Chapter 16 - The Citric Acid Cycle Flashcards

Which statement 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.

Which compound 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+

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+

Which statement 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.

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.

Which statement 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.

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.

Malonate is a competitive inhibitor of succinate dehydrogenase. If malonate is added to a mitochondrial preparation that is
oxidizing pyruvate as a substrate, which compound would you expect to decrease in concentration?
A) citrate
B) fumarate
C) isocitrate
D) pyruvate
E) succinate

Which compound is NOT an intermediate of the citric acid cycle?
A) acetyl-CoA
B) citrate
C) oxaloacetate
D) succinyl-CoA
E) α-ketoglutarate

In mammals, what process does NOT occur during the citric acid cycle?
A) formation of α-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

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

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.

Which factor is NOT associated with the oxidation of substrates by the citric acid cycle?
A) CO2 production
B) flavin reduction
C) the presence of lipoic acid in some of the enzyme systems
D) pyridine nucleotide oxidation
E) All of these factors are associated with the oxidation of substrates by the citric acid cycle.

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.

The oxidative decarboxylation of α-ketoglutarate proceeds by means of multistep reactions. Which cofactor is NOT
required?
A) ATP
B) coenzyme A
C) lipoic acid
D) NAD+
E) thiamine pyrophosphate

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) α-ketoglutarate to succinyl-CoA.

Which enzymatic activity would be decreased by thiamine deficiency?
A) fumarase
B) isocitrate dehydrogenase
C) malate dehydrogenase
D) succinate dehydrogenase
E) α-ketoglutarate dehydrogenase complex

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.

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.

For the following reaction, ΔG'° = 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 ΔG'° 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

The oxidative step of the citric acid cycle that is NOT linked to the reduction of NAD+ is the reaction catalyzed by:
A) isocitrate dehydrogenase.
B) malate dehydrogenase.
C) pyruvate dehydrogenase
D) succinate dehydrogenase.
E) the α-ketoglutarate dehydrogenase complex.

Which cofactor is required for the conversion of succinate to fumarate in the citric acid cycle?
A) ATP
B) biotin
C) FAD
D) NAD+
E) NADP+

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.

Which intermediate of the citric acid cycle is prochiral?
A) citrate
B) isocitrate
C) malate
D) oxaloacetate
E) succinate

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 answers are correct.

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 answers are correct.

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

During the reaction of pyruvate carboxylase, CO2 is NOT covalently attached to:
A) phosphate.
B) biotin.
C) pyruvate.
D) lysine.
E) All of the answers are correct.

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.

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.

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.

A function of the glyoxylate cycle, in conjunction with the citric acid cycle, is to accomplish:
A) the complete oxidation of acetyl-CoA to CO2 plus reduced coenzymes.
B) the net conversion of lipid to carbohydrate.
C) the net synthesis of four-carbon dicarboxylic acids from acetyl-CoA.
D) the net synthesis of long-chain fatty acids from citric acid cycle intermediates.
E) both the net conversion of lipid to carbohydrate and the net synthesis of four-carbon dicarboxylic acids from acetyl-
CoA.

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).

Which process is NOT a metabolic fate for pyruvate in liver tissue?
A) reduction to lactate
B) oxidative decarboxylation to acetyl-CoA
C) transamination to alanine
D) phosphorylation to phosphoenolpyruvate
E) carboxylation to oxaloacetate

The pyruvate dehydrogenase complex and the α-ketoglutarate dehydrogenase complex are homologous enzyme assemblies
that require several different coenzymes to carry out their reactions. Which compound does NOT participate directly in the
function of these complexes?
A) flavin mononucleotide
B) coenzyme A
C) lipoic acid
D) thiamine pyrophosphate
E) nicotinamide adenine dinucleotide

Which compound is NOT required for the oxidative decarboxylation of α-ketoglutarate?
A) FAD
B) lipoic acid
C) NAD+
D) ATP
E) CoA-SH

Covalent modification is one way the activity of specific enzymes can be regulated. Which enzyme is NOT regulated in this
way?
A) phosphofructokinase-2
B) α-ketoglutarate dehydrogenase
C) pyruvate dehydrogenase
D) phosphorylase kinase
E) All of these enzymes are regulated by covalent modification.

