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Chapter 16 The Citric Acid Cycle
Multiple Choice Questions
1. Which of the following is not true of the reaction catalyzed by the pyruvate dehydrogenase complex?
A) Biotin participates in the decarboxylation.
B) Both NAD+ and a flavin nucleotide act as electron carriers.
C) The reaction occurs in the mitochondrial matrix.
D) The substrate is held by the lipoyl-lysine “swinging arm.”
E) Two different cofactors containing —SH groups participate.
2. Which of the below is not required for the oxidative decarboxylation of pyruvate to form acetyl-CoA?
A) ATP
B) CoA-SH
C) FAD
D) Lipoic acid
E) NAD+
3. Which combination of cofactors is involved in the conversion of pyruvate to acetyl-CoA?
A) Biotin, FAD, and TPP
B) Biotin, NAD+, and FAD
C) NAD+, biotin, and TPP
D) Pyridoxal phosphate, FAD, and lipoic acid
E) TPP, lipoic acid, and NAD+
4. Which of the following statements about the oxidative decarboxylation of pyruvate in aerobic
conditions in animal cells is correct?
A) One of the products of the reactions of the pyruvate dehydrogenase complex is a thioester of
acetate.
B) The methyl (—CH3) group is eliminated as CO2.
C) The process occurs in the cytosolic compartment of the cell.
D) The pyruvate dehydrogenase complex uses all of the following as cofactors: NAD+, lipoic acid,
pyridoxal phosphate (PLP), and FAD.
E) The reaction is so important to energy production that pyruvate dehydrogenase operates at full
speed under all conditions.
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5. Glucose labeled with 14C in C-3 and C-4 is completely converted to acetyl-CoA via glycolysis and the
pyruvate dehydrogenase complex. What percentage of the acetyl-CoA molecules formed will be
labeled with 14C, and in which position of the acetyl moiety will the 14C label be found?
A) 100% of the acetyl-CoA will be labeled at C-1 (carboxyl).
B) 100% of the acetyl-CoA will be labeled at C-2.
C) 50% of the acetyl-CoA will be labeled, all at C-2 (methyl).
D) No label will be found in the acetyl-CoA molecules.
E) Not enough information is given to answer this question.
6. Which of the following is not true of the citric acid cycle?
A) All enzymes of the cycle are located in the cytoplasm, except succinate dehydrogenase, which is
bound to the inner mitochondrial membrane.
B) In the presence of malonate, one would expect succinate to accumulate.
C) Oxaloacetate is used as a substrate but is not consumed in the cycle.
D) Succinate dehydrogenase channels electrons directly into the electron transfer chain.
E) The condensing enzyme is subject to allosteric regulation by ATP and NADH.
7. Acetyl-CoA labeled with 14C in both of its acetate carbon atoms is incubated with unlabeled
oxaloacetate and a crude tissue preparation capable of carrying out the reactions of the citric acid
cycle. After one turn of the cycle, oxaloacetate would have 14C in:
A) all four carbon atoms.
B) no pattern that is predictable from the information provided.
C) none of its carbon atoms.
D) the keto carbon and one of the carboxyl carbons.
E) the two carboxyl carbons.
8. Malonate is a competitive inhibitor of succinate dehydrogenase. If malonate is added to a
mitochondrial preparation that is oxidizing pyruvate as a substrate, which of the following
compounds would you expect to decrease in concentration?
A) Citrate
B) Fumarate
C) Isocitrate
D) Pyruvate
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187
E) Succinate
9. Which of the following is not an intermediate of the citric acid cycle?
A) Acetyl-CoA
B) Citrate
C) Oxaloacetate
D) Succinyl-CoA
E) -Ketoglutarate
10. In mammals, each of the following occurs during the citric acid cycle except:
A) formation of -ketoglutarate.
B) generation of NADH and FADH2.
C) metabolism of acetate to carbon dioxide and water.
D) net synthesis of oxaloacetate from acetyl-CoA.
E) oxidation of acetyl-CoA.
11. Oxaloacetate uniformly labeled with 14C (i.e., with equal amounts of 14C in each of its carbon atoms)
is condensed with unlabeled acetyl-CoA. After a single pass through the citric acid cycle back to
oxaloacetate, what fraction of the original radioactivity will be found in the oxaloacetate?
