Biochem Cards

Front 1

ACAT (acetyl CoA cholesterol transferase)

Back 1

Cholesterol + fatty acyl CoA → cholesteryl esters + CoA In intestinal epithelial cells, ACAT is used to reesterify cholesterol for transport via chylomicrons (CEs are hydrolyzed in the gut for absorption) In other cells, ACAT is used to store cholesteryl esters for later use by the cell ACAT = intracellular Contrast to LCAT = extracellular

Front 2

adenosine deaminase (ADA)

Back 2

Adenosine → inosine Purine salvage pathway Path: ↓ADA can → SCID (↓ DNA synthesis → ↓ lymphocyte count)

Front 3

adenylyl cyclase

Back 3

ATP → cAMP Membrane-bound protein can catalyze many rxns as long as it stays bound to activated G protein Activated by α-subunit of Gs Inhibited by α-subunit of Gi

Front 4

alanine transaminase (ALT)

Back 4

Glutamate + pyruvate ← → α ketoglutarate + alanine Co-factor = pyridoxal phosphate (from B6) Forward rxn in muscle → alanine transport to liver for reverse reaction to make pyruvate → → glucose Found mainly in liver (muscle also) (so better indicator of liver dz than AST) ALT in liver key to provide substrates for gluconeogenesis – this is how alanine coming into the liver from skeletal muscle is converted to pyruvate

Front 5

alpha ketoglutarate dehydrogenase

Back 5

α-ketoglutarate → succinyl CoA irreversible step CoA→ CO2 NAD → NADH TCA cycle Same family as PDH so same 5 co-enzymes: NAD, FAD (from riboflavin [B2]), TPP (from thiamin [B1]), lipoic acid, coenzyme A (from panthothenate [B5]) (–) NADH

Front 6

aspartate transaminase (AST)

Back 6

Glutamate + oxaloacetate ← → aspartate + alpha-ketoglutarate (glutamate and A-KG are partners in most transaminase reactions Co-factor = pyridoxal phosphate (from B6) Freely reversible transfer of amino group Aspartate then a substrate of urea cycle Found in liver, heart, muscle, kidney, pancreas, blood cells Important in ddx liver dz

Front 7

ATP synthase

Back 7

ADP + Pi + H+ gradient → ATP Coupling of electron transport out of the mitochondrial matrix and ATP synthesis inside the matrix Oxidation of 1 NADH → 3 ATP Oxidation of 1 FADH2 → 2 ATP Pharm: oligomycin → inhibits ATP synthase → no ATP source for bacteria (only used for lab research, not clinically)

Front 8

branching enzyme

Back 8

glycogen → branched glycogen glycogenesis Transfers 6 or 7 unit glucose residues from end to middle of glycogen chain Makes α 1,6 linkage of branch point Defect: Andersen disease

Front 9

cAMP-dependent protein kinase A (PKA)

Back 9

Phosphorylates specific threonine and serine residues in signaling pathways when an external molecule binds to a GPCR Some molecules, P → activation; others, P → inactivation Glucagon binding to → … → PKA → inactive glycogen synthase-P, active phosphorylase kinase-P and glycogen phospohorylase-P Epi binding to β1 adrenergic receptors on cardiac cells → Gs → … PKA → P of slow Ca2+ channels → more channels open @ threshold → faster depolarization ADH → … → PKA → P of aquaporins → ↑ # H2O channels on apical membrane Histamine binds H2 receptors → … → PKA → ↑ H+ ion secretion ACTH → … → PKA → activate cholesterol ester hydrolase-P → ↑ free cholesterol formed and converted to pregnenolone in mitochondria Norepi → … → PKA → active hormone-sensitive lipase-P → release of FA’s from fat

Front 10

carbamoyl phosphate synthase I (CPS I)

Back 10

CO2 + NH4+ → carbamoyl phosphate rate-limiting step ATP → ADP Carbamoyl phosphate then → urea cycle 1 of 2 urea cycle steps that occurs in mitochondrial matrix (rest in cytop) Allosterically regulated by N-acetylglutamate ←⊕ arginine (essential a.a. during growth spurts) Path: starvation, excess protein (via intake or GI bleed) → ↑glutamate, acetyl CoA → ↑ N-acetylglutamate → ↑ CPS I activity Defect: urea cycle defect – hyperammonemia

