the pattern of fuel production and usage change in early starvation (24 hours after the last meal)?
produced - glucose (gluconeogenesis) - used up glycogen stores; fatty acid being produced from adipose tissue
used - brain uses predominantly glucose; muscles and other tissues use some glucose but predominantly fatty acids
103
In intermediate starvation (48 hours after the last meal), how does the pattern of fuel production and utilization change?
produced - glucose, fatty acids, ketones (from liver)
used - brain uses predominantly glucose but also some ketone bodies; muscle and other tissues use predominantly fatty acids but also some ketone bodies
104
What are the main ketone bodies?
acetoacetate and beta-hydroxybutyrate
105
What is the rate-limiting enzyme in the synthesis of ketone bodies?
hmg-coA synthase
106
What metabolic scenario favors the synthesis of ketone bodies?
when production of acetyl-CoA from beta-oxidation fo fatty acids exceeds the oxidative capacity of the TCA cycle
107
Can ketone bodies be used by all body tissues?
No, RBCs can only use glucose
108
What is the pattern of fuel production and utilization in prolonged starvation (5 days after last meal)?
produced - glucose, fatty acids, ketone bodies
used - brain uses predominantly ketone bodies; muscles and other tissues use predominantly fatty acids but also some ketone bodies and glucose for RBCs
109
What percentage of energy comes from glucose and ketone bodies during an overnight fast? What about after a 3 day fast?
overnight fast - 90% of energy comes from glucose (2/3 from glycogen breakdown, 1/3 from gluconeogensis); 5% comes from ketone bodies
3 day fast - 60% of your energy comes from ketone bodies (1/2 acetoacetate, 1/2 beta-hydroxybutyrate); 40% from glucose (mostly gluconeogenesis)
110
What is the primary energy source in a patient that has not eaten in two days?
fatty acids
111
A stressed physician comes home from work, consumes seven or eight shots of tequila in rapid succession before dinner, and becomes hypoglycemia. Why did she become hypoglycemic?
liver is breaking down the ethanol, which generates a lot of NADH, which shunts pyruvate to production of lactate and oxaloacetate to production of malate; pyruvate and malate no longer available for gluconeogenesis
112
What are some of the hallmark features of kwashiorkor?
```
MEALS
M - malnourished
E - edema
A - anemia
L - liver (fatty)
S - skin/hair depigmentation
```
113
What does VLDL do?
delivers hepatic TGs to peripheral tissue
114
What do chylomicrons do?
deliver dietary TGs to peripheral tissues
115
What does IDL do?
formed in the degradation of VLDL; delivers TGs and cholesterol to liver
116
What does LDL do?
delivers hepatic cholesterol to peripheral tissues
117
What does HDL do?
mediates reverse cholesterol transport from periphery to liver
118
What is abetalipoproteinemia? mutation, deficiency, symptoms, tx?
autosomal recessive mutation in MTP gene
chylomicrons, VLDL, LDL absent
deficiency in ApoB48 and ApoB100
Infants present with fat malabsorption, steatorrhea, failure to thrive
Later Sx - retinitis pigments, spinocerebellar degeneration due to VitE def, progressive ataxia, acathocytosis, night blindness
Treatment: large doses of vitE
119
What deficiency causes familial hypercholesterolemia?
LDL receptors
120
Which apolipoprotein activates LCAT?
ApoA-1
121
Which apolipoprotein mediates chylomicron secretion?
ApoB-48
122
Which apoplipoprotein mediates VLDL secretion?
ApoB-100
123
Which apolipoprotein is a cofactor for lipoprotein lipase?
ApoC-11
124
Which apolipoprotein mediates uptake of remnant particles?
ApoE
125
What is the rate-limiting enzyme for fatty acid synthesis?
acetyl-CoA carboxylase
126
What is the rate-limiting enzyme for beta oxidation of fatty acids?
carnitine acyltransferase I
127
What is the rate-limiting enzyme for ketone body synthesis?
HMG-CoA synthase
128
What is the rate-limiting enzyme for cholesterol synthesis? Which drug class inhibits it?
HMG-CoA reductase; statins
129
What are the essential amino acids?
```
PVT TIM HaLL
phenylalanine
valine
threonine
tryptophan
isoleucine
methionine
histadine
leucine
lysine
```
130
What amino acid is a precursor to histamine?
histidine
131
What amino acid is a precursor to porphyrin/heme?
glycine
132
What amino acid is a precursor to nitric oxide?
arginine
133
What amino acid is a precursor to GABA?
glutamate
134
What amino acid is a precursor to S-adenosyl-methionine (SAM)?
methionine
135
What amino acid is a precursor to creatine?
arginine
136
What enzyme does carbidopa inhibit?
