USMLE STEP 1: FIRST AID 2016: SECTION 2: BIOCHEMISTRY- METABOLISM – Flashcards
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NAME 2 METABOLISM SITES
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Mitochondria & Cytoplasm (pg. 83)
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WHAT TYPES OF METABOLISM OCCUR IN MITOCHONDRIA?
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-Fatty acid oxidation (β-oxidation) -Acetyl-CoA production -TCA cycle -Oxidative phosphorylation -Ketogenesis (pg. 83)
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WHAT TYPES OF METABOLISM OCCUR IN CYTOPLASM?
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-Glycolysis -HMP shunt -Synthesis of steroids (SER) -Proteins (RER) -Fatty Acids -Cholesterol -Nucleotides (pg.83)
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WHAT TYPES OF METABOLISM OCCUR IN BOTH MITOCHONDRIA AND CYTOPLASM?
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-Heme synthesis -Urea cycle -Gluconeogenesis (pg.83)
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KINASE FUNCTION
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- Catalyzes transfer of phosphate group from high energy molecule (ATP) to substrate (pg. 84)
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PHOSPHORYLASE FUNCTION
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- Adds inorganic phosphate onto substrate without using ATP. (pg. 84)
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PHOSPHATASE FUNCTION
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- Removes phosphate group from substrate. (pg. 84)
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DEHYDROGENASE FUNCTION
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- Catalyzes oxidation-reduction reactions. (pg. 84)
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HYDROXYLASE FUNCTION
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- Adds hydroxyl group (-OH) onto substrate. (pg. 84)
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CARBOXYLASE FUNCTION
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- Transfers CO2 groups with the help of biotin. (pg. 84)
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MUTASE FUNCTION
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- Relocates a functional group within a molecule. (pg. 84)
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RATE DETERMINING ENZYME OF GLYCOLYSIS?
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Phosphofructokinase (PFK-1) (pg. 84)
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RATE DETERMINING ENZYME OF GLUCONEOGENESIS?
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Fructose-1,6-bisphosphatase (pg. 84)
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RATE DETERMINING ENZYME OF TCA CYCLE?
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Isocitrate dehydrogenase (pg. 84)
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RATE DETERMINING ENZYME OF GLYCOGENESIS?
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Glycogen synthase. (pg. 84)
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RATE DETERMINING ENZYME OF GLYCOGENOLYSIS?
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Glycogen phosphorylase (pg. 84)
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RATE DETERMINING ENZYME OF HMP SHUNT?
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Glucose-6-phosphate dehydrogenase (G6PD) (pg. 84)
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RATE DETERMINING ENZYME OF DE NOVO PYRIMIDINE SYNTHESIS?
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Carbamoyl phosphate synthetase 2 (pg. 84)
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RATE DETERMINING ENZYME OF DE NOVO PURINE SYNTHESIS?
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Glutamine-phosphoribosylpyrophosphate (PRPP) amidotransferase (pg. 84)
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RATE DETERMINING ENZYME OF UREA CYCLE?
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Carbamoyl phosphate synthetase 1
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RATE DETERMINING ENZYME OF FATTY ACID SYNTHESIS?
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Acetyl-CoA carboxylase (ACC) (pg. 84)
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RATE DETERMINING ENZYME OF FATTY ACID OXIDATION?
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Carnitine acyltransferase 1 (pg. 84)
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RATE DETERMINING ENZYME OF KETOGENESIS?
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HMG-CoA synthase (pg. 84)
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RATE DETERMINING ENZYME OF CHOLESTEROL SYNTHESIS?
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HMG-CoA reductase (pg. 84)
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WHAT PRODUCES 32 NET ATP? (WHAT SHUTTLE USED & ORGAN?)
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- Aerobic metabolism of glucose - Malate-aspartate shuttle - Heart & Liver (pg. 86)
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WHAT PRODUCES 30 NET ATP? (WHAT SHUTTLE USED & ORGAN?)
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Glycerol-3-phosphate shuttle Muscle (pg. 86)
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WHAT PRODUCES 2 NET ATP PER GLUCOSE MOLECULE?
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Anaerobic glycolysis (pg. 86)
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WHAT IS CARRIED IN ACTIVE FORM BY ATP?
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Phosphoryl groups (pg. 86)
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WHAT IS CARRIED IN ACTIVE FORM BY NADH,NADPH, AND FADH2 ?
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Electrons (pg. 86)
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WHAT IS CARRIED IN ACTIVE FORM BY CoA AND LIPOAMIDE?
