1. Which of the following statements best describes properties of oxidative phosphorylation? A. B. C. D. E. 2. Electrons flow from least reduced to most reduced carriers. The rate of electron transport is controlled by the concentration of ADP. The transfer of electrons from FADH2 to NAD+ is thermodynamically favored. The transfer of electrons from the cytosol to the mitochondrion by the glycerol phosphate shuttle results in the synthesis of 3 ATPs. Treatment of mitochondria with 2,4-dinitrophenol leads to decreased transport of electrons from NADH to O2. In humans, glycogen and triglyceride are the major storage forms of carbohydrate and fatty acids, respectively. Which of the following statements regarding these energy stores are TRUE? 1) 2) 3) 4) 5) A. B. C. D. E. 3. Branching of glycogen increases its solubility. Triglyceride is synthesized from three fatty acids and one glyceraldehyde 3-phosphate. Rapid mobilization of fatty acids during a sprint enables preferential metabolism of this fuel compared to glycogen. Glycogenin initiates the synthesis of a new glycogen particle. In terms of the amount of energy made available per gram oxidized, triglyceride is a more efficient storage form than glycogen. 1, 2, 3 only 1, 2, 4 only 1, 4, 5 only 2, 3, 5 only 3, 4, 5 only In response to increased exercise and the consequent lowered energy charge in muscle which of the following changes does NOT occur? A. B. C. D. E. Lower ATP/ADP ratio stimulates oxidative phosphorylation and electron transport. Amino acid degradation is stimulated by increased NAD+/NADH ratio. Elevated acetyl CoA levels stimulate pyruvate carboxylase. Increased NAD+ and FAD levels stimulate fatty acid ß-oxidation. Lower ATP/ADP levels slow glutamate dehydrogenase. 1 4. Under conditions where terminal oxidation or tissue oxygen supply is limited in muscle glycolysis changes. Which of the following changes occurs in response to limited terminal oxidation or oxygen supply? 1) 2) 3) 4) A. B. C. D. E. 5. if 1, 2, 3 are correct if 1 and 3 are correct if 2 and 4 arc correct if only 4 is correct if all four are correct All of the following cofactors arc required in the oxidative decarboxylation of alpha-keto acids EXCEPT: A. B. C. D. E. 6. Pyruvate is reduced to lactate by NADH The rate of glycolysis slows down The rate of ATP production in the cytosol increases NADH oxidation by the electron transport system increases Biotin Lipoic acid Coenzyme A NAD+ Thiamine pyrophosphate Phosphofructokinase (PFK1) is the central regulatory enzyme for glycolysis. Which of the following conditions would bring about a decrease in the activity of PFK1 in the liver? 1) 2) 3) 4) A. B. C. D. E. Elevated levels of AMP Elevated concentrations of citrate Elevated levels of fructose 2,6-bisphosphate (F26BP) Elevated levels of ATP if 1, 2, 3 are correct if 1 and 3 are correct if 2 and 4 are correct if only 4 is correct if all four are correct 2 7. Which of the following statements about fatty acid ß-oxidation is TRUE? A. B. C. D. E. 8. Obesity in the United States has reached epidemic levels. Which one of the following statements regarding obesity is FALSE? A. B. C. D. 9. Mitochondrial metabolism of unsaturated even-chain fatty acids yield less ATP than saturated even-chain fatty acids of equal chain length. NAD+ and FMN are required electron acceptors for the two oxidation steps. Acyl carrier protein is required for attachment to the fatty acid before ß-oxidation can begin. ß-oxidation is localized in the cytosol, taking advantage of the elevated NAD+ present. Malonyl CoA stimulates ß -oxidation. Obesity is strongly associated with uncontrolled Type I diabetes mellitus. Obesity could arise through mutation of the leptin gene. Obesity is one component of the Metabolic Syndrome. Obesity occurs when caloric intake exceeds energy expenditure. The pathways of fatty acid synthesis and degradation differ markedly. Which one of the following statements is FALSE? A. B. C. D. E. Fatty acid synthesis occurs within the cytosol, while fatty acid degradation occurs within the mitochondrial matrix. Three carbon units are added as malonyl-CoA in fatty acid synthesis, while two carbon units are liberated as acetyl-CoA in fatty acid degradation. NADPH is the electron donor in fatty acid synthesis, while FAD and NAD+ are electron acceptors in fatty acid degradation. CO2/HCO3 is required in fatty acid synthesis, but is not liberated in the oxidation pathway. Fatty acid synthesis occurs mainly in the liver and adipose, while fatty acid degradation is more widely distributed. 