Biochem I - Ch. 16

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Which combination of cofactors is involved in the conversion of pyruvate to acetyl-CoA?

TPP, lipoic acid, and NAD+


Which statement about the oxidative decarboxylation of pyruvate in aerobic conditions in animal cells is correct?

One of the products of the reactions of the pyruvate dehydrogenase complex is a thioester of acetate.


Which of the following is not true of the citric acid cycle?

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


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?



What are the intermediates of the citric acid cycle?

B) Citrate
C) Oxaloacetate
D) Succinyl-coA
E) α-Ketoglutarate


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

net synthesis of oxaloacetate from acetyl-CoA


The two moles of CO2 produced in the first turn of the citric acid cycle have their origin in the:

two carboxyl groups derived from oxaloacetate


All of the oxidative steps of the citric acid cycle are linked to the reduction of NAD+ except the reaction catalyzed by

succinate dehydrogenase


Which of the following cofactors is required for the conversion of succinate to fumarate in the citric acid cycle



In the citric acid cycle, a flavin coenzyme is required for

oxidation of succinate.


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



Anaplerotic reactions

produce oxaloacetate and malate to maintain constant levels of citric acid cycle intermediates


Intermediates in the citric acid cycle may also be used as precursors in the biosynthesis of

A) amino acids
B) nucleotides
C) fatty acids
D) sterols


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).

4; 1; 1


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

the ratio of [ATP]/[ADP] 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

ATP and/or NADH


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

Substrate-level phosphorylation of GDP to GTP occurs in the succinyl-CoA synthetase reaction in which succinyl-CoA is converted to succinate during the citric acid cycle


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).

The oxidation of α-ketoglutarate to succinyl-CoA involves five cofactors: lipoate, thiamine pyrophosphate (TPP), FAD,
NAD+, and CoA-SH.


the citric acid cycle is frequently described as the major pathway of aerobic catabolism, which means that it is an oxygendependent
degradative process. However, none of the reactions of the cycle directly involves oxygen as a reactant. Why is the
pathway oxygen-dependent?

The citric acid cycle produces NADH, which normally is recycled by passage of electrons from NADH to O2 via the
respiratory chain. With no O2 to accept electrons from NADH, the accumulation of NADH effectively stops the citric acid


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

By inhibiting aconitase, fluorocitrate prevents the citric acid cycle from operating. This prevents the oxidation of acetyl-CoA and dramatically reduces the yield of ATP from carbohydrate and lipid catabolism. The resulting drop in ATP levels is lethal.


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

This happens with the formation of succinate.


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

The citric acid cycle is central to all aerobic energy-yielding metabolisms and also plays a critical role in biosynthetic
reactions by providing precursors. Mutations in the enzymes of the citric acid cycle are likely to be lethal during fetal


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

Thiamine is essential for the synthesis of the cofactor thiamine pyrophosphate (TPP). Without this cofactor the pyruvate
dehydrogenase complex cannot convert pyruvate into acetyl-CoA, so the pyruvate produced by glycolysis accumulates


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

FAD serves as the electron acceptor in the re-oxidation of the cofactor dihydrolipoate. It is converted to FADH2 by this reaction and is regenerated by the passage of electrons to NAD+.


Cofactor: Coenzyme A (CoA-SH)

Accepts the acetyl group from reduced lipoic acid.


Cofactor:Lipoic acid in oxidized form

Oxidizes the reduced form of lipoic acid.



Initial electron acceptor in oxidation of pyruvate


Thiamine pyrophosphate (TPP)

Attacks and attaches to the central carbon in pyruvate



Oxidizes FADH2.


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

The pyruvate dehydrogenase complex converts pyruvate, the product of glycolysis, into acetyl-CoA, the starting material
for the citric acid cycle


The citric acid cycle begins with condensation of acetyl-CoA with oxaloacetate. Describe 3 possible sources for the acetyl-CoA

Acetyl-CoA is produced by (1) the pyruvate dehydrogenase complex, (2) β oxidation of fatty acids, or (3) degradation of
certain amino acids