Front 11

carbamoyl phosphate synthase II (CPS II)

Back 11

CO2 + glutamine → carbamoyl phosphate + glutamate ATP → ADP 1st step of de novo pyrimidine synthesis Carbamoyl phosphate becomes part of pyrimidine ring ⊕ ATP ⊕ PRPP (–) UTP

Front 12

carnitine acyltransferase I (CAT I)

Back 12

Carnitine → acylcarnitine Acyl CoA → CoA Conjugates long-chain fatty acids to carnitine → able to cross into mitochondrial matrix → … beta oxidation CAT I is bound to outer mitochondrial membrane (–) malonyl-CoA ←⊕ insulin/←(-) glucagon

Front 13

CETP (cholesterol ester transfer protein)

Back 13

Transfer of cholesterol esters from HDL → LDL, VLDL, chylomicrons (→ liver) while TG’s are simultaneously transferred from LDL, VLDL, chylomicrons → HDL (→ TG’s cleaved by hepatic lipase) CE’s only transferred to apoB-containing particles

Front 14

dihydrofolate reductase

Back 14

Folic acid → dihydrofolate → H4 folate (tetrahydrofolate) Reduction of dihydrofolate to tetrahydrofolate req’d b/f it can serve as a 1-C carrier again Pharm: trimethoprim (inhibits bacterial dihydrofolate reductase) antibiotic; methotrexate (inhibits human dihydrofolate reductase) cancer chemotherapy (blocks de novo syn of DNA precursors) (also used in Crohn’s but diff MOA)

Front 15

fatty acid synthase

Back 15

Acetyl CoA + malonyl CoA + NADPH → → → palmitate Fatty acid synthesis enzyme builds palmitate 2 carbons at a time

Front 16

fructose 1,6 bisphosphatase

Back 16

F1,6BP → F6P irreversible step Gluconeogenesis In cytosol (–) F2,6BP ←⊕insulin/←(-)glucagon Path: deficiency → hypoglycemia

Front 17

glucokinase

Back 17

Glucose → G6P irreversible step using ATP → ADP Irreversible 1st step of glycolysis Enzyme in liver and pancreatic β cells High K¬m High capacity No feedback inhibition (vs. hexokinase which is -- by G6P) Phosphorylates excess glucose to sequester it in the liver Path: deficiency→ MODY (mature onset diabetes of the youth) – rare form of diabetes characterized by mild hyperglycemia

Front 18

glucose 6-phosphatase

Back 18

G6P → glucose irreversible step Final step in gluconeogenesis and glycogenolysis Enzyme found in liver (not muscle) ER Path: deficiency → Von Gierke’s dz (Type I glycogen storage dz; most common GSD) = severe fasting hypoglycemia, ↑↑ glycogen in liver, ↑ blood lactate, hepatomegaly, hyperlipidemia, hyperuricemia (I never got into explanations of the latter two in class but FYI, the problem is the flood of G6P is forced into glycolysis→overproduction of P’d intermediates (sent into NT breakdown→uric acid), acetyl CoA which is forced into fatty acid synthesis → elevation of VLDL)

Front 19

glucose 6-phosphate dehydrogenase (G6PD)

Back 19

G6P → 6-phosphogluconolactone + NADPH irreversible Rate-limiting enzyme of HMP shunt/pentose phosphate pathway NADPH then → fatty acid and steroid synthasis, glutathione reduction and CYP450 Path: ↓ G6PD → ↓glutathione reduction → ↓ detox of free radicals/peroxides → hemolytic anemia w/Heinz bodies; triggered by ingestion of fava beans, drugs that ↑ free radical formation (classic: antimalarials) ☺ ↓ G6PD → ↑ malarial resistance ↓ G6PD = x-linked recessive; > f in Afr. descent

Front 20

glutamate dehydrogenase

Back 20

Glutamate → NH4+ + α ketoglutarate NAD → NADH Oxidative deamination occurs in mitochondria when energy supplies are low ⊕ ADP ⊕ GDP In the liver, glutamate is the main direct source of ammonia entering the urea cycle

