Flashcards in Enzymes Deck (72):
1
Carbamoyl Phosphate Synthetase II
- Pyrimidine Synthesis (rate-limiting)
Glutamine + CO2 + 2ATP --> Carbamoyl phosphate
- Cytosol
- N from glutamine
2
UMP Synthase
- Pyrimidine Synthesis
Orotic acid + PRPP --> UMP
- Impaired in orotic aciduria
3
Ribonucleotide Reductase
- Pyrimidine Synthesis
UDP --> dUDP
- Inhibited by hydroxyurea (sickle cell, cancer)
4
Thymidylate Synthase
- Pyrimidine Synthesis
dUMP --> dTMP
- uses THF (have to have folic acid to synthesize DNA)
- Inhibited by 5-FU (cancer)
5
Dihydrofolate Reductase
- Pyrimidine Synthesis
Regenerates THF from DHF after it's used by thimidylate synthase
- Inhibited by methotrexate (eukaryotes), trimethoprim (prokaryotes), and pyrimethamine (protozoa)
6
Glutamine PRPP Amidotransferase
- Purine Synthesis (rate-limiting)
PRPP --> IMP
- Inhibited by 6-MP (cancer)
7
IMP Dehydrogenase
- Purine Synthesis
IMP --> GMP
- Inhibited by mycophenolate
8
Xanthine Oxidase
- Purine Salvage
Hypoxanthine --> xanthine
Xanthine --> uric acid
- Inhibited by allopurinol and febuxostate (gout)
- Metabolizes azathioprine and 6-MP (increases toxicity)
9
HGPRT
- Purine Salvage
Hypoxanthine --> IMP
Guanine --> GMP
- Deficient in Lesch Nyhan Syndrome
10
Adenosine Deaminase
- Purine salvage
Adenosine --> Inosine
- Deficiency causes SCID
11
Glucokinase
- Glycolysis (first committed step)
- Glycogen synthesis
Glucose --> glucose-6-phosphate
- Found in liver, beta cells of pancreas
- High Km (needs a lot of glucose)
- High Vmax (works quickly)
- Induced by insulin
- Mutation --> maturity onset diabetes of the young
12
Hexokinase
- Glycolysis (first commited step)
- Glycogen synthesis
Glucose--> glucose-6-phosphate
- Most tissues
- Low Km (higher affinity)
- Low Vmax (low capacity)
- Not induced by insulin
13
Phosphofructokinase-1
- Glycolysis (rate-limiting step)
- Requires ATP
F-6-P --> F-1,6-BP
- Stimulated by: AMP (not a lot of ATP around), F-2,6-BP
- Inhibited by: ATP (high energy state), citrate (substrate of TCA cycle)
14
Pyruvate Kinase
- Glycolysis
- Produces ATP
Phosphoenolpyruvate --> pyruvate --> TCA cycle
Stimulated by: F-1,6-BP (upstream substrate)
Inhibited by: ATP, alanine (high energy state)
15
Phosphofructokinase-2
- Glycolysis (regulating step)
F-6-P --> F-2,6-BP --> allosteric activator of PFK-1 (glycolysis substrate)
Stimulated by: insulin (fed state)
16
Fructose-bisphosphatase-2
- Glycolysis (regulating step)
F-2,6-BP --> F6P --> gluconeogenesis
Stimulated by: glucagon (fasting)
17
Pyruvate Carboxylase
- Gluconeogenesis
- Requires biotin
Pyruvate --> oxaloacetate
- Requires biotin
- Stimulated by: acetyl Co-A
18
PEP Carboxykinase
- Gluconeogenesis
Oxaloacetate --> PEP
19
Fructose-1,6-Bisphosphatase
- Gluconeogenesis (rate-limiting)
F-1,6-BP --> F6P
- Stimulated by: ATP (high energy)
- Inhibited by: AMP, F-2,6-BP (energy deficient)
20
Glucose-6-Phosphatase
- Gluconeogenesis (last step)
- Glycogenolysis (last step)
G6P --> glucose
- deficient in Von Gierke Disease
- NOT in muscles (can't do gluconeogenesis) - only reason muscle cells break down glycogen is for its own use (doesn't share energy)
21
Glycogen Synthase
- Glycogen synthesis (rate-limiting)
UDP-Glucose --> Glycogen
- Makes alpha-1,4-glycosidic linkages
- Stimulated by insulin
22
Glycogen Phosphorylase
- Glycogenolysis
Liberates G1P residues off branched glycogen until 4 glucose units remain on a branch
- Breaks alpha-1,4 linkage
- Inhibited by: ATP, G6P, glucose, insulin
- Stimulated by: glucagon (by activating GP kinase), Epi (Gs)
- Deficient in McArdle Disease (Type V)
23
Phosphoglucomutase
- Glycogenolysis
G1P --> G6P
24
