Deck 16: Pyruvate Dehydrogenase Complex and the TCA Cycle

Question 1

In exercising skeletal muscles, pyruvate oxidation in the TCA cycle is stimulated by which of the following?

A) allosteric activation of isocitrate dehydrogenase by NADH
B) allosteric activation of malate dehydrogenase by NAD⁺
C) increased product inhibition of citrate synthase by oxaloacetate
D) phosphorylation of α-ketoglutarate dehydrogenase to an inactive form
E) stimulation of pyruvate dehydrogenase activity by Ca²⁺

Answer 1

E
EXPLANATION: Muscle contraction results in release of stored calcium ion from sarcoplasmic reticulum. The released calcium allosterically inhibits the activity of the PDH kinases. Reduced activity of PDH kinases results in reduced phosphorylation of the PDHc thus, allowing for greater oxidation of pyruvate.

Question 2

The pyruvate dehydrogenase complex (PDHc) is a multi-subunit enzyme whose activity is regulated by both allosteric effectors and covalent modification. Which of the following exerts a positive influence on the activity of PDHc toward pyruvate?

A) acetyl-CoA
B) ATP
C) dephosphorylation
D) NADH
E) phosphorylation

Answer 2

dephosphorylation

Question 3

A 24-year-old woman presents with diarrhea, dysphagia, jaundice, and white transverse lines on the fingernails (Mees lines). The patient is diagnosed with arsenic poisoning. Arsenic is known to inhibit which of the following enzymes of TCA cycle?

A) aconitase
B) citrate synthase
C) α-ketoglutarate dehydrogenase
D) malate dehydrogenase
E) succinate dehydrogenase

Answer 3

α-ketoglutarate dehydrogenase

Question 4

Which of the following vitamins is needed for the synthesis of a cofactor required for the conversion of succinate to fumarate?

A) lipoic acid
B) niacin
C) pantothenic acid
D) riboflavin
E) thiamine

Question 5

Pyruvate dehydrogenase complex (PDHc) deficiency is an autosomal recessive disorder and leads to anion gap metabolic acidosis. Which of the following accumulates to cause metabolic acidosis?

A) acetoacetate
B) fumarate
C) b-hydroxy butyrate
D) hydrochloric acid
E) lactate

Question 6

A 3-year-old child presents with a history of recurrent rash upon sun exposure and passage of purple-colored urine. The child is diagnosed with congenital erythropoietic porphyria (CEP), a disorder associated with the pathway of heme biosynthesis. Which of the following intermediates of TCA cycle is used as a precursor for heme biosynthesis?

A) acetyl-CoA
B) malate
C) pyruvate
D) succinate
E) succinyl-CoA

Question 7

A 2-year-old child was brought to pediatric emergency with convulsions. The child was diagnosed with ammonia intoxication due to some urea cycle disorder. Reduced formation of GABA, due to depletion ofglutamate, which serves as the precursor for its synthesis, is considered to be the most important cause of the convulsions. Which of the following intermediates of TCA cycle is involved in the formation of glutamate?

A) isocitrate
B) α-ketoglutarate
C) malate
D) pyruvate
E) succinate

Question 8

In the TCA cycle, GTP is produced via a process referred to as substrate-level phosphorylation. Which of the following enzymes is involved in this process of formation of GTP from GDP?

A) citrate synthase
B) isocitrate dehydrogenase
C) malate dehydrogenase
D) succinate-CoA synthetase
E) succinate dehydrogenase

Question 9

A 5-year-old child was rushed to emergency room after accidentally consuming fluoroacetate, a known inhibitor of TCA cycle. Which of the following enzymes is inhibited by fluoroacetate?

A) aconitase
B) citrate synthase
C) isocitrate dehydrogenase
D) malate dehydrogenase
E) succinate dehydrogenase

Question 10

A 56-year-old chronic alcoholic has been brought to the emergency room in a semiconscious state. Blood biochemistry reveals hypoglycemia with a blood glucose level of 45 mg/dL. Which of the following intermediates of TCA cycle can be directly converted to phosphoenolpyruvate to trigger the pathway of gluconeogenesis?

A) α-ketoglutarate
B) malate
C) oxaloacetate
D) pyruvate
E) succinate

Question 11

Anaplerotic reactions are those that result in replenishing intermediates in the TCA cycle. Which of the following enzymes catalyzes an anaplerotic reaction?

A) citrate synthase
B) malate dehydrogenase
C) pyruvate carboxylase
D) pyruvate kinase
E) succinyl-CoA synthetase

Question 12

Oxaloacetate, uniformly labeled with radioactive carbon, reacts with glutamate using transaminase and pyridoxal phosphate. Which of the following percentages of the original radioactivity will be found in 2-oxoglutarate (α-ketoglutarate) formed in this reaction?

A) 0%
B) 25%
C) 50%
D) 75%
E) 100%

Question 13

Energy made available for useful work from metabolism can be represented as the number of moles of ATP, reduced flavoproteins, and reduced pyridine nucleotides that are formed. How many moles of NADH are formed during the conversion of 1 mole of citrate to 1 mole of oxaloacetate and 2 moles of CO₂?

A) 2
B) 3
C) 6
D) 8
E) 12

Question 14

There is no net synthesis of 4-carbon precursors of glucose during the metabolic breakdown of acetyl-CoA in the TCA cycle because of which of the following reason?

A) insufficient NADH for gluconeogenesis is produced in the mitochondrial matrix during oxidation-reduction reactions of the cycle
B) the mitochondrial membrane is impermeable to oxaloacetate which is trapped in the matrix
C) oxidative decarboxylation reactions prevent oxaloacetate production by producing allosteric inhibitors
D) 2 moles of CO₂ are released during each circuit of the cycle

Question 15

Regeneration of which of the following participants in the TCA cycle is dependent on the presence of oxygen?

A) ADP
B) citrate
C) α-ketoglutarate
D) NAD⁺
E) succinate

Question 16

Which of the following best describes why the GTP produced in the conversion of succinyl-CoA to succinate in the TCA cycle is equivalent to ATP?

A) amino group on the C-2 position of GTP can be transferred to the C-6 position to form ATP
B) free energy of hydrolysis of the g-phosphate of GTP is equivalent to that of ATP
C) GTP is used in biosynthetic pathways such as protein synthesis
D) salvage pathway involving phosphoribosylpyrophosphate (PRPP) can be used to regenerate GTP

Question 17

The equilibrium constant for the reaction catalyzed by malate dehydrogenase (malate + NAD⁺ ↔ oxaloacetate + NADH + H⁺) is 10−4. However, in vivo, the production of oxaloacetate is favored because of which of the following?

A) the buildup of malate results in the formation of succinate
B) malate leaves the mitochondrial matrix by a symport carrier along with phosphate
C) oxaloacetate cannot cross the mitochondrial membrane and is trapped in the matrix
D) oxaloacetate is removed by citrate synthas

Question 18

Which of the following CoA derivatives serves the dual function of channeling carbon units into the TCA cycle for oxidative catabolism and acting as a precursor for lipid biosynthesis?

A) acetoacetyl-CoA
B) acetyl-CoA
C) HMG-CoA
D) malonyl-CoA
E) propionyl-CoA