Which statement is FALSE regarding the reaction catalyzed by the α-ketoglutarate dehydrogenase complex?
A) A long lipollysyl arm transfers intermediates from one active site to another within the complex.
B) This reaction would be expected to be abnormally low in a person suffering from beriberi, a dietary deficiency of
thiamine.
C) Two different coenzymes containing sulfhydryl groups participate in the overall reaction.
D) Both this complex and the pyruvate dehydrogenase complex contain a common subunit.
E) The proximity of the catalytic enzymes allows for side-reactions to take place in the cluster.

Which enzyme does NOT have water as a substrate in the reaction it catalyzes?
A) succinyl-CoA sythetase
B) aconitase
C) fumarase
D) citrate synthase
E) succinyl-CoA sythetase and aconitase

Which statement about NAD+ and NADH is TRUE?
A) NADH inhibits the pyruvate dehydrogenase complex.
B) NAD+ is oxidized to NADH by the α-ketoglutarate dehydrogenase complex.
C) NAD+ is a coenzyme for two of the enzymes in the pyruvate dehydrogenase complex.
D) NAD+ is oxidized to NADH by isocitrate dehydrogenase.
E) NAD+ is oxidized to NADH by both isocitrate dehydrogenase and the α-ketoglutarate dehydrogenase complex.

Which enzyme catalyzes a reversible reaction under normal cellular conditions?
A) α-ketoglutarate dehydrogenase
B) isocitrate dehydrogenase
C) succinate dehydrogenase
D) pyruvate dehydrogenase
E) None of the answers is correct.

Which statement is FALSE regarding the citric acid cycle?
A) Succinate dehydrogenase is a flavoprotein associated with the electron-transport chain.
B) The rate of the citric acid cycle increases when the NAD+/NADH ratio is high.
C) In eukaryotes, the citric acid cycle occurs in the mitochondrial matrix.
D) Acetyl-CoA inhibits the α-ketoglutarate dehydrogenase complex.
E) All of the statements are false.

When is the consumption of acetyl-CoA by the citric acid cycle is decreased?
A) when the concentration of NAD+ is high
B) when the concentration of oxaloacetate is high
C) when NADH is rapidly reoxidized via the electron transport chain
D) when the mitochondrial ATP synthase is inactive
E) when the concentrations of NAD+ and oxaloacetate are both high

How much carbon dioxide is produced from the complete aerobic catabolism of one molecule of 2-phosphoglycerate via
catabolic pathways?
A) 2 CO2
B) 3 CO2
C) 4 CO2
D) 5 CO2
E) 6 CO2

Shown below is a list of pairs of compounds. In which pair is the second compound produced by a reduction of the first
compound?
A) fumarate and succinate
B) oxaloacetate and citrate
C) fumarate and malate
D) malate and oxaloacetate
E) isocitrate and α-ketoglutarate

Which statement about the oxidative decarboxylation of pyruvate in animal cells is CORRECT?
A) One of the products of this reaction is a molecule containing a thioether bond.
B) It only occurs under aerobic conditions.
C) The process occurs in the glyoxysome compartment of the cell.
D) It is often considered the first step in the glyoxylate cycle, as it generates acetyl-CoA, which is required by this pathway.
E) It is the most important anaplerotic reaction in hepatocytes.

Which cofactor is required for the conversion of fumarate to succinate?
A) FAD
B) GDP
C) CoA
D) FADH2
E) both GDP and CoA

Which citric acid cycle intermediate is chiral?
A) citrate
B) α-ketoglutarate
C) fumarate
D) succinate
E) malate

Thyroxine is a competitive inhibitor of malate dehydrogenase. If thyroxine is added to a mitochondrial preparation that is
oxidizing pyruvate as a substrate, which compound would you expect to decrease in concentration FIRST?
A) citrate
B) fumarate
C) oxaloacetate
D) pyruvate
E) malate

Which statement is FALSE with respect to the pyruvate dehydrogenase complex?
A) It is located in the mitochondrial matrix.
B) Its activity is increased in the presence of Ca2+ ions in skeletal muscle.
C) Its activity is increased in the presence of coenzyme A and ADP.
D) The proximity of the catalytic enzymes in the cluster slows down the overall rate.
E) All of the statements are false.