Debranching Enzyme
- Glycogenolysis
4-alpha-D-glucanotransferase: removes 3 molecules of G1P from branch to linkage
alpha-1,6-glucosidase: cleaves off last residue --> liberates glucose
- Deficient in Cori Diseaes (Type III)
25
Pyruvate Carboxylase
- Pyruvate Metabolism
- Requires biotin
Pyruvate + ATP + CO2 --> oxaloacetate --> TCA cycle or gluconeogenesis
- Cofactor: biotin
26
Pyruvate Dehydrogenase
- Pyruvate Metabolism
- Requires B1, B2, B3, B5, lipoic acid
Pyruvate + NAD+ + CoA --> AcetylCoA + CO2 + NADH
- Transition from glycolysis to TCA cycle
- Cofactors: TPP (B1), lipoic acid (inhibited by arsenic - garlic breath), Coenzyme A (B5), FAD (B2), NAD+ (B3)
- Activated by: increased NAD+/NADH ratio, high ADP, high Ca2+
27
Lactic Acid Dehydrogenase
- Pyruvate Metabolism
- Requires B3
Pyruvate --> lactate (requires NADH) --> Cori Cycle
- End of anaerobic glycolysis (major pathway in RBCs, WBCs, kidney medulla, lens, testes, and cornea)
- For cells that like mitochondria
- Deficiency leads to exercise intolerance
28
Alanine Aminotransferase
- Pyruvate Metabolism
- Requires B6
Pyruvate --> Alanine --> Cahill Cycle
- Alanine carries amino groups to the liver from muscle
29
Citrate Synthase
- TCA Cycle
Acetyl-CoA (2C) + oxaloacetate (4C) --> Citrate (6C)
- Inhibited by ATP
30
Isocitrate Dehydrogenase
-TCA Cycle
Isocitrate (6C) --> CO2 + NADH + alpha-ketoglutarate (5C)
- Inhibited by: ATP, NADH
- Stimulated by: ADP
31
Alpha-Ketoglutarate Dehydrogenase
- TCA Cycle (highly regulated)
- Cofactors: B1, B2, B3, B5, lipoic acid
Alpha-KG (5C) --> CO2 + NADH + succinyl CoA (4C)
- Inhibited by: ATP, NADH, succinyl CoA
- Requires same cofactors as pyruvate dehydrogenase complex (B1, B2, B3, B5, lipoic acid)
32
Complex 1
- ETC (oxidative phosphorylation)
- NADH --> NAD+ --> 2.5 ATP
- Inhibited by Amytal (barbiturate), Rotenone (pesticide/fish poison), MPP (also causes Parkinson's)
33
Complex II (Succinate Dehydrogenase)
- ETC (oxidative phosphorylation)
FADH2 --> FAD --> 1.5 ATP
34
Complex III
- ETC (oxidative phosphorylation)
Inhibited by Antimycin A (fish poison)
35
Complex IV
- ETC (oxidative phosphorylation)
1/2 O2 + 2H+ --> H2O
- Inhibited by CN, sodium azide, CO, H2S
36
Complex V (ATPase)
- ETC (oxidative phosphorylation)
- Generates ATP
- Inhibited by Oligomycin (macrolide ABx)
37
Alanine Aminotransferase
- Transamination
- Cofactor: pyridoxal phosphate (B6)
Alanine + alpha-KG --> pyruvate + glutamate
- Marker for hepatocyte damage
38
Aspartate Transaminase
- Transamination
- Cofactor: pyridoxal phosphate (B6)
Aspartate + alpha-KG --> oxaloacetate + glutamate
- Marker for hepatocyte damage
39
G6P Dehydrogenase
- HMP Shunt (pentose phosphate pathway) [rate limiting step]
G6P + NADP+ --> 2 NADPH + Ribulose-5-P + CO2
- NADPH --> glutathione reduction inside RBCs, FA and cholesterol biosynthesis
- Ribulose-5-P --> PRPP --> nucleotide synthesis (ribose backbones)
- Inhibited by NADPH
- Deficiency --> hemolytic anemia
40
NADPH Oxidase
- Respiratory Burst
- Requires NADPH
O2 --> superoxide ion
- In phagolysosome
- Deficiency: chronic granulomatous disease
41
Superoxide Dismutase
- Respiratory burst
Superoxide ion --> hydrogen peroxide
- In phagolysosome
42
Myeloperoxidase
- Respiratory burst
Hydrogen peroxide + Cl- --> hypochlorous acid (bleach)
- In phagolysosome
43
Glutathione Peroxidase
- RBC Detox
H2O2 + reduced glutathione (important antioxidant) --> H2O + glutathione disulfide (oxidized)
44
Glutathione Reductase
- Uses NADPH (from G6PD)
NADPH + glutathione disulfide (oxidized) --> NADP+ + reduced glutathione
45
Fructokinase
- Fructose metabolism
- Requires ATP
Fructose + ATP --> F1P