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Acyl groups. (pg. 86)
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WHAT IS CARRIED IN ACTIVE FORM BY BIOTIN?
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CO2 (pg. 86)
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WHAT IS CARRIED IN ACTIVE FORM BY TETRAHYDROFOLATES?
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1-Carbon units (pg. 86)
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WHAT IS CARRIED IN ACTIVE FORM BY S-ADENOSYLMETHIONINE (SAM)?
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CH3 groups (pg. 86)
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WHAT IS CARRIED IN ACTIVE FORM BY TPP?
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Aldehydes. (pg. 86)
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HMP SHUNT PRODUCES WHAT ELECTRON?
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NADPH (pg. 86)
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WHAT 4 PROCESSES IS NADPH USED IN?
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- Anabolic processes - Respiratory processes - Cytochrome P-450 system - Glutathione reductase (pg. 86)
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WHAT TYPE OF PROCESS IS NAD+ USED IN?
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Catabolic processes (pg. 86)
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WHAT MAIN TYPE OF PROCESS IS NADPH USED IN?
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Anabolic processes. (pg. 86)
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WHAT DOES PHOSPHORYLATION OF GLUCOSE YEILD?
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Glucose-6-phosphate. (pg. 86)
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PHOSPHORYLATION REACTION IS CATALYZED BY WHAT? (2)
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Hexokinase & Glucokinase. (pg. 86)
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LOW GLUCOSE CONCENTRATIONS CAUSES WHAT TO SEQUESTER IN TISSUES?
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at low glucose concentrations Hexokinase sequesters GLUCOSE in the tissues. (pg. 86)
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WHAT HAPPENS DURING HIGH GLUCOSE SCENARIOS?
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Excess glucose stored in liver. (pg. 86)
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LOCATION OF HEXOKINASE
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Most tissues except liver and β cells of pancreas (pg. 86)
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LOCATION OF GLUCOKINASE
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Liver and β cells of pancreas (pg. 86)
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Km OF HEXOKINASE AND AFFINITY
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Lower (Increased affinity) (pg. 86)
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Km OF GLUCOKINASE AND AFFINITY
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Higher (Decreased affinity) (pg. 86)
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WHICH HEXOKINASE./GLUCOKINASE INDUCED BY INSULIN?
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Glucokinase affected by Insulin. (pg. 86)
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WHICH HEXOKINASE/GLUCOKINASE FEEDBACK INHIBITED BY GLUCOSE-6-PHOSPHATE?
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Hexokinase affected by Glucose-6-P (pg. 86)
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WHICH HEXOKINASE/GLUCOKINASE AFFECTED BY (MODY)
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Glucokinase. (pg. 86)
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GLUCOSE-6-P INHIBITS WHAT?
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Hexokinase (pg. 87)
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FRUCTOSE-6-P INHIBITS WHAT?
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Glucokinase (pg. 87)
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WHICH FUNCTIONS ARE REVERSED BY PHOSPHORYLATION OF PROTEIN KINASE A?
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FBPase-2/PFK-2 (pg. 87)
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COMPARE FASTING STATE PROCESSES AGAINST FED STATE PROCESSES: -Glucagon/Insulin -cAMP -Protein kinase A -PFK-2 -glycolysis -Gluconeogenesis
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Fasting State: - Increased glucagon - Increased cAMP - Increased protein kinase A - Increased FBPase 2 - Decreased PFK-2 - Less glycolysis - MORE gluconeogenesis Fed State: - Increased insulin - Decreased cAMP - Decreased protein kinase A - Decreased FBPase 2 - Increased PFK-2 - more glycolysis - LESS gluconeogeneis (pg. 87)
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WHAT IS RESPONSIBLE FOR LINKING GLYCOLYSIS AND TCA CYCLE?
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Mitochondrial enzyme complex. (pg. 87)
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5 COFACTORS OF PYRUVATE DEHYDROGENASE COMPLEX
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- Thiamine pyrophosphate (B1) - Lipoic acid - CoA (B5) - FAD (B2) - NAD (B3) (pg. 87)
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WHAT ACTIVATES PYRUVATE DEHYDROGENASE COMPLEX?
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- Increased NAD+/NADH ratio - Increased ADP - Increased Ca2+ (pg. 87)
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PYRUVATE DEHYDROGENASE IS SIMILAR TO WHAT OTHER COMPLEX?
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α-ketoglutarate dehydrogenase complex. (pg. 87)
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WHAT DOES α-KETOGLUTARATE DEHYDROGENASE COMPLEX CONVERT?