3 10. A young boy (9) with no previous history of heart disease was admitted to the hospital with clinical signs of severe heart failure. The parents informed the doctor that their son had not eaten for the last two days, due to a mild infection. Blood glucose and ketone body levels were found to be abnormally low, while circulating non-esterified fatty acids were greatly elevated. An abnormality in which one of the following enzymes is most consistent with this case? A. B. C. D. E. 11. Which one of the following statements concerning regulation of metabolic pathways is LEAST likely to be TRUE? A. B. C. D. E. 12. ß-ketoacyl-CoA transferase Hormone-sensitive lipase Liver glycogen phosphorylase Carnitine Acyltransferase I Lipoprotein lipase Reversible, near-equilibrium enzyme-catalyzed reactions arc normally key regulatory sites for opposing metabolic pathways. The level of gene expression of a regulatory enzyme often influences the flux of carbon through its metabolic pathway. Substrate availability affects the rate of enzymatic reactions. Allosteric effectors modulate the activity of enzymes by binding to sites on the protein that are distinct from the active site. Phosphorylation is a common form of reversible covalent modification that often activates or inhibits enzymatic activity. The mitochondrion is an highly ordered structure whose integrity is critical to its function. Which of the following statements is UNTRUE? A. B. C. D. E. Components of the electron transport chain are bound to or associated with the inner membrane of the mitochondrion. The inner-membrane of the mitochondrion provides the permeability barriers of the mitochondrion. The formation of ATP in the mitochondrion depends on a H+ gradient in which the concentration of hydrogen ion is higher inside the mitochondrion than it is in the intermembrane space. The inner membrane contains transporters responsible for cross-membrane passage of certain substrates and ions. Most enzyme components of the citric acid cycle arc localized in the mitochondrial matrix. 4 13. Flux through many metabolic pathways is regulated at the level of gene expression. Which of the following proteins would be expected to be induced in skeletal muscle during starvation? 1) 2) 3) 4) 5) A. B. C. D. E. 14. 1, 2, 3 only 1, 2, 4 only 1, 4, 5 only 2, 3, 5 only 3, 4, 5 only Gluconeogenesis and glycolysis are opposing metabolic pathways. Which one of the following metabolite changes INCREASES net flux of carbon through the glycolytic pathway in the liver following ingestion of a high caloric diet? A. B. C. D. E. 15. Components of the proteosome Carnitine acyltransferase I Glucose 6-phosphatase Aspartate aminotransferase Glycerol kinase Increased ATP levels Decreased fructose 2,6-bisphosphate levels Increased citrate levels Increased alanine levels Increased fructose 1,6-bisphosphate levels Which one of the following is LEAST likely to promote fatty acid synthesis? A. B. C. D. E. Carbohydrate-rich meal Induction of glucokinase Increased hepatic fructose 2,6-bisphosphate levels Increased phosphorylation of pyruvate kinase Dephosphorylation of pyruvate dehydrogenase 5 16. Amino acid transaminases participate in the removal of ammonia equivalents from amino acids. Which of the following statements about amino acid transaminases is INCORRECT? A. B. C. D. E. 17. A teenage child is presented to a doctor with an abnormally low body mass index (BMI). The family is concerned that, despite efforts to increase weight gain through increased calorie intake, their child remains abnormally thin. Body composition scans show markedly lower levels of fat deposition, with a normal lean body mass. Tracer studies show accelerated rates of fatty acid oxidation, with rates of endogenous fatty acid synthesis within a normal range. Which one of the following would be most consistent with the altered metabolism observed in this