BMB 514 -- Final Exam -- October 20, 2003


Tear off and keep this for your record of your answers.


ANSWER GRID


Version of the Exam: 1A




BMB 514 -- Final Exam -- October 20, 2003 Name ___________________________

BEFORE you begin the exam, please complete the following information on your response sheet:
(a) your name and signature (b) your student number (PID)
(c) your college -- in the area under SECTION: mark 001 for CHM student
mark 002 for COM student
(d) your version of the exam is 1A -- mark this in the area under FORM
• There are 60 questions on this exam. For each question, mark the letter corresponding to what you consider is the BEST answer on the response sheet provided. • When you leave the exam room, please turn in your RESPONSE SHEET and your EXAM to the proctors standing by the back doors INSIDE the auditorium. Once you exit the auditorium, please DO NOT return until we have reopened the doors (~9:45 a.m.).
• There will be answer keys to this exam outside A-133 Life Sciences after the exam is completed. You may wish to copy your responses from the response sheet onto the answer grid on the first page of this exam so that you can check your results. You can tear off the first page and take it with you.
• You have 2 hours to complete this exam. We will close the exam promptly at 9:30 a.m.
• Do well and good luck.
Questions 1-3 refer to the description below.
Three of your patients have previously suffered from symptoms of Gout. All of these patients have followed a restricted diet to maintain "normal" values for serum uric acid (3-7 mg/dL), as well as urinary uric acid level (below the solubility limit of ~15 mg/dL). In the hypothetical cases described in questions 1-3, each of the three patients has a somewhat different underlying cause and you are asked to predict the laboratory findings on serum uric acid and urinary uric acid levels when the patient's problem flares up.


1. The patient is diabetic and has gone into ketoacidosis.


2. The patient has a hereditary hyperactive PRPP (5-phosphoribosyl-1-pyrophosphate) amidotransferase.


3. The patient has a form of Lesch-Nyhan syndrome, in which the HGPRT (hypoxanthine-guanine phosphoribosyl transferase) exhibits low activity (10-20% of normal).


4. Which of the following is an inhibitor of the enzyme dihydrofolate reductase?

A. allopurinol
B. methotrexate
C. deoxyadenosine triphosphate
D. 5-fluorouracil
E. N5-methyl tetrahydrofolate


5. Biotin is a cofactor in the transfer of one carbon units at which oxidation level?
A. -CH3
B. -CH2-
C. =CH-
D. -CH=O
E. -CO2
Questions 6 and 7
The flow chart below represents a summary of the pathways of 1-carbon metabolism. For example, a specific carbon atom on the amino acid serine can be moved until it ends up as a carbon atom on the membrane phospholipid phosphatidylcholine. For questions 6 and 7, identify the compound that matches the position of the question shown on the flow chart.

Abbreviations:
THF = tetrahydrofolate
SAHC = S-adenosylhomocysteine
R-NH2 = phosphatidylethanolamine
R-NH-CH3 = phsophatidylcholine
A. CH3-B12
B. dihydrofolate
C. Cysteine
D. Glutamine
E. S-adenosylmethionine
6. Find the position of this question in the flow chart and identify the compound.

7. Find the position of this question in the flow chart and identify the compound.

8. The direct product of the committed step of the de novo pyrimidine nucleotide synthesis pathway is:
A. bicarbonate
B. carbamoyl phosphate (cabamyl phosphate)
C. orotate
D. orotate monophosphate
E. uridine monophosphate
For questions 9-11, choose from the nucleotides whose structures are shown below. You might find it helpful if you identify each compound by its name before attmepting to answer the questions.

9. Which of the nucleotides shown above inhibits the committed step of de novo synthesis of purine nucleotides catalyzed by PRPP amidotransferase?

10. Which of the nucleotides shown above stimulates the activity of ribonucleotide reductase, which is responsible for converting ribonucleotides into their deoxy counterparts?