Front 21

glutaminase

Back 21

Glutamine → glutamate + NH3 In liver, NH3 produced → urea cycle In kidneys = way of ridding body of excess ammonia

Front 22

glutamine synthetase

Back 22

Glutamate + NH4+ → glutamine irreversible rxn ATP → ADP High [ ] glutamine in blood b/c acting as non-toxic carrier of ammonia mainly occurs in muscle, liver and CNS (though enzyme found in all cells)

Front 23

glycogen phosphorylase

Back 23

Glycogen (n) + P → glycogen (n-1) + G1P Glycogenolysis ⊕ glucagon (liver) ⊕ epi (liver and muscle) (–) insulin (liver and muscle) ⊕ AMP (muscle) ⊕ ATP (muscle) Path: deficiency in skeletal muscle glycogen phosphorylase → McArdle’s disease (Type V glycogen storage dz) = ↑ glycogen in muscle but can’t break it down → painful muscle cramps, myoglobinuria w/strenuous exercise) deficiency in skeletal muscle glycogen phosphorylase→Hers disease = increased glycogen content, hypoglycemia

Front 24

glycogen synthase

Back 24

Glycogen (n) → glycogen (n+1) Using UDP-glucose → UDP ⊕ insulin (liver and muscle) ⊕ glucose (liver) (–) glucagon (liver) (–) epi (liver and muscle) P’d form is inactive form Creates α 1,4 linkages

Front 25

HGPRTase

Back 25

Hypoxanthine → IMP (→ AMP or GMP) or guanine → GMP for both PRPP → PPi Path: mutated X-linked HGPRT gene → Lesch-Nyhan syndrome → gout, retardation, self-mutilation, aggression, choreoathetosis

Front 26

HMG-CoA reductase

Back 26

Acetyl CoA → → HMG CoA → mevalonate → → cholesterol using NADPH → NADP Rate limiting step of de novo cholesterol synthesis (–) cholesterol (–) statins (e.g. lovastatin)

Front 27

hormone-sensitive lipase (triacylglycerol lipase)

Back 27

TG (n) → TG (n-1) + FA degrades TG’s stored in adipocytes during fasting state Released FA’s bind to serum albumin ⊕ glucagon ⊕ norepi (→ ↑cAMP → active PKA → phosphorylation of hormone-sensitive lipase) (–) insulin (+) norepi

Front 28

LCAT (lecithin cholesteryl acyltransferase)

Back 28

Catalyzes transfer of cholesterol into HDL particle after esterification of cholesterol apoA-1 required (Activates LCAT), as is lecithin (found in HDL membrane) → HDL w/cholesteryl ester inside can then → liver via HDL binding to SR-B1 scavenger receptor or hand off to VLDL, LDL Pharm: gemfibrozil (PPAR-alpha agonist) → activation of PPAR-alpha (1)→ upregulation of apoA-1 → ↑ LCAT activity →↑transfer of cholesterol from endothelial cells, macrophages, LDL, etc to HDL (raises HDL)

Front 29

lipoprotein lipase

Back 29

Degrades TG’s circulating in chylomicrons and VLDLs Extracellular enzyme of endothelial cells esp of muscle/fat apoC-II = Co-factor Heparin required as a cofactor (may connect LPL to CII) Chylomicron (TG with C-II, A, E, B-48) → chylomicron remnant (↓TG but add CE with E, B-48 still attached) VLDL (TG + CE with C-II, B-100, E attached) → IDL (↓ TG, CE with B-100, E still attached) → extract more FA’s from chylomicrons/VLDL → ↑ FA release which are then stored/metabolized in nearby cells ⊕ insulin (mainly in adipose)– hydrolyzing TG in particles in the bloodstream and bringing them into cells for storage Pharm: gemfibrozil (PPAR-alpha agonist) → lipoprotein lipase activation → ↓↓↓ [TG] Path: a Type I familial dyslipidemia (hyperchylomicronemia) is caused by lipoprotein lipase deficiency (or altered apo C-II) → chylomicrons, serum [TG], serum [cholesterol]