patient? A. B. C. D. E. 18. Transaminases require pyridoxal phosphate as a cofactor. Transaminases utilize α-ketoglutarate as an amino acceptor. Transaminases form a Schiff base between the pyridoxal phosphate cofactor and their substrates. Transaminases catalyze the elimination of free ammonia. Transaminases are freely reversible. Abnormality in muscle acetyl-CoA carboxylase Abnormality in thiokinase Abnormality in fatty acid synthase Deficiency in carnitine Deficiency in biotin Which one of the following is LEAST likely to occur during uncontrolled Type 1 diabetes mellitus? A. B. C. D. E. Increased hepatic glucose production. Increased skeletal muscle protein synthesis. Increased adipose lipolysis. Increased skeletal muscle fatty acid oxidation Decreased skeletal muscle glucose oxidation 6 19. Which of the following statements regarding energy storage and mobilization in healthy humans is TRUE? A. B. C. D. E. 20. Which of the following statements about the urea cycle is INCORRECT? A. B. C. D. E. 21. Long-chain fatty acyl groups ATP Citrulline NAD+ Pyruvate Which of the following statements is INCORRECT about glutamate dehydrogenase? A. B. C. D. E. 23. Each turn of the urea cycle results in the elimination of 2 NH4+ equivalents. The urea cycle requires 4 high energy phosphate equivalents. Ornithine serves as an amino donor. The urea cycle generates fumarate in a net fashion. The urea cycle requires the participation of aspartate. Membrane barriers restrict passage of metabolic intermediates and ions from one subcellular compartments to another except through transporter mediated processes. Which of the following compounds is not transported across the mitochondrial membrane by a transporter? A. B. C. D. E. 22. Due to the large muscle mass, more kcal of energy is available from mobilizable muscle protein than from adipose tissue triglycerides or liver glycogen. All of the steps that use or generate ATP are catalyzed by different enzymes in glycolysis as compared to gluconeogenesis. The glycolytic pathway includes intermediates that have 4 carbon atoms. Fructose 2,6-bisphosphate functions primarily to regulate glycogen synthesis and breakdown. Pyruvate must be converted to a TCA cycle intermediate before its carbons can be used for gluconeogenesis. It is drawn to product formation by removal of NADH by the electron transfer chain. It is inhibited by GTP. It is drawn to product formation by NH3 removal by the urea cycle. It is located in the mitochondrion. It removes α-ketoglutarate from the mitochondrial pool. The citric acid cycle begins with the condensation of oxaloacetate with acetyl CoA. What is the correct sequence of steps following that condensation? A. B. Citrate → α-ketoglutarate → malate → isocitrate → fumarate → succinyl CoA succinate → oxaloacetate Citrate → malate → succinate → α-ketoglutarate → isocitrate → succinyl CoA 7 C. D. 24. All of the following properties make glycogen an ideal energy source for contracting skeletal muscle EXCEPT: A. B. C. D. E. 25. Glycogen can be rapidly degraded in response to changes in the energetic status of the cell. At the time of exercise, anaerobic glycolysis of a glycogen-derived glucosyl unit generates one extra net ATP, compared to free glucose. The branched structure of glycogen increases the number of sites for glycogen phosphorylase to act. Association of glycogen with the enzymes involved in its metabolism facilitates rapid mobilization. Dissociation of glycogenin from the glycogen particle during contraction prevents glycogen synthesis. Which of the following statements about the ß-oxidation of odd chain, short chain or unsaturated fatty acids and ketone bodies is INCORRECT? A. B. C. D. E. 26. → fumarate → oxaloacetate Citrate → isocitrate → α -ketoglutarate → succinyl CoA → succinate → malate → fumarate → oxaloacetate Citrate → isocitrate → α -ketoglutarate → succinyl CoA → succinate → fumarate → malate → oxaloacetate Odd chain fatty acid ß-oxidation yields a molecule of propionyl CoA which is carboxylated and rearranged to succinyl CoA. Acetoacetic acid can be activated by interaction with succinyl CoA. Poly unsaturated fatty acids may require reduction of a double bond by an NADH dependent reductase. The ß-oxidation of oleic acid (18 carbons, 1 unsaturated bond) produces 2 ATP equivalents less than its saturated 18 carbon cognate stearic acid. Full ATP yield from fatty acids undergoing ß-oxidation requires a functional citric acid cycle and a functional coupled electron transport chain. In addition to glucose, galactose and fructose can be metabolized to generate energy in the form of ATP. Which of the following statements about the metabolism of galactose and fructose is UNTRUE? A. Fructose and galactose are phosphorylated by special kinases as the major pathways. 