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USMLE - Biochemistry

mlinnie's version from 2018-11-12 00:05

Important Enzymes in Metabolic Processes

Glycolysis (RLS)Phosphofructokinase-1
Gluconeogenesis (RLS)Fructose-1,6-bisphosphatase
TCA cycle (RLS)Isocitrate dehydrogenase
Glycogen synthesis (RLS)Glycogen synthase
Glycogenolysis (RLS)Glycogen phosphorylase
HMP Shunt (RLS)Glucose-6-Phosphate Dehydrogenase
De novo pyrimidine synthesis (RLS)Carbamoyl Phosphate Synthetase II
De novo purine synthesis (RLS)Glutamine-PRPP aminotransferase
Urea cycle (RLS)Carbomyl Phosphate Synthetase I
Fatty acid synthesis (RLS)Acetyl-CoA Carboxylase
Fatty acid oxidatio (RLS)nCarnitine acyltransferase I
Ketogenesis (RLS)HMG-CoA synthase
Cholesterol synthesis (RLS)HMG-CoA reductase
Bile acid synthesis (from cholesterol) (cholesterol to bile acid) (RLS)7 α hydroxylase
Heme synthesis (RLS)δ-amino levulinate synthetase (ALAS)
Folate SynthesisDihydrofolate reductase (DHF)
Bilirubin ConjugationUDP-Glucuronyl transferase
Clotting Factor 2,7,9,10, C & K activationVitamin K carboxylation
Homocysteine to MethionineHomocysteine methyltransferase
Production of Succinyl-CoA (for TCA) from MethyMalonyl-CoAMethylMalonyl CoA Mutase
Maple Syrup Urine dzBranched-Chain alpha-keto acid Dehydrogenase (branched-chain AAs (ILV) in urine)
Galactokinase deficiencyGalactokinase
Classic GalactosemiaGlactose-1-Phosphate Uridyltransferase
Essential FructosuriaFructokinase
Fructose IntoleranceAldolase B
Lactose IntoleranceLactase
Ethanol metabolismAlcohol dehydrogenase (Rate limiting = NAD+)
Acetaldehyde metabolismAcetaldehyde dehydrogenase (Rate limiting = NAD+)
Gilbert's Syndromemildly ↓ UDP-glucuronyl transferase
Crigler-Najjar Syndrome Type Ino UDP-glucuronyl transferase
PKUPhenylalanine hydroxylase, TetraHydroBiopterin (THB)
Alkaptonuriahomogenistic acid oxidase
Homocystinuriacystathionine synthase or homocysteine methyltransferase
CystinuriaCOLA transporter in PCT of kidney
Hartnup Disease↓neutral AA transporter in kidneys & enterocytes
Lead PoisoningFerrochelatase & ALA dehydrogenase (ALAD)
Acute intermitted porphyriaPorphobilinogen deaminase (↑ Porphobilinogen)
Porphyria cutanea tardaUroporphyrinogen decarboxylase (↑ Uroporphyrin) (count dracula - europe)
Orotic Aciduria↓ UMP synthase (↑ orotic acid, normal NH3+) (de novo pyrimidine synthesis)
OTC (Orinithing Transcarboxylase Deficiencency )↑ orotic acid, ↑ NH3+ (urea cycle)
Final enzyme of Uric acid productionXanthine oxidase
Gout or Lesh-NyhanHGPRT (↑ uric acid production, ↓purine salvage)
SCIDAdenosine Deaminase

Drug Enzymes

Question Answer
6-mercaptopurineblocks purine synthesis
Hydroxyurea↓ ribonucleotide
5-Flurouracil↓ thymidylate synthase (↓ deoxythymdine monophosphate)
Methotraxate/ Trimethoprim (Trim)↓ dihydrofolate reductase (↓dTMP)

Rate Limiting Enzymes in Metabolic Processes

GlycolysisPhosphofructokinase-1AMP, Fructose-2,6-BPATP, Citrate
GluconeogenesisFructose-1,6-bisphosphataseATPAMP, Fructose-2,6-BP
TCA cycleIsocitrate dehydrogenaseADPATP, NADH
Glycogen synthesisGlycogen synthaseGlucose, InsulinEpinephrine, Glucagon
GlycogenolysisGlycogen phosphorylaseAMP, Epinephrine, GlucagonATP, Insulin
HMP ShuntGlucose-6-Phosphate DehydrogenaseNADP+NADPH
De novo pyrimidine synthesisCarbamoyl Phosphate Synthetase IIn/an/a
De novo purine synthesisGlutamine-PRPP aminotransferasen/aAMP, IMP, GMP
Urea cycleCarbomyl Phosphate Synthetase IN-acetylglutamaten/a
Fatty acid synthesisAcetyl-CoA CarboxylaseGlucose, Insulin, CitrateGlucagon, Palmitoyl-CoA
Fatty acid oxidationCarnitine acyltransferase In/aMalonyl-CoA
KetogenesisHMG-CoA synthasen/an/a
Cholesterol synthesisHMG-CoA reductaseInsulin, ThyroxineGlucagon, Cholesterol

