Metabolism: MCQs on Tricarboxylic Acid Cycle (TCA Cycle, Krebs Cycle)

Multiple Choice Questions on Tricarboxylic Acid or TCA Cycle

1) The conversion of pyruvate to acetyl CoA is catalyzed by the enzyme pyruvate dehydrogenase. In this reaction
a) NADPH is oxidized to NADP
b) NADH is oxidized to NAD
c) NADP is reduced to NADPH
d) NAD is reduced to NADH

2) In the tricarboxylic acid cycle, the reaction for the conversion of pyruvate to acetyl CoA is known as
a) Oxidative decarboxylation
b) Oxidative phosphorylation
c) Reductive biosynthesis
d) Reductive decarboxylation

3) Which of the following is false regarding the enzyme pyruvate dehydrogenase?
a) It is a multi-enzyme complex
b) It catalyzes the reversible reaction (conversion of pyruvate to acetyl CoA)
c) The pyruvate dehydrogenase complex is a mitochondrial enzyme
d) It requires thiamine, flavin, and nicotine vitamin co-enzymes

4) Pyruvate dehydrogenase is an important regulatory enzyme that senses the energy status of the cells. Which of the following is NOT the regulator of pyruvate dehydrogenase?
a) Calcium
b) Acetyl CoA
c) ATP
d) Citrate

5) Arsenic binds to the thiol group of lipoic acid and interferes with the activity of enzymes that require lipoic acid as a co-factor. Which of the following enzyme does not require lipoic acid for its activity and NOT directly inhibited by arsenic?
a) Pyruvate dehydrogenase
b) Isocitrate dehydrogenase
c) Malate dehydrogenase
d) Branched-chain amino acid dehydrogenase

6) Citrate synthase is the enzyme that catalyzes the condensation of acetyl CoA and oxaloacetate to citrate. Which of the following is an activator of this enzyme?
a) Succinyl CoA
c) Fatty Acyl CoA
d) ADP

7) Which of the following enzyme catalyzes substrate-level phosphorylation i.e conversion of GDP to GTP?
a) Malate dehydrogenase
b) Fumarase
c) Isocitrate dehydrogenase
d) Succinyl CoA thiokinase

8) In Krebs (TCA) cycle, when two carbon Acetyl CoA is oxidized to CO2, the total yield of ATP is
a) 8
b) 12
c) 14
d) 16

9) Which of the following is not the irreversible reaction of Kreb's cycle?
a) Isocitrate dehydrogenase
b) Alpha-ketoglutarate dehydrogenase
c) Citrate synthase
d) Malate dehydrogenase

10) Which of the following enzyme causes congenital lactic acidosis
a) Isocitrate dehydrogenase
b) Alpha-ketoglutarate dehydrogenase
c) Pyruvate dehydrogenase
d) Malate dehydrogenase

11) Which of the following enzyme of the TCA cycle catalyzes co-reduction of FAD+ to FADH2?
a) Isocitrate dehydrogenase
b) Alpha-ketoglutarate dehydrogenase
c) Succinate Dehydrogenase
d) Malate dehydrogenase

12) TCA cycle is also known as the amphibolic pathway (functions both in oxidative and synthetic processes).
Which of the following is a correct statement regarding the TCA cycle?
a) Alpha-ketoglutarate plays a critical role in amino acid metabolism
b) Oxaloacetate is an intermediate for gluconeogenesis and fatty acid synthesis
c) Succinyl CoA is involved in ketone body metabolism
d) All of the above

13) Which of the following metabolic intermediate activates the TCA cycle?
a) High NADH/NAD ratio
b) High ADP/ATP ratio
c) High Oxaloacetate
d) None of the above

Multiple Choice Answers

1- d) NAD is reduced to NADH
When pyruvate enters the mitochondria, it is converted into acetyl-CoA by the pyruvate dehydrogenase complex, as I mentioned in the previous response. During this conversion, NAD+ (nicotinamide adenine dinucleotide) is reduced to NADH. The reduction of NAD+ to NADH occurs in the following step:
The pyruvate dehydrogenase complex uses the E3 enzyme, dihydrolipoamide dehydrogenase, which utilizes the cofactor FAD (flavin adenine dinucleotide), to catalyze the transfer of electrons from the reduced form of lipoamide to NAD+, resulting in the formation of NADH.