- Defect: essential fructosuria (benign)
46
Aldolase B
- Fructose metabolism
F1P --> dihydroxyacetone P and glyceraldehyde
- Defect: fructose intolerance (inhibits glycogenolysis and gluconeogenesis --> fasting hypoglycemia)
47
Galactokinase
- Galactose metabolism
- Requires ATP
Galactose + ATP --> Galactose-1-P
- Defect: galactokinase deficiency (infantile cataracts)
48
Aldose Reductase
- Galactose metabolism
Galactose --> galactitol
- too much galactitol --> cataracts
49
Galactose-1-Phosphate Uridyltransferase
- Galactose metabolism
Galactose-1-P + UDP-Glucose --> Glucose-1-P + UDP-Galactose --> glycolysis/glycogenolysis
- Defect: classic galactosemia
50
HMG-CoA Synthase
- Ketogenesis (rate-limiting)
Makes ketone bodies during starvation
51
Alcohol Dehydrogenase
- Ethanol metabolism
- NAD+ is limiting reagent
Ethanol + NAD+ --> Acetaldehyde + NADH
- 0-order kinetics
- Acetaldehyde is what causes hangover
- Inhibited by Fomepizole (used for methanol or ethylene glycol poisoning)
52
Acetaldehyde Dehydrogenase
- Ethanol metabolism
- NAD+ is limiting reagent
Acetaldehyde + NAD+ --> Acetate + NADH
- Inhibited by disulfiram (acetaldehyde accumulates --> hangover sx)
53
ApoE
- Lipid transport
Mediates remnant uptake
54
Apo A-1
- Lipid transport
Activates LCAT --> catalyzes esterification of cholesterol
- Nascent HDL --> mature HDL
55
Apo C-II
- Lipid transport
Lipoprotein lipase cofactor
- Deficient in Type I (Hyperchylomicronemia)
56
Apo B-48
- Lipid transport
Mediates chylomicron secretion
57
Apo B-100
- Lipid transport
Mediates VLDL secretion
- Binds LDL R
- Defective binding in Type IIa (familial hypercholesterolemia)
58
HMG-CoA Reductase
- Cholesterol synthesis (rate limiting step)
Converts HMG-CoA to mevalonate
- Induced by insulin
- Inhibited by statins
- Cholesterol synthesis starts with acetyl CoA
59
Acetyl CoA Carboxylase
- FA Synthesis (rate limiting step)
- Cytoplasm of hepatocytes
60
Carnitine Acyltransferase 1 (Caritine Palmitoyltransferase 1)
- FA Degradation (rate limiting step)
- Mitochondrial matrix
61
Phenylalanine Hydroxylase
- Catecholamine synthesis/tyrosine catabolism
- Cofactor: BH4
Phenylalanine --> Tyrosine
- Tyrosine used to make thyroxine
- Deficient: PKU
62
Tyrosine Hydroxylase
- Catecholamine synthesis/ tyrosine catabolism
- Cofactor: BH4
Tyrosine --> Dopa
- Dopa used to make melanin
63
Dopa Decarboxylase
- Catecholamine synthesis/tyrosine catabolism
- Cofactor: B6
DOPA --> Dopamine
- Inhibited by Carbidopa (rx for Parkinson's)
64
Dopa-beta-hydroxylase
- Catecholamine synthesis/tyrosine catabolism
- Cofactor: Vit C
Dopamine --> NE
Deficiency: nasal congestion, ptosis, orthostatic hypotension
65
Phenylethanolamine-N-methyltransferase
- Catecholamine synthesis/tyrosine catabolism
- Cofactor: SAM (transfers methyl groups)
NE --> Epi
- Stimulated by cortisol
66
Carbamoyl Phosphate Synthetase I
- Urea cycle (rate-limiting step)
- Requires ATP
CO2 + NH3 --> Carbamoyl phosphate
- In mitochondria
67
Ornithine Transcarbamylase
- Urea cycle
Carbamoyl phosphate + ornithine --> citrulline
68
Tyrosinase
- Catecholamine synthesis/tyrosine catabolism
Dopa --> melanin
- Deficiency: albinism
69
Homogentisate Oxidase
- Catecholamine synthesis/tyrosine catabolism
Homogentisic acid (from Tyr) --> maleylacetoacetic acid --> fumarate --> TCA cycle
- Deficiency: alkaptonuria (ochronosis, black urine)
70
Cystathione Synthase
- Homocysteine metabolism
- Cofactor: B6
Serine + homocysteine --> cystathione
Deficiency: homocystinuria
71
Methionine Synthase
- Homocysteine metabolism
- Cofactor: B12
Homosysteine --> methionine
Deficiency: homocystinuria
72