Enzymes Flashcards
Carbamoyl Phosphate Synthetase II
- Pyrimidine Synthesis (rate-limiting)
Glutamine + CO2 + 2ATP –> Carbamoyl phosphate
- Cytosol
- N from glutamine
UMP Synthase
- Pyrimidine Synthesis
Orotic acid + PRPP –> UMP
- Impaired in orotic aciduria
Ribonucleotide Reductase
- Pyrimidine Synthesis
UDP –> dUDP
- Inhibited by hydroxyurea (sickle cell, cancer)
Thymidylate Synthase
- Pyrimidine Synthesis
dUMP –> dTMP
- uses THF (have to have folic acid to synthesize DNA)
- Inhibited by 5-FU (cancer)
Dihydrofolate Reductase
- Pyrimidine Synthesis
Regenerates THF from DHF after it’s used by thimidylate synthase
- Inhibited by methotrexate (eukaryotes), trimethoprim (prokaryotes), and pyrimethamine (protozoa)
Glutamine PRPP Amidotransferase
- Purine Synthesis (rate-limiting)
PRPP –> IMP
- Inhibited by 6-MP (cancer)
IMP Dehydrogenase
- Purine Synthesis
IMP –> GMP
- Inhibited by mycophenolate
Xanthine Oxidase
- Purine Salvage
Hypoxanthine –> xanthine
Xanthine –> uric acid
- Inhibited by allopurinol and febuxostate (gout)
- Metabolizes azathioprine and 6-MP (increases toxicity)
HGPRT
- Purine Salvage
Hypoxanthine –> IMP
Guanine –> GMP
- Deficient in Lesch Nyhan Syndrome
Adenosine Deaminase
- Purine salvage
Adenosine –> Inosine
- Deficiency causes SCID
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
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
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)
Pyruvate Kinase
- Glycolysis
- Produces ATP
Phosphoenolpyruvate –> pyruvate –> TCA cycle
Stimulated by: F-1,6-BP (upstream substrate)
Inhibited by: ATP, alanine (high energy state)
Phosphofructokinase-2
- Glycolysis (regulating step)
F-6-P –> F-2,6-BP –> allosteric activator of PFK-1 (glycolysis substrate)
Stimulated by: insulin (fed state)
Fructose-bisphosphatase-2
- Glycolysis (regulating step)
F-2,6-BP –> F6P –> gluconeogenesis
Stimulated by: glucagon (fasting)
Pyruvate Carboxylase
- Gluconeogenesis
- Requires biotin
Pyruvate –> oxaloacetate
- Requires biotin
- Stimulated by: acetyl Co-A
PEP Carboxykinase
- Gluconeogenesis
Oxaloacetate –> PEP
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)
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)
Glycogen Synthase
- Glycogen synthesis (rate-limiting)
UDP-Glucose –> Glycogen
- Makes alpha-1,4-glycosidic linkages
- Stimulated by insulin
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)
Phosphoglucomutase
- Glycogenolysis
G1P –> G6P
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)
Pyruvate Carboxylase
- Pyruvate Metabolism
- Requires biotin
Pyruvate + ATP + CO2 –> oxaloacetate –> TCA cycle or gluconeogenesis
- Cofactor: biotin
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+
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
Alanine Aminotransferase
- Pyruvate Metabolism
- Requires B6
Pyruvate –> Alanine –> Cahill Cycle
- Alanine carries amino groups to the liver from muscle
Citrate Synthase
- TCA Cycle
Acetyl-CoA (2C) + oxaloacetate (4C) –> Citrate (6C)
- Inhibited by ATP
Isocitrate Dehydrogenase
-TCA Cycle
Isocitrate (6C) –> CO2 + NADH + alpha-ketoglutarate (5C)
- Inhibited by: ATP, NADH
- Stimulated by: ADP
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)
Complex 1
- ETC (oxidative phosphorylation)
- NADH –> NAD+ –> 2.5 ATP
- Inhibited by Amytal (barbiturate), Rotenone (pesticide/fish poison), MPP (also causes Parkinson’s)
Complex II (Succinate Dehydrogenase) - ETC (oxidative phosphorylation)
FADH2 –> FAD –> 1.5 ATP
Complex III
- ETC (oxidative phosphorylation)
Inhibited by Antimycin A (fish poison)
Complex IV
- ETC (oxidative phosphorylation)
1/2 O2 + 2H+ –> H2O
- Inhibited by CN, sodium azide, CO, H2S
Complex V (ATPase) - ETC (oxidative phosphorylation)
- Generates ATP
- Inhibited by Oligomycin (macrolide ABx)
Alanine Aminotransferase
- Transamination
- Cofactor: pyridoxal phosphate (B6)
Alanine + alpha-KG –> pyruvate + glutamate
- Marker for hepatocyte damage
Aspartate Transaminase
- Transamination
- Cofactor: pyridoxal phosphate (B6)
Aspartate + alpha-KG –> oxaloacetate + glutamate
- Marker for hepatocyte damage