11. Which of the nucleotides shown above is the direct product of thymidylate synthase?


12. Adaptation to high altitudes results in an increase in the concentration of 2,3- diphosphoglycerate (DPG) from ~5 mM to ~8 mM inisde the red blood cells. What effect will the higher level of DPG have on the O2 binding affinity of hemoglobin in the red blood cells?
A. Both P50 and O2 binding affinity decrease.
B. Both P50 and O2 binding affinity increase.
C. P50 decreases and O2 binding affinity increases.
D. P50 increases and O2 binding affinity decreases.
E. Both P50 and O2 binding affinity remain the same.
13. The isohydric transport of CO2:
A. is dependent on the buffering capacity of hemoglobin.
B. takes advantage of the low pO2 in the red blood cell.
C. causes a drastic fluctuation of pH in the plasma.
D. does not involve the formation of cabamino hemoglobin.
E. requires the same directional movement of chloride and bicarbonate anions.
Questions 14-16 refer to the case below.
A 3-year old child was brought to the hospital with a cough, respiratory distress, and cyanosis (bluish skin). Physical examination suggested a lower respiratory tract infection. Other laboratory data available:
 
Patient
Normal
  
[HCO3-] (mM)
pO2 (mm Hg)
pCO2 (mm Hg)
pH
  
?
30
90
7.1
23-25
80-100
35-45
7.35-7.45
 
Other useful values:
(a) pKa of carbonic acid, 6.1;
(b) solubility coefficient for CO2 at 37 oC, 0.03 mM/mm Hg
(c) log 10n = n
14. What is the plasma bicarbonate concentration?
A. 24 mM
B. 27 mM
C. 40 mM
D. 22 mM
E. 9 mM
15. Which of the following gives the best description of the acid-base status of the patient?
A. Acid-base normalcy
B. Respiratory acidosis
C. Respiratory alkalosis
D. Metabolic acidosis
E. Metabolic alkalosis
16. Which of the following represents a sign that the patient's body has initiated an attempt at compensation?
A. The pH value dropping below normal.
B. The pCO2 value rising above normal.
C. The skin turning bluish.
D. The pO2 value dropping below normal.
E. The bicarbonate concentration rising above normal.
Questions 17 and 18 refer to the figure below. The solid line shows the dependence of enzyme rate v (mmol/min) as a function of substrate concentraion S (mM). Also shown (dotted line) is the dependence of the rate in the presence of an inhibitor, present at a concentration of 2 mM.