Arsenic inhibits the pyruvate dehydrogenase complex by inactivating the dihydrolipoamide component of dihydrolipoyl
transacetylase. Which enzyme is also MOST likely to be inhibited by arsenic?
A) GAP dehydrogenase
B) isocitrate dehydrogenase
C) succinyl-CoA synthetase
D) malate dehydrogenase
E) α-ketoglutarate dehydrogenase

Which enzymes catalyze oxidation reactions in the citric acid cycle?
1) succinate dehydrogenase
2) pyruvate dehydrogenase
3) citrate dehydrogenase
4) α-ketoglutarate dehydrogenase
A) 1 and 4
B) 1, 2, and 4
C) 1, 3, and 4
D) 2 and 3
E) All of the listed enzymes catalyze oxidation reactions in the citric acid cycle.

Which reaction in the citric acid cycle will NOT proceed in the absence of inorganic phosphate ions?
A) the reaction catalyzed by α-ketoglutarate dehydrogenase
B) the reaction catalyzed by succinate dehydrogenase
C) the reaction catalyzed by succinyl-CoA synthetase
D) the reaction catalyzed by aconitase
E) the reaction catalyzed by fumarase

Why is the citric acid cycle considered to be part of aerobic metabolism, even though oxygen is not a substrate in any
reaction?
A) because it takes place in the mitochondrion
B) because it contains oxidation reactions
C) because it produces reduced electron carriers, which are reoxidized by transferring their electrons ultimately to oxygen
D) because NADH and FADH2 produce a lot of ATP when reoxidized
E) because it produces carbon dioxide

Which reaction of the citric acid cycle produces a net of one water molecule?
A) citrate to isocitrate
B) fumarate to malate
C) succinyl-CoA to succinate
D) succinate to succinyl-CoA
E) None of the answers is correct.

Which reaction of the citric acid cycle requires a water molecule?
A) formation of citrate
B) succinyl-CoA to succinate
C) fumarate to malate
D) All of the answers are correct.
E) None of the answers is correct.

Which cofactors associated with the pyruvate dehydrogenase complex are classified as prosthetic groups?
1) TPP
2) lipoate
3) CoA-SH
4) NAD+
5) FAD
A) 1 and 5
B) 1, 2, and 4
C) 1, 2, and 5
D) 3 and 4
E) 4 and 5

Which high-energy bond is associated with the succinyl-CoA synthetase reaction?
A) acyl phosphate
B) thioester
C) phosphohistidine
D) mixed anhydride
E) All of the answers are correct.

Which compound is NOT required for the oxidative decarboxylation of the carbon skeleton of isoleucine?
A) FAD
B) thiamine pyrophosphate
C) NAD+
D) CoA-SH
E) All are these compounds are required.

Which molecule is an α-keto acid?
A) oxaloacetate
B) citrate
C) α-ketoglutarate
D) oxaloacetate and α-ketoglutarate
E) citrate and α-ketoglutarate

What process occurs in the citric acid cycle?
A) formation of a mixed anhydride (acyl phosphate)
B) net synthesis of oxaloacetate from two acetyl-CoA molecules
C) hydrolysis of two thioester bonds
D) All of the answers are correct.
E) None of the answers is correct.

Which enzyme in the citric acid cycle has a standard free energy that is large and positive?
A) malate dehydrogenase
B) citrate synthase
C) succinyl-CoA synthetase
D) fumarase
E) No enzyme in the CAC has a positive ΔG′°.

Which step is NOT catalyzed by the pyruvate dehydrogenase complex?
A) E1 catalyzes the decarboxylation of pyruvate.
B) E1 catalyzes the oxidation of a hydroxyethyl group to an acetyl group.
C) E2 catalyzes the transfer of an acetyl group to CoA-SH
D) E3 catalyzes the reduction of oxidized lipoate.
E) E3 catalyzes the transfer of electrons from FADH2 to NAD+.