8 B. C. D. E. 27. All of the following statements regarding the amino acid glutamine are correct EXCEPT? A. B. C. D. E. 28. Rapidly dividing cells, such as lymphocytes, prefer it as a nutrient. It is an inter-organ carrier of nitrogen during conditions such as starvation. It is important for maintaining whole body acid-base balance. Its alpha-amino group can be removed by glutamine dehydrogenase. It is a glucogenic amino acid. Both liver and pancreas take advantage of the unique properties of GLUT2 and glucokinase, allowing rapid response of these organs to changes in blood glucose levels. Which one of the following statements regarding GLUT2 and glucokinase in the organs is FALSE? A. B. C. D. E. 29. Fructose 1-phosphate is cleaved by a special aldolase which generates dihydroxy acetone phosphate and glyceraldehyde. The hereditary absence of fructokinase causes a disabling disease due to the accumulation of fructose 1-phosphate. Hereditary absence of galactose 1-P uridyltransferase leads to the accumulation of galactitol and galactose 1-phosphate. Galactose can be reduced to galactitol by aldolase reductase and can lead to cataracts in the lens of the eye. GLUT2 permanently resides at the cell surface. GLUT2 allows either import or export of glucose, depending upon blood glucose levels. Glucokinase is not inhibited by glucose 6-phosphate. Glucokinase has a higher affinity for glucose than hexokinase. Glucokinase is induced in the liver following a carbohydrate rich-meal. Metabolite levels can change very rapidly within the hepatocyte, depending upon substrate availability and hormonal stimulation. Metabolites can alter the activities of specific enzymes. Which of the following metabolic-enzyme interactions would INCREASE fatty acid synthesis from glucose? 1) 2) 3) Pyruvate and pyruvate dehydrogenase kinase Citrate and acetyl-CoA carboxylase 1 Fructose 2,6-bisphosphate and fructose 1,6-bisphosphatase 9 4) A. B. C. D. E. 30. Type I diabetes mellitus is more prevalent than Type II diabetes mellitus. Type II diabetes mellitus is usually an autoimmune disease. Ketoacidosis is more common in Type I compared to Type II, diabetes mellitus. Insulin resistance is often an underlying cause of Type I diabetes mellitus. Which of the following conditions would slow the rate of ß-oxidation? A. B. C. D. E. 32. if 1, 2, 3 are correct if 1 and 3 are correct if 2 and 4 are correct if only 4 is correct if all 4 are correct The two most common forms of diabetes mellitus are Type I and II. Which one of the following statements most accurately describes a characteristic of diabetes mellitus? A. B. C. D. 31. Fructose 1,6-bisphosphate and pyruvate kinase ↑ (NAD+] ↓ [HSCoA) ↑ [FMN] ↓ [Malonyl CoA] ↓ [Citrate] AMP is as much a signaling molecule in skeletal muscle as cAMP. Which one of the following statements concerning AMP is FALSE in skeletal muscle? A. B. C. AMP levels increase during muscular contraction via the adenylate kinase reaction. AMP increases fatty acid oxidation by affecting the activity of acetyl-CoA carboxylase 2. AMP increases glycogen breakdown by allosterically activating glycogen phosphorylase. 