17. The Vmax of the enzyme is:
A. 0.25 mmol/min
B. 0.5 mmol/min
C. 1 mmol/min
D. 2 mmol/min
E. 4 mmol/min
18. From the data provided in the graph, you can deduce that:
A. The inhibitor is a competitive inhibitor.
B. The enzyme failed to obey Michaelis-Menten kinetics.
C. The inhibitor in a non-competitive inhibitor.
D. The inhibitor changed the Vmax value of the enzyme.
E. The enzyme catalyzes the committed step of a reaction pathway.
19. Diabetes and the Atkins diet force the body to seek alternatives to glucose for energy. Which of the following is NOT a consequence of glucose deprivation?
A. Mobilization of fat stores
B. A decrease in gluconeogenesis activity
C. Increased production of ketone bodies
D. Increase in beta oxidation
E. Activation of hormone sensitive lipase
20. von Gierke's disease is characterized by a deficiency in glucose-6-phosphatase. One complication of von Gierke's disease is an increased risk of gout. This complication is primarily due to increased intracellular concentration of glucose-6-phosphate and increased production of nucleotides. What metabolic pathway can use glucose-6-phosphate to drive the overproduction of nucleotides?
A. Gluconeogenesis
B. Glycolysis
C. Pentose phosphate pathway
D. TCA cycle
E. Electron transport chain
21. What are the enzymes that catalyze the three regulated steps of glycolysis?
A. glyceraldehyde-3-phosphate dehydrogenase, phosphofructokinase, pyruvate kinase
B. hexokinase, phosphofructokinase, pyruvate kinase
C. fructose-1,6-bisphosphatase, hexokinase, phosphofructokinase
D. hexokinase, glyceraldehyde-3-phosphate dehydrogenase, phosphofructokinase
E. phosphoglycerate kinase, hexokinase, phosphofructokinase
22. The production of heat in brown adipose tissue is carried out by the thermogenin protein. Thermogenin produces heat by what mechanism?
A. uncoupling of the electron transport chain from ATP synthase (complex V)
B. Storing excess NADH to drive the electron transport chain
C. Increasing the activity of Complex I of the electron transport chain
D. Increasing the membrane potential of the inner mitochondrial membrane
E. Promoting the use of fatty acid oxidation in a well fed state
23. Which of the following correctly describes the reaction of the TCA cycle that is catalyzed by citrate synthase?
A. Regulated by oxaloacaetate
B. Produces a precursor for fatty acid synthesis
C. Regulated by succinyl-CoA
D. A and B
E. All of the above
24. Pompe's disease affects all organs and is characterized by a deficiency in a-1,4-glucosidase. In a patient with Pompe's disease, which of the following would best describe their glycogen stores?
A. decreased amount, normal branches
B. increased amount, excessive branching
C. decreased amount, absence of branching
D. increased amount, absence of branching
E. increased amount, normal branching
25. Thiamine deficiency can lead to Beri-Beri and Wenicke-Korsakoff syndrome. Which of the following lists enzymes that are directly affected by a thiamine deficiency?
A. pyruvate dehydrogenase, isocitrate dehydrogenase, transaldolase
B. a-ketoglutarate dehydrogenase, pyruvate dehydrogenase, transketolase
C. isocitrate dehydrogenase, a-ketoglutarate dehydrogenase, pyruvate dehydrogenase
D. transaldolase, transketolase, pyruvate dehydrogenase
E. malate dehydrogenase, a-ketoglutarate dehydrogenase, pyruvate dehydrogenase
26. Which of the following best describes phosphoenolpyruvate carboxykinase (PEPCK)?
A. catalyzes the conversion of oxaloacetate to phosphoenolpyruvate
B. is located in the cytosol
C. is negatively regulated by glucagon
D. A and B
E. all of the above
27. The reciprocal regulation of glycogen synthesis and breakdown is primarily controlled by which of the following?
A. hormonal regulation of adenylate cyclase and biological amplification
B. glucagon mediated inhibition of phosphorylase kinase and subsequent activation of glycogen synthase
C. cAMP mediated regulation of kinases that lead to the activation of glycogen phosphorylase and glycogen synthase
D. A and C
E. All of the above
28. Lipid breakdown (lipolysis) is stimulated when
A. glucagon levels are low.
B. insulin levels are high.
C. carbohydrate intake in the diet is low.
D. protein intake in the diet is low.
E. All of the above.
29. A patient is suffering from type 1 diabetes. She takes an overdose of insulin, resulting in which of the following effects in the liver?
A. Increased activity of glycogen phosphorylase.
B. Increased activity of fructose-2,6-bis phosphatase.
C. Increased activity of pyruvate dehydrogenase.
D. Decreased activity of fatty acyl transferase.
E. Decreased activity of HMG CoA reductase.
30. Fatty acid oxidation (b-oxidation) can, under certain conditions, lead to formation of ketone bodies. When and where would that occur?
A. In muscle during strenuous exercise.
B. In the heart, during a heart attack.
C. In adipose tissues when stimulated by high insulin.
D. In the liver when it is also carrying out gluconeogenesis.
E. In the red blood cell under oxidative stress.
31. An elderly patient with type 2 diabetes is found alone in her apartment in a coma. There is evidence that she has forgotten to take her medication and had low fluid intake. She would likely have
A. hyperosmolar hyperglycemia.
B. high levels of ketone bodies resulting in severe ketoacidosis.
C. very low blood sugar and hyperammonemia.
D. A and B are equal likely.
32. The condition known as Marasmus is caused by lack of adequate protein in the diet even though caloric intake from carbohydrates is sufficient. The following symptoms would be expected EXCEPT
A. edema, due to serum albumin breakdown
B. muscle wasting
C. fat deposition
D. increased gluconeogenesis in the liver