2- a) Oxidative decarboxylation
The oxidative decarboxylation of pyruvate refers to the conversion of pyruvate, a three-carbon molecule, into acetyl-CoA, a two-carbon molecule. This process occurs in the mitochondria and is catalyzed by the pyruvate dehydrogenase complex. It is a key step in cellular respiration and links the end product of glycolysis with the citric acid cycle.

3-b) It catalyzes the reversible reaction (conversion of pyruvate to acetyl CoA)

4-d) Citrate
PDH is regulated by allosteric effectors that can either activate or inhibit its activity. For example, high levels of ATP, NADH, and acetyl-CoA (indicative of ample energy supply) can inhibit PDH, while high levels of ADP, NAD+, and CoA (indicative of energy demand) can activate PDH.
Calcium ions (Ca2+) are an important activator of PDP, so increased intracellular calcium levels can stimulate PDH activation.

5-c) Malate dehydrogenase
Arsenic binds to Pyruvate dehydrogenase, Isocitrate dehydrogenase & Branched-chain amino acid dehydrogenase.

 6-d) ADP
Citrate synthase is sensitive to the energy demands of the cell, and the ratio of ATP to ADP plays a crucial role in regulating its activity. When the energy demand is high, ADP levels increase while ATP levels decrease. This increase in the ADP/ATP ratio can relieve the inhibitory effect of high ATP levels on citrate synthase, leading to increased enzyme activity. 

7-d) Succinyl CoA thiokinase
Succinyl-CoA thiokinase, also known as succinyl-CoA synthetase, is an enzyme involved in the tricarboxylic acid (TCA) cycle, specifically in the conversion of succinyl-CoA to succinate. This step is an important part of energy metabolism as it generates high-energy phosphate bonds and produces GTP.

8-b) 12

9-d) Malate dehydrogenase
The irreversible steps of the TCA cycle are:
Citrate Synthase: The conversion of acetyl-CoA and oxaloacetate to citrate is catalyzed by the enzyme citrate synthase. This step is highly exergonic and irreversible, ensuring that once citrate is formed, it proceeds through the cycle and prevents the backflow of intermediates.
Isocitrate Dehydrogenase: The conversion of isocitrate to alpha-ketoglutarate is catalyzed by the enzyme isocitrate dehydrogenase. This reaction involves the oxidative decarboxylation of isocitrate and the generation of NADH. It is an irreversible step and a key regulatory point in the TCA cycle.
alpha-Ketoglutarate Dehydrogenase Complex: The conversion of alpha-ketoglutarate to succinyl-CoA is catalyzed by the alpha-ketoglutarate dehydrogenase complex, similar to the pyruvate dehydrogenase complex. This step involves decarboxylation and the generation of NADH. It is an irreversible and regulated step in the cycle.

10-c) Pyruvate dehydrogenase
Pyruvate Dehydrogenase Complex Deficiency: Pyruvate dehydrogenase complex (PDC) deficiency is a disorder that impairs the function of the enzyme complex responsible for converting pyruvate to acetyl-CoA, a key step in cellular energy production. Mutations in the genes encoding the components of PDC can lead to the accumulation of pyruvate and lactate, resulting in congenital lactic acidosis.

11-c) Succinate Dehydrogenase
Succinate dehydrogenase, also known as complex II, is an enzyme complex located in the inner mitochondrial membrane. It catalyzes the conversion of succinate to fumarate while simultaneously transferring electrons to the electron transport chain (ETC). During this process, FAD+ is reduced to FADH2.
The reaction can be summarized as follows:
Succinate + FAD+ + CoQ (ubiquinone) → Fumarate + FADH2 + CoQH2
The electrons extracted from succinate are transferred to FAD+ to form FADH2. The FADH2 produced in this reaction then donates its electrons to the ETC, where they participate in the production of ATP through oxidative phosphorylation.

12-d) All of the above
The TCA cycle is also an amphibolic pathway because it provides intermediate metabolites that are used for various anabolic pathways. Some of the intermediates, such as citrate, α-ketoglutarate, and oxaloacetate, serve as precursors for the biosynthesis of amino acids, nucleotides, and other biomolecules. These intermediates can be diverted from the TCA cycle to support the synthesis of macromolecules and cellular components.

13-c) High Oxaloacetate
Oxaloacetate is an important intermediate in the TCA cycle. When oxaloacetate levels are high, it can stimulate and enhance the flux through the TCA cycle. This increased TCA cycle activity leads to increased production of reducing equivalents (NADH and FADH2) and ATP.