10 D. E. 33. Acetyl-CoA carboxylase (ACC) is important not only for fatty acid synthesis, but also for regulation of fatty acid ß-oxidation. Which one of the following statements regarding ACC is TRUE? A. B. C. D. E. 34. It requires vitamin B6 (pyridoxal phosphate) It is more active when phosphorylated It is allosterically activated by pyruvate It is allosterically inhibited by fatty acyl-CoA It is located within the mitochondrial matrix One of the many pathways of protein degradation is the ubiquitin/proteasome pathway. Which one of the following statements regarding this pathway is TRUE? A. B. C. D. E. 35. AMP increases glycolytic flux by allosterically activating phosphofructokinase. AMP returns to baseline levels after muscular contraction via the phosphodiesterase reaction. The E1 protein confers specificity of protein targeting for degradation. Following ubiquitinization, the tagged protein enters the lysosome. Ubiquitin is degraded along with the tagged protein. Ubiquitin is covalently bound to lysine side chains on target proteins. The proteasome core region is important for recognizing the ubiquitin tag on targeted proteins. Lipolysis would tend to be accelerated under which of the following conditions? 1) 2) 3) 4) 5) A. B. Uncontrolled type I diabetes Overnight fast Eating a high carbohydrate/low fat meal Chronic stress or infection Exercise 1,2,3,4 only 1,2,3,5 only 11 C. D. E. 36. Ketone bodies can be considered as water soluble, inter-organ transferable forms of acetyl-CoA. Which one of the following statements regarding ketone bodies is TRUE? A. B. C. D. E. 37. More ATP are generated by the full oxidation of acetoacetate compared to hydroxybutyrate. Acetoacetate, ß-hydroxybutyrate and acetone are all important sources of energy for skeletal muscle during starvation. Inhibition of ketone body synthesis would not be expected to have a significant impact on glucose homeostasis during starvation. Skeletal muscle is unable to oxidize ketone bodies. Increased lipolysis is a major influence driving increased rates of ketone body synthesis during fasting. The hydrolysis of ATP often drives the phosphorylation of other compounds such as glucose 6-phosphate. The ∆G°' of hydrolysis of ATP is -7.3 kcal/mol while the ∆G°' of hydrolysis of glucose 6-phosphate is -3.3 kcal/mol. What is the ∆G°' for the phosphorylation of glucose by ATP? A. B. C. D. E. 38. 1,2,4,5 only 2,3,4,5 only All five - 0.6 + 10.6 - 4.0 + 4.0 - 5.3 A 2-month-old boy is evaluated for failure to thrive. As the pediatrician is examining the patient, she witnesses a seizure. Physical examination reveals an enlarged liver. Serum chemistries demonstrate severe hypoglycemia (low blood glucose), hyperlipidemia (high blood lipids), lactic acidosis and ketosis. A defect in which of the following enzymes best accounts for these findings? A. B. C. D. E. Liver glycogen phosphorylase Liver glucose 6-phosphate dehydrogenase Liver glucose 6-phosphatase Muscle glycogen phosphorylase Liver phosphofructokinase 2 12 39. A patient has a hereditary disorder characterized by a grossly abnormal electroencephatogram (EEG) and increased blood ammonium ion concentration. The most likely cause is a deficiency of which of the following enzymes? A. B. C. D. E. 40. The concentration of the enzymes of glycolytis, citric acid cycle and electron transport chain vary among the various tissues of the body. Which of the following statements if INCORRECT? A. B. C. D. E. 41. Asparagine synthetase Carbamoyl phosphate synthetase I Fumarase Glutamate-oxaloacetate transaminase Glutaminase Red blood cells rely completely on glycolysis for ATP generation. Skeletal muscle has high levels of glycolytic enzymes. Pyruvate kinase deficiency in red blood cells causes low ATP levels in the erythrocytes. Brain uses fatty acids preferentially to meet its energy needs. Glucose 6-phosphate dehydrogenase deficiency in red blood cells can enable hemolysis upon exposure to sulfa drugs. Defects in amino acid metabolism lead to specific disease conditions. Which of the following statements is INCORRECT? A. B. C. D. Phenylketonuria is caused by a deficit in one or more of the enzymes involved in catalyzing the hydroxylation of phenylalanine to tyrosine. Alkaptonuria is caused by a defect in homogentisic acid oxidase. A deficiency in vitamin B12 can result in a build-up of breakdown products of valine and isoleucine. Maple syrup urine disease is caused by a deficiency of branched chain amino acid transaminase. 