33. The normal pathway for breakdown of amino acids in the liver involves all the following enzymes EXCEPT
A. aminotransferases (transaminases)
B. glutamate dehydrogenase
C. carbamoyl phosphate synthetase
D. arginase
E. a ketoglutarate dehydrogenase
34. The enzyme glutamine synthetase is particularly important
A. in peripheral tissue to fix nitrogen for transport to the liver.
B. in the liver for release of ammonia to feed into the urea cycle.
C. in the muscle, to provide carbon skeletons for energy.
D. in the kidney to release ammonia into the urine.
35. If blood urea nitrogen (BUN) is high, this is most likely to be diagnostic of
A. liver dysfunction.
B. a heart attack.
C. strenuous exercise.
D. kidney dysfunction.
E. a stroke.
36. Lack of one essential amino acid will eventually be fatal because
A. all essential amino acids are required to allow nucleotide and porphyrin synthesis to proceed.
B. lack of essential amino acids causes severe energy deprivation in the brain.
C. lack of one essential amino acid will lead to high blood levels of ammonia, resulting in coma and death.
D. the synthesis of most proteins require all 20 amino acids; if one is missing, synthesis cannot proceed.
37. After five weeks of starvation, the levels of circulating fuels in the blood would be correctly described by all the following EXCEPT
A. glucose levels are about half those in the well-fed state.
B. ketone body levels are much higher than normal.
C. amino acid and lactate levels are higher than normal.
D. fatty acid levels (bound to albumin) are higher than normal.
E. b OH butyrate levels are much higher than normal.
38. Preproinsulin
A. is a member of the class of hormones known as amino acid derivatives.
B. is larger than insulin because it has a leader sequence plus an additional "C-peptide" component.
C. is secreted by the a-cells of the pancreas.
D. is the form of insulin that is stored in the pancreas.
E. when fully activated and released and bound to its receptor, it stimulates a chain of reactions within the cell that start with dephosphorylation of the insulin receptor.
39. Epinephrine acts on both muscle and liver and alters metabolism by:
A. inhibiting glycolysis in both
B. stimulating glycolysis in both
C. inhibiting glycolysis in muscle; stimulating it in liver
D. stimulating glycolysis in muscle; inhibiting it in liver
40. Glucose-6-phosphate is a key intermediate in metabolism. It is a direct substrate or product of all the following enzymes in liver EXCEPT
A. glycogen synthase
B. glucose-6-P dehydrogenase
C. phosphoglucose isomerase
D. hexokinase
E. glucokinase
41. Under starvation conditions, acetyl CoA produced by b-oxidation in the liver will largely be
A. converted to citrate.
B. used to make cholesterol.
C. converted to pyruvate by reversal of pyruvate dehydrogenase.
D. converted to oxaloacetate and then to glucose.
E. converted to acetoacetate and bOH butyrate
42. You switch from a high carbohydrate to a low carbohydrate diet. Within hours or days, the levels of metabolic enzymes will be altered to adjust to your new diet. The mechanism and nature of the change would NOT involve
A. ATP-dependent protease activity.
B. ATP-dependent ubiquitination of enzymes.
C. increased levels of phosphofructokinase (PFK).
D. increased levels of fructose-1,6 bisphosphatase (FBP)
E. decreased levels of HMG CoA reductase.
43. A patient has a defect leading to low activity of the acyltransferase enzyme involved in synthesis of fat and phospholipid. Which of the intermediates in the path would be most likely to accumulate:
A. diacylglycerol phosphate
B. triglyceride
C. glycerol-3-phosphate
D. phosphatidyl serine
44. The transport of lipid in the blood is carried out by transport lipoproteins that are capable of carrying cholesterol, fat and phospholipid in packages that have all the following properties EXCEPT
A. are water soluble.
B. have variable capacity for carrying fat and cholesterol, resulting in different densities.
C. contain different apolipoproteins to direct the delivery of their contents.
D. are all synthesized in the liver.
E. deliver cholesterol to cells by endocytosis.
45. Your patient has cholesterol levels within the normal range, but very high levels of lipoprotein (a). You warn him that he is at high risk of coronary disease because lipoprotein (a) appears to
A. not be taken up by endocytosis.
B. interfere with blood clot lysis.
C. increase cholesterol synthesis.
D. prevent HDL from collecting free cholesterol and returning it to the liver.
46. A patient is suffering from severe liver disease, resulting in inability to carry out effective urea production. Build up of ammonia in the blood ensues, and eventually leads to coma. The toxicity of ammonia in the brain is likely due to
A. production of carbamoyl-P in the brain.
B. increased activity of glutaminase.
C. conversion of a-ketoglutarate to glutamate and to glutamine, causing energy deprivation.