End products

ProcessEnd Product
Purineuric acid
Pyramidinebeta alanine,bets amino isoButyric acid,ammonia
FA oxidationacetyl coa
De novo purine symthIMP

Glycolysis (important enzymes) - CYTOSOL

Glucose --> + P --> G+P --> Fructose+P --> +P--> F+P+P --> ---> Pyruvate
Glucose to Glucose-6-PhosphateGlucokinase (liver,kidney,small intestine = high Km) /Hexokinase
Fructose-6-Phosphate to Fructose-1,6-BisphosphatePhosphoFructose Kinase 1 (Rate Limiting Step)
Phosphoenol Pyruvate to PyruvatePyruvate Kinase
Fructose-6-Phosphate to Fructose-2,6-BisphosphatePhosphoFructose Kinase 2 (not part of glycolysis)--> inc Glycolysis

GLUCOneogenesis (important enzymes) - ONLY in LIVER + KIDNEYS + SMALL INTESTINES - CYTOSOL

Pyruvate --> another intermediate (Oxaloacetate) --> pre-Pyruvate --> --> Fructose+P+P --> Fructose+P --> Glucose+P --> Glucose
Pyruvate to Oxaloacetate(in Mitochindria) Pyruvate Carboxylase + Biotin (b/c Pyruvate Kinase is irreversible - need to convert pyruvate into something else)
Oxaloacetate to PhosphoEnol Pyruvate(in cytoplasm) PEP (PhosphoEnol Pyruvate) CarboxyKinase
Fructose-1,6-Bisphosphate to Fructose-6-Phosphate(in cytoplasm) Fructose-1,6-Bisphosphatase
Glucose-6-Phosphate to Glucose(in ER) Glucose-6-Phosphatase

Glycogenesis (Glucose --> Glycogen) - CYTOSOL

Glucose --> G-6-P --> G-1-P --> Glycogen
Liver & Muscle
alpha (1,4) bonds = length
alpha (1,6) bonds = branches


Question Answer
Glucose to GlycogenGlycogen Synthase

Glycogenolysis (Glycogen --> Glucose) - CYTOSOL

Glycogen --> G-1-P --> G-6-P --> Glucose
*Liver & Skeletal Muscle (No Glucose-6-Phosphatase = aka, can't ship out glucose into blood)
Question Answer
Glycogen to GlucoseGlycogen Phosphorylase

Glycogen Storage Disease (Autosomal Recessive)

Von = type One, Pompe = Pump (heart = cardiomegaly), ABCD --> Cori = debranching enzyme defect, McArdle = Muscle
DiseaseDeficiency & Findings
Von Gerke's Disease (Type I - one)can't ship out Glucose (no Glucose-6-Phosphatase).
**inc glycogen in liver (hepatomegaly), if fast --> severe hyperglycemia!
Pompe's Disease (Type II )can't break down Glycogen (no lysosomal alpha-1,4 glucosidase = can't break down alpha-1,4 bonds).
**Pompe = Pump --> Cardiomegaly
Cori's Disease (Type III)no de-branching enzyme (can't breakdown alpha-1,6 bonds , no alpha-1,6 glocosidase).
**Still can breakdown longer bonds (alpha-1,4).
McArdle's Disease (Type V)can't break down any glycogen in Muscle (no glycogen phosphorylase).
**inc glycogen in muscle, can't break down --> cramps + myoglobinuria w/ exercise


Question Answer
Glycogen phosphorylase deficiencyMcArdle (Type V)
Glucose-6-Phosphatase deficiencyVon Gierke (Type I)
Lactic Acidosis , hyperlipidemia, hyperuricemia (gout)Von Gierke (Type I)
alpha-1,6-glucosidase deficiencyCori (Type III)
alpha-1,4-glucosidase deficiencyPompe (Type II)
CardiomegalyPompe (Type II)
Diaphragm weakness then respiratory failurePompe (Type II)
Increased glycogen in liver, severe fasting hypoglycemiaVon Gierke (Type I)
Hepatomegaly, Hypoglycemia, hyperlipidemia (normal kidneys, lactate and uric acid)Von Gierke (Type I)
Painful muscle cramps, myoglobinuria w/ exerciseMcArdle (Type V)
Severe hepatosplenomegaly, enlarged kidneysVon Gierke (Type I)
Von Gierke (Type I)no glycose-6-phosphatase, lactic acidosis, severe hypoglycemia
Pompe (Type II)no alpha-1,4-glucosidase, cardiomegaly
Cori (Type III)no de-branching enzyme (alpha-1,6) (like Type I but less severe)
McArdle (Type V)muscle, no glycogen phosphorylase