How many ATP equivalents are made from the aerobic conversion of pyruvate to oxaloacetate?
A) 9 ATP
B) 10 ATP
C) 11 ATP
D) 11.5 ATP
E) 12.5 ATP

Which statement is FALSE regarding regulation of the pyruvate dehydrogenase complex?
A) In E. coli, a high ratio of [NAD+]/[NADH] activates the complex.
B) In E. coli, high levels of ATP enhance the activity of pyruvate dehydrogenase kinase.
C) In plants, NH4+ inhibits the complex by enhancing the activity of pyruvate dehydrogenase kinase.
D) In mammals, both fatty acids and acetyl-CoA inhibit the complex.
E) In skeletal muscle, both NAD+ and Ca2+ activate the complex.

Which vitamin is NOT a precursor for a cofactor in the pyruvate dehydrogenase complex?
A) thiamine for TPP
B) riboflavin for FAD
C) niacin for lipoate
D) nictotinamide for NAD+
E) pantothenate for CoA

Which type of reaction is found in the citric acid cycle?
A) isomerization
B) hydration
C) condensation
D) redox
E) All of the answers are correct.

Which enzyme class is NOT found in the citric acid cycle?
A) oxidoreductase
B) hydrolase
C) ligase
D) lyase
E) isomerase

Which statement is FALSE regarding the glyoxylate cycle?
A) The glyoxylate cycle utilizes three of the eight enzymes associated with the citric acid cycle.
B) In the glyoxylate cycle, the two decarboxylation reactions of the citric acid cycle are bypassed, allowing for the net
synthesis of two succinate molecules.
C) The glyoxylate cycle is an anabolic pathway occurring in plants and certain microorganisms.
D) Because mammals lack the glyoxylate cycle, they cannot convert acetate from the oxidation of fatty acids to glucose.
E) The glyoxylate cycle allows plants to use acetate as a source of carbon and as a source of energy.

Which three of the choices listed are possible sources for acetyl-CoA that enters the citric acid cycle?
1. oxidative decarboxylation of pyruvate
2. β oxidation of fatty acids
3. catabolism of certain amino acids
4. citrate
5. carboxylation of pyruvate
A) 1, 2, and 3
B) 1, 2, and 4
C) 1, 2, and 5
D) 1, 4, and 4
E) 2, 4, and 5

The glyoxylate cycle in germinating seeds is a pathway that has some similarity to the citric acid cycle. It uses the carbonbased
products from the catabolism of fatty acids as the precursors for gluconeogenesis. How can the glyoxylate cycle
accomplish this?
A) It produces an excess of citrate, which is exported out of the mitochondria.
B) Its reactions take place partly in the matrix of the mitochondria and partly in the cytosol.
C) It uses only the catabolic products of even-numbered, saturated fatty acids.
D) Its reactions bypass the decarboxylation steps of the citric acid cycle.
E) It prevents the formation of malate, allowing carbons from acetate to form oxaloacetate.

The citric acid cycle has an important anabolic function by:
A) allowing for the conversion of certain carbon atoms from even-chain fatty acids into glucose.
B) producing lactate for gluconeogenesis.
C) providing metabolites for the synthesis of cholesterol, amino acids and glucose.
D) completing the oxidation of acetyl-CoA and storing electrons in the form of NADH.
E) All the answers are correct.

Why is flux through the citric acid low in the resting state?
A) Flux through the cycle is low due to a drop in serum adrenaline levels.
B) Flux through the cycle is low due to allosteric inhibition of pyruvate carboxylase.
C) Flux through the cycle is low due to complete oxidation of NADH because oxygen is readily available.
D) Flux through the cycle is low due to low local concentrations of NAD+ because of a diminished rate of oxidative
phosphorylation.
E) Flux through the cycle is low due to product inhibition of the pyruvate dehydrogenase complex by ATP.