DOPA decarboxylase
137
PKU
autosomal recessive
due to decreased phenylalanine hydroxyls of decreased tetrahjydrobiopterin (BH4); tyrosine becomes essential
increased phenylalanine -> excess phenyl ketones in urine
Sx - intellectual disability, growth retardation, seizures, fair skin, eczema, musty body odor
Tx: decreased phenylalanine and increased tyrosine in diet; tetrahjydrobiopterin supplementation
138
Maple Syrup Urine Disease (MSUD)
autosomal recessive
Blocked degradation of branched amino acids (Isoleucine, Leucine, Valine) due to decreased branched-chain alpha-ketoacid dehydrogenase
Sx - severe CNS defects, intellectual disability, death
Tx - restriction of isoleucine, leucine, valine in diet & thiamine supplementation
(I Love Vermont maple syrup)
139
Alkaptonuria
autosomal recessive
congenital deficiency of homogentisate oxidase in the degradative pathway of tyrosine to fumarate -> pigment-forming homogentisic acid accumulates in tissue
Sx - bluish-black CT< ear cartilage, and sclera; urine turns black on prolonged exposure to air; may have debilitating arthralgias
Tx - add vita; avoid phenylalanine and tyrosine
140
Homocystinuria
```
autosomal recessive
cystathione synthase deficiency or methionine synthase deficiency
Sx - HOMOCYstinuria
increased homocysteine in urine
osteoporosis
marfanoid habitus
ocular changes
cardiovascular effects -> stroke and MI
kyphosis
intellectual disability
```
141
Cystinuria
autosomal recessive
hereditary defect of renal PCT and intestinal amino acid transporter that prevents reabsorption of COLA (cystine, ornithine, lysine, and arginine)
excess cystine in urine = recurrent hexagonal cystine stones
Tx - acetazolamide
142
What are some of the clinical effects of Zinc deficiency?
```
delayed wound healing
decreased immune response
rash around eyes, mouth, nose and anus (acrodermatitis enteropathica)
anorexia and diarrhea
growth retardation
decreased mental functioning
impaired night vision
infertility
```
143
Bluish colored lines of gingivae
Burton lines (iron toxicity)
144
What organs are primary affected by an excess of mercury? What are other symptoms?
kidneys and brain
acrodynia - peeling of the fingertips
peripheral neuropathy, tremor, excitability and insomnia
145
What are the symptoms of VitA toxicity?
```
N/V
vertigo
blurred vision
bone and joint pain
alopecia
dry skin
hepatic toxicity and enlargement
arthralgias
pseudotumor cerebri
ataxia
HA
teratogenic -> cleft palate and cardiac abnormalities
```
146
What clinical features would lead you to suspect that a patient has scurvy?
```
bleeding gums
poor wound healing
bruising/petechiae
anemia
hemarthrosis
cork screw hair
loose teeth
```
147
Vitamin C is necessary for the hydroxylation of which amino acids in collagen synthesis?
lysine and proline
148
Which enzymes are used to convert cholecalciferol (Vit D3) to calcitriol? (1,25-OH-D3)
25-hydroxylase (liver) and 1-alpha-hydroxylase (kidney)
149
A patient presents with convulsions and irritability. What vitamin deficiency is causing these symptoms?
Vit B6 (produces GABA) (pyridoxine)
150
Where is Vit B12 absorbed into the circulation?
distal ileum
151
Which vitamin deficiency is associated with peripheral neuropathy and glossitis?
Vit B12 and Vit B6
152
Which vitamin deficiency is associated with dermatitis, diarrhea, and dementia?
Vit B3 (niacin)
153
Which vitamin deficiency is associated with megaloblastic anemia?
Vit B9, Vit B12
154
Which vitamin deficiency is associated with pernicious anemia?
Vit B12
155
Which vitamin is used in oxidation/reduction reactions?
Vit B2 (riboflavin), B3
156
Which vitamin is used in carboxylation reactions?
Vit B7 (biotin), VitK
157
Which vitamin requires intrinsic factor for absorption?
Vit B12
158
Which vitamin is used by pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase?
Vit B1
159
Which vitamin deficiency can be caused by isoniazid use?
Vit B6, Vit B3
160
Which vitamin contains cobalt?
Vit B12 (cobalamin)
161
Which vitamin is critical for DNA synthesis?
Vit B9 and B12
162
Dilated cardiomyopathy, edema, polyneuropathy
Wet beriberi (Vit B1 def)
163
What is dry beriberi?
Vit B1 def - polyneuritis, symmetrical muscle wasting