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
NADPH Oxidase
- Respiratory Burst
- Requires NADPH
O2 –> superoxide ion
- In phagolysosome
- Deficiency: chronic granulomatous disease
Superoxide Dismutase
- Respiratory burst
Superoxide ion –> hydrogen peroxide
- In phagolysosome
Myeloperoxidase
- Respiratory burst
Hydrogen peroxide + Cl- –> hypochlorous acid (bleach)
- In phagolysosome
Glutathione Peroxidase
- RBC Detox
H2O2 + reduced glutathione (important antioxidant) –> H2O + glutathione disulfide (oxidized)
Glutathione Reductase
- Uses NADPH (from G6PD)
NADPH + glutathione disulfide (oxidized) –> NADP+ + reduced glutathione
Fructokinase
- Fructose metabolism
- Requires ATP
Fructose + ATP –> F1P
- Defect: essential fructosuria (benign)
Aldolase B
- Fructose metabolism
F1P –> dihydroxyacetone P and glyceraldehyde
- Defect: fructose intolerance (inhibits glycogenolysis and gluconeogenesis –> fasting hypoglycemia)
Galactokinase
- Galactose metabolism
- Requires ATP
Galactose + ATP –> Galactose-1-P
- Defect: galactokinase deficiency (infantile cataracts)
Aldose Reductase
- Galactose metabolism
Galactose –> galactitol
- too much galactitol –> cataracts
Galactose-1-Phosphate Uridyltransferase
- Galactose metabolism
Galactose-1-P + UDP-Glucose –> Glucose-1-P + UDP-Galactose –> glycolysis/glycogenolysis
- Defect: classic galactosemia
HMG-CoA Synthase
- Ketogenesis (rate-limiting)
Makes ketone bodies during starvation
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)
Acetaldehyde Dehydrogenase
- Ethanol metabolism
- NAD+ is limiting reagent
Acetaldehyde + NAD+ –> Acetate + NADH
- Inhibited by disulfiram (acetaldehyde accumulates –> hangover sx)
ApoE
- Lipid transport
Mediates remnant uptake
Apo A-1
- Lipid transport
Activates LCAT –> catalyzes esterification of cholesterol
- Nascent HDL –> mature HDL
Apo C-II
- Lipid transport
Lipoprotein lipase cofactor
- Deficient in Type I (Hyperchylomicronemia)
Apo B-48
- Lipid transport
Mediates chylomicron secretion
Apo B-100
- Lipid transport
Mediates VLDL secretion
- Binds LDL R
- Defective binding in Type IIa (familial hypercholesterolemia)
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
Acetyl CoA Carboxylase
- FA Synthesis (rate limiting step)
- Cytoplasm of hepatocytes
Carnitine Acyltransferase 1 (Caritine Palmitoyltransferase 1)
- FA Degradation (rate limiting step)
- Mitochondrial matrix
Phenylalanine Hydroxylase
- Catecholamine synthesis/tyrosine catabolism
- Cofactor: BH4
Phenylalanine –> Tyrosine
- Tyrosine used to make thyroxine
- Deficient: PKU
Tyrosine Hydroxylase
- Catecholamine synthesis/ tyrosine catabolism
- Cofactor: BH4
Tyrosine –> Dopa
- Dopa used to make melanin
Dopa Decarboxylase
- Catecholamine synthesis/tyrosine catabolism
- Cofactor: B6
DOPA –> Dopamine
- Inhibited by Carbidopa (rx for Parkinson’s)
Dopa-beta-hydroxylase
- Catecholamine synthesis/tyrosine catabolism
- Cofactor: Vit C
Dopamine –> NE
Deficiency: nasal congestion, ptosis, orthostatic hypotension
Phenylethanolamine-N-methyltransferase
- Catecholamine synthesis/tyrosine catabolism
- Cofactor: SAM (transfers methyl groups)
NE –> Epi
- Stimulated by cortisol
Carbamoyl Phosphate Synthetase I
- Urea cycle (rate-limiting step)
- Requires ATP
CO2 + NH3 –> Carbamoyl phosphate
- In mitochondria
Ornithine Transcarbamylase
- Urea cycle
Carbamoyl phosphate + ornithine –> citrulline
Tyrosinase
- Catecholamine synthesis/tyrosine catabolism
Dopa –> melanin
- Deficiency: albinism
Homogentisate Oxidase
- Catecholamine synthesis/tyrosine catabolism
Homogentisic acid (from Tyr) --> maleylacetoacetic acid --> fumarate --> TCA cycle - Deficiency: alkaptonuria (ochronosis, black urine)
Cystathione Synthase
- Homocysteine metabolism
- Cofactor: B6
Serine + homocysteine –> cystathione
Deficiency: homocystinuria
Methionine Synthase
- Homocysteine metabolism
- Cofactor: B12
Homosysteine –> methionine
Deficiency: homocystinuria
Alpha-ketoacid Dehydrogenase
- AA metabolism
- Cofactors: thiamine pyrophosphate, lipoate, coenzyme A, FAD, NAD
Degrades branched AA (isoleucine, leucine, valine)
Deficiency: maple syrup urine disease