A) All
B) 1/2
C) 1/3
D) 1/4
E) 3/4
12. Conversion of 1 mol of acetyl-CoA to 2 mol of CO2 and CoA via the citric acid cycle results in the
net production of:
A) 1 mol of citrate.
B) 1 mol of FADH2.
C) 1 mol of NADH.
D) 1 mol of oxaloacetate.
E) 7 mol of ATP.
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13. Which one of the following is not associated with the oxidation of substrates by the citric acid cycle?
A) All of the below are involved.
B) CO2 production
C) Flavin reduction
D) Lipoic acid present in some of the enzyme systems
E) Pyridine nucleotide oxidation
14. The two moles of CO2 produced in the first turn of the citric acid cycle have their origin in the:
A) carboxyl and methylene carbons of oxaloacetate
B) carboxyl group of acetate and a carboxyl group of oxaloacetate.
C) carboxyl group of acetate and the keto group of oxaloacetate.
D) two carbon atoms of acetate.
E) two carboxyl groups derived from oxaloacetate.
Reactions of the citric acid cycle
15. The oxidative decarboxylation of -ketoglutarate proceeds by means of multistep reactions in which
all but one of the following cofactors are required. Which one is not required?
A) ATP
B) Coenzyme A
C) Lipoic acid
D) NAD+
E) Thiamine pyrophosphate
16. The reaction of the citric acid cycle that is most similar to the pyruvate dehydrogenase complex-
catalyzed conversion of pyruvate to acetyl-CoA is the conversion of:
A) citrate to isocitrate.
B) fumarate to malate.
C) malate to oxaloacetate.
D) succinyl-CoA to succinate.
E) -ketoglutarate to succinyl-CoA.
17. Which one of the following enzymatic activities would be decreased by thiamine deficiency?
Chapter 16 The Citric Acid Cycle
189
A) Fumarase
B) Isocitrate dehydrogenase
C) Malate dehydrogenase
D) Succinate dehydrogenase
E) -Ketoglutarate dehydrogenase complex
18. The reaction of the citric acid cycle that produces an ATP equivalent (in the form of GTP) by
substrate level phosphorylation is the conversion of:
A) citrate to isocitrate.
B) fumarate to malate.
C) malate to oxaloacetate.
D) succinate to fumarate.
E) succinyl-CoA to succinate.
Reactions of the citric acid cycle
19. The standard reduction potentials (E'°) for the following half reactions are given.
Fumarate + 2H+ + 2e– → succinate E'° = +0.031 V
FAD + 2H+ + 2e– → FADH2 E'° = –0.219 V
If succinate, fumarate, FAD, and FADH2, all at l M concentrations, were mixed together in the
presence of succinate dehydrogenase, which of the following would happen initially?
A) Fumarate and succinate would become oxidized; FAD and FADH2 would become reduced.
B) Fumarate would become reduced; FADH2 would become oxidized.
C) No reaction would occur because all reactants and products are already at their standard
concentrations.
D) Succinate would become oxidized; FAD would become reduced.
E) Succinate would become oxidized; FADH2 would be unchanged because it is a cofactor, not a
substrate.
20. For the following reaction, G'° = 29.7 kJ/mol.
L-Malate + NAD+ → oxaloacetate + NADH + H+
The reaction as written:
A) can never occur in a cell.
B) can only occur in a cell if it is coupled to another reaction for which G'° is positive.
C) can only occur in a cell in which NADH is converted to NAD+ by electron transport.
Chapter 16 The Citric Acid Cycle
190
D) may occur in cells at certain concentrations of substrate and product.
E) would always proceed at a very slow rate
21. All of the oxidative steps of the citric acid cycle are linked to the reduction of NAD+ except the
reaction catalyzed by:
A) isocitrate dehydrogenase.
B) malate dehydrogenase.
C) pyruvate dehydrogenase
D) succinate dehydrogenase.
E) the -ketoglutarate dehydrogenase complex.
22. Which of the following cofactors is required for the conversion of succinate to fumarate in the citric
acid cycle?
A) ATP
B) Biotin
C) FAD
D) NAD+
E) NADP+
23. In the citric acid cycle, a flavin coenzyme is required for:
A) condensation of acetyl-CoA and oxaloacetate.
B) oxidation of fumarate.
C) oxidation of isocitrate.
D) oxidation of malate.
E) oxidation of succinate.