Front 30

ornithine transcarbamoylase

Back 30

Ornithine + carbamoyl phosphate → citrulline Urea cycle 1 of 2 steps that occurs in mitochondrial matrix (rest in cytop) Path: inherited ornithine transcarbamoylase deficiency → ↑orotate (b/c excess carbamoyl P shunted into nucleotide synth pathway→orotate is precursor of pyrimidine bases), hyperammonemia (→ ↓ α-ketoglutarate → ↓ TCA cycle - this part is only hypothesized as an explanation for the sx) tremor, slurred speech, somnolence, vomiting, cerebral edema, blurred vision (Tx = arginine, ammonia-sequestering drugs ie sodium benzoate)

Front 31

phosphofructokinase (PFK)

Back 31

F6P → F1,6BP irreversible step of glycolysis ⊕ AMP ⊕ ⊕ ⊕ F2,6BP ←⊕ insulin /←(-) glucagon (–) ATP (–) Rare defects→ exercise intolerance and hemolytic anemia, due to reliance of RBCs and muscle on glucose for energy

Front 32

phosphorylase kinase

Back 32

Glycogen phosphorylase (inactive)→ glycogen phosphorylase-P (active) → ↑ glycogenolysis ⊕ glucagon ⊕ epi ⊕ Ca2+ (–) insulin Active glycogen phosphorylase-P

Front 33

purine nucleoside phosphorylase

Back 33

Inosine → hypoxanthine or guanosine → guanine Purine salvage pathway PNP deficiency→immunodeficiency, mental retardation, muscle spasticity

Front 34

pyruvate carboxylase

Back 34

Pyruvate + CO2 → oxaloacetate irreversible step ATP → ADP First step of gluconeogenesis ⊕ acetyl CoA In mitochondria Requires biotin Path: deficiency pyruvate carboxylase → hypoglycemia

Front 35

pyruvate dehydrogenase (PDH)

Back 35

Pyruvate + CoA → acetyl CoA +CO2 NAD → NADH ⊕ NAD+/NADH ratio, ADP, Ca2+ (i.e., activated by exercise) (–) NADH, acetyl CoA, ATP 5 co-enzymes: NAD, FAD (from riboflavin [B2]), TPP (from thiamin [B1]), lipoic acid, coenzyme A (from panthothenate [B5]) Path: ↓PDH (congenital or B1 deficiency in alcs) → ↑ pyruvate, ↑ alanine → lactic acidosis

Front 36

pyruvate kinase

Back 36

PEP → pyruvate irreversible step Using ADP → ATP Last step of glycolysis ⊕ F1,6BP; this is a way of linking the energy requiring part of glycolysis (1st half) to the energy utilizing part of the pathway (2nd half); compare to F2,6BP (not a glycolytic intermediate), ⊕ glycolysis also, but at PFK (–) ATP (–) fatty acids (–) alanine Path: most common glycolytic enzyme deficiency associated w/hemolytic anemia

Front 37

thymidylate synthase

Back 37

dUMP → dTMP methylene H4 folate oxidized to H2 folate (dihydrofolate) during the folic acid cycle methylation of dUMP during deoxyribon’tide synthesis Inhibitors used as antichemotherapeutic agents

Front 38

transaminase

Back 38

R1 α a.a. + R2 α ketoacid ← → R2 α a.a. + R1 α ketoacid Transfer of amino groups E.g.: ALT, AST Cofactor = pyroxidal phosphate (from B6)

Front 39

transketolase

Back 39

Keto group transfer → ribose 5-phosphate (n’tide syn) or G3P or F3P (glycolytic intermediates Nonoxidative, reversible step of HMP shunt/pentose phosphate pathway Requires thiamin co-factor Path: ↓ thiamine → Wernicke-Korsakoff syndrome (alcs)

Front 40

tyrosine kinase receptor

Back 40

Insulin binding → receptor autophosphorylation → activation of insulin receptor substrates (IRS’s) → modulate other protein activity E.g., protein phosphatase I which then de-P’s glycogen synthase (activating it → ↑ glycogen synthesis); de-P’s and inactivates both phosphorylase kinase and glycogen phosphorylase (↓ glycogenolysis)

Front 41

xanthine oxidase

Back 41

Hypoxanthine → xanthine and xanthine → uric acid Last steps of purine catabolism Pharm: Allopurinol = hypoxanthine isomer that inhibits xanthine oxidase → ↓ uric acid production → treats chronic gout