13 42. The pentose phosphate pathway offers a source of pentoses and NADPH for metabolism as well as an entry for dietary pentoses into metabolism. Which of the following statements is UNTRUE? A. B. C. D. E. 43. Insulin has opposing effects on glycogen synthesis and degradation, many of which are mediated by protein phosphatase 1 (PP1) activation. Which one of the following statements regarding PP1-mediated regulation of glycogen metabolism in skeletal muscle is FALSE? PP1: A. B. C. D. E. 44. NAD+ HSCoA GTP FAD ADP Insulin acts on the adipocyte to promote triglyceride storage by all of the following mechanisms EXCEPT: A. B. C. D. E. 46. Inactivates inhibitor 1. Activates adenylate cyclase Activates glycogen synthase. Inactivates phosphorylase kinase. Inactivates glycogen phosphorylase. An elevation of the concentrations of which of the following would result in a decreased rate at which acetyl CoA is converted to CO2? A. B. C. D. E. 45. The transketolase and transaldolase reactions are readily reversible. Pentoses enter the glycolytic pathway as glyceraldehyde 3-phosphate and fructose 6-phosphate. The transketolase enzyme requires thiamine pyrophosphate as cofactor. Glucose 6-phosphate dehydrogenase is inhibited by a low NADP+/NADPH ratio. Glucose 6-phosphate dehydrogenase is stimulated by long chain fatty acyl CoA. Increased lipoprotein lipase activity associated with the adipocyte Increased glucose uptake into the adipocyte Induction of glycerol kinase gene expression by the adipocyte Induction of fatty acid synthase gene expression by the adipocyte Dephosphorylation of hormone sensitive lipase within the adipocyte A certain biological reaction starts with substrate and passes through intermediate products T and V before arriving at the final product X. The reaction sequence and the ∆G° for each conversion are given below. 14 +1.6 -7.5 +5.5 S→T→V→X From this information which of the following statements is accurate? A. B. C. D. E. 47. Which of the following is an exclusively ketogenic amino acid? A. B. C. D. E. 48. Under standard conditions the reaction will go from S to X Under standard conditions the reaction will go from X to S The conversion with the fastest rate is the conversion from T to V The rate limiting step is the first step The reaction is unlikely to reach equilibrium Aspartate Trytophan Leucine Isoleucine Phenylalanine Hepatic fatty acid metabolism and gluconeogenesis are tightly coupled. Which one of the following statements regarding the interplay between ß-oxidation and gluconeogenesis is FALSE? A. B. C. D. E. Acetyl-CoA stimulates gluconeogenesis by allosterically activating phosphoenolpyruvate carboxykinase. Fatty acid oxidation drives gluconeogenesis by generating NADH and ATP (via oxidative phosphorylation). Odd chain fatty acids can provide carbon atoms for net glucose synthesis. Acetyl-CoA is utilized in ketogenesis, freeing CoA for continued ß-oxidation. Rates of both hepatic oxidation and gluconeogenesis are increased in uncontrolled type I diabetes. 15 49. Skeletal muscle pyruvate dehydrogenase serves as the entry for pyruvate to metabolism by the citric acid cycle. Which of the following slows pyruvate dehydrogenase activity? A. B. C. D. E. 50. Elevated levels of NAD+ acceptor. Low ratios of acetyl CoA/HSCoA. Effects of rising levels of GTP on pyruvate dehydrogenase. Ca++ effects on pyruvate dehydrogenase phosphatase. Allosteric effects of pyruvate on pyruvate dehydrogenase kinase. Aerobic glycolysis is carried out in muscle accounting for the entry of carbohydrates into the energy generative process. Which of the following statements about aerobic glycolysis is INCORRECT? A. B. C. D. E. Glycolysis is localized in the cytosol of the cell. Skeletal muscle pyruvate kinase is inactivated by phosphorylation. NAD+ is regenerated through the electron transport chain. ATP is foamed by substrate-level phosphorylation in glycolysis. ADP is a required phosphorylation acceptor for glycolysis. 16 Medical School Biochemistry Course EXAM ANSWER KEY Block II Q# 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 V1 B C E B A C A A B D A C B E D D A B E C D E D E C C D D E C B E D D C E C C B D D E B C C A C A C B V2 B A C C B D B E C D C C B E A C E E A D D D D B C C E C B D E B E A C E B D C D C D B A A C A D C E 17 V3 B E D E D B B C C E A C C A D C B B D D A E B C C E A E D C B D B C D D C D B C E A E A C E C C D A V4 C C A E D C B E A D C C B B E B B E C A C D A D A D E C D C C A A D C D C D B B E E C B E D C E D B 18