D. A and B are correct.
E. All of the above.
47. Bile salts are:
A. produced from cholesterol, by modifications that make it more hydrophobic.
B. excreted via the intestines, normally providing an effective system for eliminating excess cholesterol.
C. capable of hydrolyzing fatty acids off the glycerol backbone of phospholipids and triglycerides.
D. a component of the mixed micelles that are absorbed into the intestinal mucosa.
E. broken down to acetyl CoA as a source of energy.
48. Digestion of lipids in the gut involves all the following intermediates and enzymes EXCEPT
A. pancreatic lipase
B. monoacyl glycerol
C. bile salts
D. phospholipase
E. lipoprotein lipase
49. Hypercholesterolemia
A. is usually a result of inadequate mechanisms of control of cholesterol synthesis.
B. can result in plaque formation in the arteries due to oxidation of the phospholipid monolayer of circulating lipoproteins leading to their disintegration.
C. is only rarely caused by a defect in the receptor-mediated uptake of LDL from the blood.
D. when accompanied by high HDL levels means there is no risk of heart disease.
50. The statin drugs (e.g. Lipitor) are effective in lowering circulating cholesterol levels because they
A. inhibit HMG CoA synthase.
B. prevent absorption of dietary cholesterol in the gut.
C. increase conversion of cholesterol to bile salts.
D. inhibit cholesterol synthesis within the cell, which favors uptake from circulation.
51. Cholesterol uptake in the form of LDLs and processing in tissues, involves all the following steps or enzymes EXCEPT
A. apolipoprotein B100 binding to the LDL receptor.
B. hydrolysis of the lipid, protein and cholesterol esters in lysosomes.
C. re-esterification of free cholesterol by LCAT (lecithin:cholesterol acyl transferase).
D. formation of coated vesicles containing the LDL-receptor complex.
52. Synthesis of fatty acids may be stimulated when there is:
A. build up of acetyl CoA in mitochondria.
B. high levels of palmitate in the cytosol.
C. build up of citrate in mitochondria.
D. high levels of malate in mitochondria.
E. activation of acyl CoA synthetase in the cytosol.
53. The synthesis of a fatty acid by fatty acid synthase will
A. produce a 16 carbon polyunsaturated fatty acid.
B. require NADH as a source of reducing agents.
C. use acetyl CoA as a source of 2 C units.
D. be driven by release of CO2
E. make a C16 fatty acid in which the last 2 carbons added are carbon 15 and 16.
54. A patient is suffering from angina (heart pain); you prescribe a newly approved drug called Trimetazidine, which has been shown to inhibit fatty acid oxidation and stimulate glucose oxidation by the heart. You expect pain relief because complete oxidation of glucose produces
A. more ATP per mole than oxidation of fatty acid.
B. more ATP per carbon than oxidation of fatty acid.
C. more ATP per oxygen consumed than fatty acid.
D. all of the above.
55. For the effectors listed below, which one is correctly paired with an enzyme or pathway for which it is an ACTIVATOR
A. AMP : gluconeogenesis
B. citrate : glycolysis
C. Fructose-2,6 bisphosphate : glycolysis
D. palmitoyl CoA : fatty acid synthesis
E. malonyl CoA : fatty acid oxidation
56. Which of the following circulating fuels would be produced by adipose tissue when insulin is low:
A. lactate
B. glucose
C. amino acids
D. glycerol
E. ketone bodies
57. Which effect of glucagon in the liver or adipose tissue is correctly indicated ((+) = activation; (--) = inhibition) with respect to the pathway involved
A. glycogenolysis : (--)
B. lipolysis : (+)
C. glycolysis : (+)
D. lipogenesis : (+)
E. glycogenesis : (+)
58. Which of the following enzymes would not be activated when insulin levels are high:
A. acyltransferase
B. glycogen synthase
C. hormone sensitive lipase
D. pyruvate dehydrogenase
E. HMG CoA reductase
59. Which one of the key intermediates in metabolism listed below is paired with an enzyme that would neither directly produce nor consume it:
A. glucose-6-phosphate : glucokinase
B. pyruvate : alanine aminotransferase
C. acetyl CoA : pyruvate dehydrogenase
D. pyruvate : lactate dehydrogenase
E. pyruvate : acetyl CoA carboxylase
60. Glycation of protein (modification by covalent attachment of glucose)
A. occurs in the blood of diabetics but not in non-diabetics.
B. only affects hemoglobin.
C. can be used to measure blood glucose levels in diabetics.
D. is a highly reversible modification that does not affect protein function.
BMB 514
Final Exam
October 20, 2003


ANSWER KEY

Version of the Exam: 1A

1. C 11. D 21. B 31. A 41. E 51. C
2. D 12. D 22. A 32. D 42. C 52. C
3. D 13. A 23. E 33. E 43. C 53. D
4. B 14. B 24. E 34. A 44. D 54. C
5. E 15. B 25. B 35. D 45. B 55. C
6. A 16. E 26. D 36. D 46. C 56. D
7. E 17. D 27. D 37. C 47. D 57. B
8. B 18. A 28. C 38. B 48. E 58. C
9. A 19. B 29. C 39. D 49. B 59. E
10. C 20. C 30. D 40. A 50. D 60. C