24. Which of the following intermediates of the citric acid cycle is prochiral?
A) Citrate
B) Isocitrate
C) Malate
D) Oxaloacetate
E) Succinate
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191
25. Anaplerotic reactions .
A) produce oxaloacetate and malate to maintain constant levels of citric acid cycle intermediates
B) produce biotin needed by pyruvate carboxylase
C) recycle pantothenate used to make CoA
D) produce pyruvate and citrate to maintain constant levels of citric acid cycle intermediates
E) All of the above
26. Intermediates in the citric acid cycle are used as precursors in the biosynthesis of:
A) amino acids.
B) nucleotides.
C) fatty acids.
D) sterols.
E) All of the above
27. The conversion of 1 mol of pyruvate to 3 mol of CO2 via pyruvate dehydrogenase and the citric acid
cycle also yields _____ mol of NADH, _____ mol of FADH2, and _____ mol of ATP (or GTP).
A) 2; 2; 2
B) 3; 1; 1
C) 3; 2; 0
D) 4; 1; 1
E) 4; 2; 1
28. During the reaction of pyruvate carboxylase, CO2 is covalently attached to all the following except:
A) phosphate.
B) biotin.
C) pyruvate.
D) lysine.
E) All of the above
29. Entry of acetyl-CoA into the citric acid cycle is decreased when:
A) [AMP] is high.
Chapter 16 The Citric Acid Cycle
192
B) NADH is rapidly oxidized through the respiratory chain.
C) the ratio of [ATP]/[ADP is low
D) the ratio of [ATP]/[ADP] is high.
E) the ratio of [NAD+]/[NADH] is high.
30. Citrate synthase and the NAD+-specific isocitrate dehydrogenase are two key regulatory enzymes of
the citric acid cycle. These enzymes are inhibited by:
A) acetyl-CoA and fructose 6-phosphate.
B) AMP and/or NAD+.
C) AMP and/or NADH.
D) ATP and/or NAD+.
E) ATP and/or NADH.
31. During seed germination, the glyoxylate pathway is important to plants because it enables them to:
A) carry out the net synthesis of glucose from acetyl-CoA.
B) form acetyl-CoA from malate.
C) get rid of isocitrate formed from the aconitase reaction.
D) obtain glyoxylate for cholesterol biosynthesis.
E) obtain glyoxylate for pyrimidine synthesis.
32. A function of the glyoxylate cycle, in conjunction with the citric acid cycle, is to accomplish the:
A) complete oxidation of acetyl-CoA to CO2 plus reduced coenzymes.
B) net conversion of lipid to carbohydrate.
C) net synthesis of four-carbon dicarboxylic acids from acetyl-CoA.
D) net synthesis of long-chain fatty acids from citric acid cycle intermediates.
E) Both B and C are correct.
33. The glyoxylate cycle is:
A) a means of using acetate for both energy and biosynthetic precursors.
B) an alternative path of glucose metabolism in cells that do not have enough O2.
C) defective in people with phenylketonuria.
D) is not active in a mammalian liver.
E) the most direct way of providing the precursors for synthesis of nucleic acids (e.g., ribose).
Chapter 16 The Citric Acid Cycle
193
Short Answer Questions
34. The citric acid cycle begins with the condensation of acetyl-CoA with oxaloacetate. Describe three
possible sources for the acetyl-CoA.
35. Briefly describe the relationship of the pyruvate dehydrogenase complex reaction to glycolysis and
the citric acid cycle.
36. Describe the enzymes, cofactors, intermediates, and products the pyruvate dehydrogenase complex.
37. Suppose you found an overly high level of pyruvate in a patient’s blood and urine. One possible
cause is a genetic defect in the enzyme pyruvate dehydrogenase, but another plausible cause is a
specific vitamin deficiency. Explain what vitamin might be deficient in the diet, and why that would
account for high levels of pyruvate to be excreted in the urine. How would you determine which
explanation is correct?
Chapter 16 The Citric Acid Cycle
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38. Match the cofactors below with their roles in the pyruvate dehydrogenase complex reaction.
Cofactors:
A. Coenzyme A (CoA-SH)
B. NAD+
C. Thiamine pyrophosphate (TPP)
D. FAD
E. Lipoic acid in oxidized form
Roles:
_______ Attacks and attaches to the central carbon in pyruvate
_______ Oxidizes FADH2
_______ Accepts the acetyl group from reduced lipoic acid
_______ Oxidizes the reduced form of lipoic acid
_______ Initial electron acceptor in oxidation of pyruvate.
39. Two of the steps in the oxidative decarboxylation of pyruvate to acetyl-CoA do not involve the three
carbons of pyruvate, yet are essential to the operation of the pyruvate dehydrogenase complex.