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α-ketoglutarate to succinyl-CoA (TCA cycle) (pg. 87)
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WHAT ARE SOME OF THE RESULTS OF ARSENIC REGARDING METABOLISM?
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- Arsenic causes glycolysis to produce zero net ATP - Arsenic inhibits lipoic acid. (pg. 87)
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WHAT DOES PYRUVATE DEHYDROGENASE COMPLEX DEFICIENCY CAUSE? INHERITANCE?
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- Causes a buildup of pyruvate that gets shunted to lactate via LDH and alanine via ALT. - X-linked recessive (pg. 88)
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WHAT ARE THE FINDINGS IN PYRUVATE DEHYDROGENASE COMPLEX DEFICIENCY?
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-Neurologic defects -Lactic Acidosis -Increased serum alanine (starting in infancy) (pg. 88)
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WHAT IS THE TREATMENT FOR PYRUVATE DEHYDROGENASE COMPLEX DEFICIENCY?
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-Increase intake of ketogenic nutrients -Increase lysine and leucine. (pg. 88)
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WHAT ARE THE 4 PATHWAYS OF PYRUVATE METABOLISM?
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1. Alanine aminotransferase (B6) 2. Pyruvate carboxylase (biotin) 3. Pyruvate dehydrogenase (B1/B2/B3/B5/Lipoic acid) 4. Lactic acid dehydrogenase (B3) (pg. 88)
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PLEASE DESCRIBE THE 4 FUNCTIONS OF PYRUVATE METABOLISM
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1. Alanine aminotransferase carries amino groups to liver from muscle 2. Pyruvate carboxylase where oxaloacetate can replenish TCA cycle or be used in gluconeogenesis. 3. Pyruvate dehydrogenase transition from glycolysis to TCA cycle 4. Lactic acid dehydrogenase is the end of anaerobic glycolysis. (pg. 88)
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LACTIC ACID DEHYDROGENASE IS THE MAJOR PATHWAY OF WHAT CELLS/TISSUES?
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- RBC'S - WBC'S - Kidney medulla - Lens - Testes - Cornea (pg. 88)
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TCA CYCLE PRODUCES 10 ATP/ACETYL-CoA (2x everything per glucose) HOW?
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- (3) NADH - (1) FADH2 - (2) CO2 - (1) GTP per acetyl-CoA (pg. 88)
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WHAT PART OF THE CELL DOES TCA CYCLE OCCUR?
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Mitochondria. (pg. 88)
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WHAT ARE THE 8 SUBSTRATES OF TCA CYCLE?
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- Citrate - Isocitrate - α-ketoglutarate - Succinyl CoA - Succinate - Fumarate - Malate - Oxaloacetate (pg. 88)
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NADH ELECTRONS FROM GLYCOLYSIS ENTER MITOCHONDRIA VIA WHAT 2 SHUTTLES?
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Via Malate-aspartate or glycerol-3-phosphate shuttle. (pg. 89)
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WHAT DRIVES PRODUCTION OF ATP IN REGARDS TO ELECTRON TRANSPORT CHAN/OXIDATIVE PHOSPHORYLATION?
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Formation of protein gradient, coupled to oxidative phosphorylation. (pg. 89)
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ATP PRODUCED VIA ATP SYNTHASE
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1 NADH --> 2.5 ATP 1 FADH2 --> 1.5 ATP
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WHAT DOES ELECTRON TRANSPORT INHIBITORS INHIBIT AND WHAT DOES THIS INHIBITION CAUSE?
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Directly inhibit electron transport causing decreased proton gradient and block of ATP synthesis. (pg. 89)
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WHAT DOES ATP SYNTHASE INHIBITORS INHIBIT AND WHAT DOES THIS INHIBITION CAUSE?
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Directly inhibits mitochondrial ATP synthase which causes a increase in proton gradient. No ATP produced since electron transport stopped. (pg. 89)
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WHAT DOES UNCOUPLING AGENTS CAUSE?
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Increased permeability of membrane causing a decreased proton gradient and Increased O2 consumption. ATP synthesis stopped Electron transport continues Produces HEAT. (pg. 89)
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HOW DOES ASPIRIN CAUSE FEVERS?
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Aspirin overdose can cause fever. (pg. 89)
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4 GLUCONEOGENEISIS IRREVERSIBLE ENZYMES
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- Pyruvate carboxylase - Phosphoenolpyruvate carboxykinase - Fructose-1,6-bisphosphatase - Glucose-6-phosphatase (pg. 89)