Pyruvate Fates

Glycolysis --> end product = Pyruvate
*Uses of Pyruvate
ProcessAssociated ProductMechanism
Cori CycleLactic acidmuscle/RBC breakdown glucose into pyruvate --> Lactate Dehydrogenase --> converted to lactate --> spilled into blood --> goes to liver --> converted back to glucose --> spilled into blood --> used up by muscles & RBCs
Alanine CycleAlaninemuscle breakdown glucose into pyruvate --> converted to alanine --> alanine & glutamine are Nitrogen carriers in the blood --> go to liver --> alanine dumps the nitrogen into hepatocytes --> alanine converted to pyruvate --> pyruvate to glucose --> spilled into the blood --> used up by muscles
GluconeogenesisOxaloacetatepyruvate --> pyruvate carboxylase + biotin --> converted to oxaloacetate --> converted to PEP --> F-1,6-Bisphosphate --> F-6-P --> G-6-P --> Glucose --> spilled into blood --> used up by muscles and RBCs
TCAAcetyl CoApyruvate --> pyruvate dehydrogenase --> Acetyl CoA --> TCA --> 3NADH + 1FADH2 + 2CO2 + 1 GTP per pyruvate (2x per glucose)


Pyruvate --> Pyruvate Dehydrogenase --> Acetyl-CoA + Oxaloacetate --> Citrate Synthese --> Citrate --> IsoCitrate --> Isocitrate Dehydrogenase --> alpha-KetoGlutarate --> alpha-KetoGlutarate Dehydrogenase --> Succinyl CoA --> Succinate --> Fumarate --> Malate --> Oxaloacetate
End product of TCA = 3 NADH + 1 FADH + 1 GTP per Acetyl CoA x2 (Glucose --> 2x Acetyl CoA)


ProcessEnzymeAdditional cofactors
Pyruvate --> Acetyl CoAPyruvate dehydrogenase5 cofactors (B1= thiamine, B2 = FAD, B3 = NAD, B5 = CoA, Lipoic Acid)
Acetyl CoA + Oxaloacetate --> CitrateCitrate Synthaseno cofactors
Isocitrate --> alpha-KetoGlutarateIsoCitrate Dehydrogenase (RLS)no cofactors
alpha-KetoGlutarate --> Succinyl-CoAalpha-KetoGlutarate Dehydrogenase5 cofactors (B1= thiamine, B2 = FAD, B3 = NAD, B5 = CoA, Lipoic Acid)


From TCA cycle = 3 NADH + 1 FADH2 + 1 ATP per Acetyl CoA
*Goal = inc H+ concentration in the INTER-MITOCHONDRIAL SPACE for Complex V (ATPase = accepts H+ --> outputs ATP)


ComplexActionInhibited by
Complex INADH --> NAD+Rotenone
Complex IIFADH2 --> FADn/a
Complex III*needs CoEnzyme Q (CoQ)Antimycin A
Complex IVO2 --> H2OCyanide, CO
Complex VH+ --> ATPOligomycin


Electron Transport InhibitorsRotenone (I), Anti(mycin) A (III), Cyanide (IV), CO (IV)block complexes (I-IV), dec H+ gradient = block ATP synthesis
ATP Synthase InhibitorsOligo(mycin) (V)blocks complex V, inc in H+ gradient but NO ATP synthesis
Uncoupling Agents2,4 DNP, Aspirininc permeability of membrane (H+ leaks out) = dec in H+ gradient = ATP synthesis stops, but electron transport continues (HEAT!!)

Aerobic Metabolism

Glycolysis = 2 ATP + 2 NADH + 2 pyruvate
Pyruvate --> Acetyl CoA = 1 NADH/pyruvate = 2 NADH total
TCA = 3 NADH + 1 FADH2 + 1 GTP x2 = 6 NADH + 2 FADH2 + 2 GTP


Total = 4 ATP + 10 NADH (x2.5) + 2 FADH2 (x1.5) = 32 ATP/glucose


Question Answer
Glucose-6-Phosphate to Ribulose (PRPP) + NADPHGlucose-6-Phosphate Dehydrogenase


*Respiratory Burst
Question Answer
O2 to O2-*NADPH oxidase
O2-* to H2O2Superoxide dismutase
H2O2 to HOCl*Metaloperoxidase


*Reducing Reactive-Oxygen Species
Question Answer
H2O2 to H20Glutathione peroxidase
reduce Glutathione byNADPH

Carbohydrate Enzyme Deficiencies

Question Answer
Essential Fructosuria (benign - fructose secreted in urine)Fructokinase
Fructose Intolerance (accumulation of F-1-P = hypoglycemia, jaundice)Deficiency of Aldolase B
Glactokinase Deficiency (Galacticol accumulation = cataract)Galactokinase
Classic Galactosemia (accumulation of Galactose-1-p = cataract, failure to thrive, jaundice)Galactose-1-Phosphate Uridyltransferase
Complications of Diabetes (nephropathy, neuropathy, retinitis)Aldose reductase --> sorbitol (but no Sorbitol dehydrogenase --> Fructose)


Ethanol to AldehydeAlcohol dehydrogenase (NAD+ --> NADH)
Aldehyde to AcetateAcetaldehyde dehydrogenase (NAD+ --> NADH)


**if too much Ethanol --> use up NAD+ --> excess NADH --> to get more NAD+ (Pyruvate --> Lactate & Oxaloacetate --> malate) --> dec TCA substrates & no gluconeogenesis --> HYPOGLYCEMIA


**Ketones --> brain metabolizes ketones --> 2 Acetyl-CoA