Explain.
40. What is the function of FAD in the pyruvate dehydrogenase complex? How is it regenerated?
41. The human disease beriberi is caused by a deficiency of thiamine in the diet. People with severe
beriberi have higher than normal levels of pyruvate in their blood and urine. Explain this observation
in terms of specific enzymatic reaction(s).
Chapter 16 The Citric Acid Cycle
195
42. There are few, if any, humans with defects in the enzymes of the citric acid cycle. Explain this
observation in terms of the role of the citric acid cycle.
43. Preparation of an extract of muscle results in a dramatic decrease in the concentration of citric acid
cycle intermediates compared to their concentrations in the tissue. However, in 1935, Szent-Gyorgi
showed that the production of CO2 by the extract increased when succinate was added. In fact, for
every mole of succinate added, many extra moles of CO2 were produced. Explain this effect in terms
of the known catabolic pathways.
44. Draw the citric acid cycle from isocitrate to fumarate only, showing and naming each intermediate.
Show where high-energy phosphate compounds or reduced electron carriers are produced or
consumed, and name the enzyme that catalyzes each step.
45. Show the three reactions in the citric acid cycle in which NADH is produced, including the structures.
None of these reactions involves molecular oxygen (O2), but all three reactions are strongly inhibited
by anaerobic conditions; explain why.
46. At what point in the citric acid cycle do the methyl carbon from acetyl-CoA and the carbonyl carbon
from oxaloacetate become chemically equivalent?
Chapter 16 The Citric Acid Cycle
196
47. Show the reactions by which -ketoglutarate is converted to malate in the citric acid cycle.
48. Show the steps of the citric acid cycle in which a six-carbon compound is converted into the first
four-carbon intermediate in the path. For each step, show structures of substrate and product, name
the enzyme responsible, and show where cofactors participate.
49. Show the structures of the reactants and products for two of the four redox reactions in the citric acid
cycle. Indicate where any cofactors participate, and label the reactants, products, and cofactors as
oxidants or reductants in the reaction.
50. Show the steps of the citric acid cycle from succinyl-CoA to oxaloacetate only. For each step, show
structures of substrate and product, name the enzyme responsible, and show where cofactors
participate.
51. Explain why fluorocitrate, a potent inhibitor of the enzyme aconitase, is a deadly poison.
Chapter 16 The Citric Acid Cycle
197
52. The citric acid cycle is frequently described as the major pathway of aerobic catabolism, which means
that it is an oxygen-dependent degradative process. However, none of the reactions of the cycle
directly involves oxygen as a reactant. Why is the pathway oxygen-dependent?
53. In the citric acid cycle, a five-carbon compound is decarboxylated to yield an activated four-carbon
compound. Show the substrate and product in this step, and indicate where any cofactor(s)
participate(s).
54. CO2 is produced in two reactions in the citric acid cycle. For each of these reactions, name and show
the structures of reactant and product, name the enzyme, and show how any cofactors participate.
55. In which reaction of the citric acid cycle does substrate-level phosphorylation occur?
56. Explain in quantitative terms the circumstances under which the following reaction can proceed.
L-Malate + NAD+ → oxaloacetate + NADH + H+ G'° = +29.7 kJ/mol
Chapter 16 The Citric Acid Cycle
198
57. You are in charge of genetically engineering a new bacterium that will derive all of its ATP from
sunlight by photosynthesis. Will you put the enzymes of the citric acid cycle in this organism?
Briefly explain why or why not.
58. Match the cofactor with its function in the citric acid cycle. A given function may be used more than
once or not at all.
Cofactor Function
(a) NAD+/NADH (1) carries O2
(b) FAD/FADH2 (2) carries small carbon-containing molecules
(c) CoA (3) carries e-
(d) thiamine (4) carries small nitrogen-containing molecules
(e) biotin
59. Germinating plant seeds can convert stored fatty acids into oxaloacetate and a variety of
carbohydrates. Animals cannot synthesize significant quantities of oxaloacetate or glucose from fatty
acids. What accounts for this difference?
