Deck 16: The Citric Acid Cycle

Question 1

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.

Answer 1

All enzymes of the cycle are located in the cytoplasm,except succinate dehydrogenase,which is bound to the inner mitochondrial membrane.

Question 2

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

Answer 2

1/2

Question 3

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.

Answer 3

Biotin participates in the decarboxylation.

Question 4

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
E)Succinate

Question 5

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)( $\alpha$ -ketoglutarate to succinyl-CoA.)

Question 6

Which one of the following enzymatic activities would be decreased by thiamine deficiency?

A)Fumarase
B)Isocitrate dehydrogenase
C)Malate dehydrogenase
D)Succinate dehydrogenase
E)( $\alpha$ -Ketoglutarate dehydrogenase complex)

Question 7

The standard reduction potentials (E'°)for the following half reactions are given. Fumarate + 2H⁺ + 2e^- $\rightarrow$ succinate E'° = +0.031 V
FAD + 2H⁺ + 2e^- $\rightarrow$ 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.

Question 8

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.

Question 9

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

Question 10

The oxidative decarboxylation of $\alpha$ -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

Question 11

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.

Question 12

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⁺

Question 13

For the following reaction, $\Delta$ G'° = 29.7 kJ/mol. L-Malate + NAD⁺ $\rightarrow$ 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 $\Delta$ G'° is positive.
C)can only occur in a cell in which NADH is converted to NAD⁺ by electron transport.
D)may occur in cells at certain concentrations of substrate and product.
E)would always proceed at a very slow rate

Question 14

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.

Question 15

In mammals,each of the following occurs during the citric acid cycle except:

A)formation of $\alpha$ -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.

Question 16

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⁺

Question 17

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.

Question 18

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.

Question 19

Which of the following is not an intermediate of the citric acid cycle?

A)Acetyl-CoA
B)Citrate
C)Oxaloacetate
D)Succinyl-CoA
E)( $\alpha$ -Ketoglutarate)

Question 20

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.

Question 21

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

Question 22

The citric acid cycle begins with the condensation of acetyl-CoA with oxaloacetate.Describe three possible sources for the acetyl-CoA.

Question 23

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).

Question 24

Entry of acetyl-CoA into the citric acid cycle is decreased when:

A)[AMP] is high.
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.

Question 25

What is the function of FAD in the pyruvate dehydrogenase complex? How is it regenerated?

Question 26

Briefly describe the relationship of the pyruvate dehydrogenase complex reaction to glycolysis and the citric acid cycle.

Question 27

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

Question 28

Which of the following intermediates of the citric acid cycle is prochiral?

A)Citrate
B)Isocitrate
C)Malate
D)Oxaloacetate
E)Succinate

Question 29

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

Question 30

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

Question 31

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?

Question 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.

Question 33

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.

Question 34

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.

Question 35

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.

Question 36

Describe the enzymes,cofactors,intermediates,and products the pyruvate dehydrogenase complex.

Question 37

Match the cofactors below with their roles in the pyruvate dehydrogenase complex reaction.

Question 38

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⁺

Question 39

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 $\alpha$ -ketoglutarate dehydrogenase complex.

Question 40

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.

Question 41

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.

Question 42

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?

Question 43

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.

Question 44

Explain in quantitative terms the circumstances under which the following reaction can proceed.
L-Malate + NAD⁺ $\rightarrow$ oxaloacetate + NADH + H⁺ $\Delta$ G'° = +29.7 kJ/mol

Question 45

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.

Question 46

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.

Question 47

Explain why fluorocitrate,a potent inhibitor of the enzyme aconitase,is a deadly poison.

Question 48

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.

Question 49

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.

Question 50

Show the reactions by which $\alpha$ -ketoglutarate is converted to malate in the citric acid cycle.

Question 51

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).

Question 52

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.

Question 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).

Question 54

Match the cofactor with its function in the citric acid cycle.A given function may be used more than once or not at all.

Question 55

In which reaction of the citric acid cycle does substrate-level phosphorylation occur?

Question 56

At what point in the citric acid cycle do the methyl carbon from acetyl-CoA and the carbonyl carbon from oxaloacetate become chemically equivalent?

Question 57

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.

Question 58

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?