Citric acid cycle – significance MCQs With Answer

Introduction:

The citric acid cycle, also known as the Krebs cycle or TCA cycle, is a central metabolic pathway in cellular respiration critical for energy production and biosynthesis. For B. Pharm students, understanding the citric acid cycle significance is essential for pharmacology, drug metabolism, and clinical biochemistry. Key topics include enzyme regulation, ATP and reducing equivalent yield (NADH, FADH2), intermediates like citrate and α-ketoglutarate, and links to anaplerotic reactions and drug action (e.g., fluorocitrate). This guide offers a concise, exam-oriented review with focus on metabolism, enzyme cofactors, regulation, and clinical relevance. Now let’s test your knowledge with 50 MCQs on this topic.

Q1. Which cellular compartment houses the citric acid cycle in eukaryotic cells?

• Cytosol
• Endoplasmic reticulum
• Mitochondrial matrix
• Intermembrane space of mitochondria

Correct Answer: Mitochondrial matrix

Q2. The citric acid cycle begins with the condensation of acetyl-CoA and which four-carbon molecule?

• Malate
• Oxaloacetate
• Citrate
• Succinyl-CoA

Correct Answer: Oxaloacetate

Q3. Which enzyme catalyzes the first committed step of the citric acid cycle, forming citrate?

• Aconitase
• Citrate synthase
• Isocitrate dehydrogenase
• α-Ketoglutarate dehydrogenase

Correct Answer: Citrate synthase

Q4. Which step in the TCA cycle produces GTP (or ATP) via substrate-level phosphorylation?

• Conversion of isocitrate to α-ketoglutarate
• Conversion of succinyl-CoA to succinate
• Conversion of fumarate to malate
• Conversion of citrate to isocitrate

Correct Answer: Conversion of succinyl-CoA to succinate

Q5. How many molecules of NADH are produced per acetyl-CoA oxidized in one turn of the citric acid cycle?

• 1
• 2
• 3
• 4

Correct Answer: 3

Q6. Which TCA cycle enzyme is also an integral component of the electron transport chain (Complex II)?

• Succinate dehydrogenase
• Malate dehydrogenase
• Fumarase
• α-Ketoglutarate dehydrogenase

Correct Answer: Succinate dehydrogenase

Q7. The conversion of α-ketoglutarate to succinyl-CoA requires which set of cofactors?

• Biotin, ATP
• TPP, lipoamide, FAD, NAD+, CoA
• FMN, heme, Cu2+
• Vitamin C and zinc

Correct Answer: TPP, lipoamide, FAD, NAD+, CoA

Q8. Which vitamin is a precursor for NAD+, an essential cofactor in the TCA cycle dehydrogenase reactions?

• Vitamin B1 (thiamine)
• Vitamin B2 (riboflavin)
• Vitamin B3 (niacin)
• Vitamin B5 (pantothenic acid)

Correct Answer: Vitamin B3 (niacin)

Q9. Fluoroacetate poisoning inhibits the TCA cycle by forming fluorocitrate that inhibits which enzyme?

• Citrate synthase
• Aconitase
• Isocitrate dehydrogenase
• Malate dehydrogenase

Correct Answer: Aconitase

Q10. Which reaction in the TCA cycle is a dehydration followed by hydration catalyzed by aconitase?

• Citrate to isocitrate via cis-aconitate
• Succinate to fumarate
• Fumarate to malate
• Malate to oxaloacetate

Correct Answer: Citrate to isocitrate via cis-aconitate

Q11. The TCA cycle is described as amphibolic. What does amphibolic mean in this context?

• Operates only under anaerobic conditions
• Functions in both catabolism and anabolism
• Is only involved in energy production
• Occurs exclusively in bacteria

Correct Answer: Functions in both catabolism and anabolism

Q12. Which TCA intermediate is a key precursor for gluconeogenesis and transamination reactions?

• Citrate
• Oxaloacetate
• Succinate
• Fumarate

Correct Answer: Oxaloacetate

Q13. Which enzyme catalyzes the oxidation of isocitrate and is a major regulatory point of the TCA cycle?

• Isocitrate dehydrogenase
• Citrate lyase
• Malate synthase
• Succinyl-CoA synthetase

Correct Answer: Isocitrate dehydrogenase

Q14. Which cofactors are required by succinate dehydrogenase for its catalytic activity?

• FAD and iron–sulfur clusters
• NAD+ and TPP
• Biotin and ATP
• PLP and magnesium

Correct Answer: FAD and iron–sulfur clusters

Q15. How many ATP (or ATP equivalents) are theoretically produced per acetyl-CoA oxidized in the TCA cycle when considering oxidative phosphorylation yields?

• 1 ATP equivalent
• 3 ATP equivalents
• 10 ATP equivalents
• 25 ATP equivalents

Correct Answer: 10 ATP equivalents

Q16. Which enzyme regenerates oxaloacetate from malate while producing NADH?

• Malate dehydrogenase
• Fumarase
• Pyruvate dehydrogenase
• Citrate synthase

Correct Answer: Malate dehydrogenase

Q17. The pyruvate dehydrogenase complex links glycolysis to the TCA cycle by converting pyruvate to what molecule?

• Oxaloacetate
• Acetyl-CoA
• Lactate
• Alanine

Correct Answer: Acetyl-CoA

Q18. Which of the following is a major allosteric activator of isocitrate dehydrogenase?

• ATP
• NADH
• ADP
• Citrate

Correct Answer: ADP

Q19. Which anaplerotic enzyme converts pyruvate to oxaloacetate, replenishing TCA intermediates?

• Pyruvate dehydrogenase
• Pyruvate carboxylase
• Phosphoenolpyruvate carboxykinase
• Lactate dehydrogenase

Correct Answer: Pyruvate carboxylase

Q20. α-Ketoglutarate is a precursor for the synthesis of which important amino acid via transamination?

• Glutamate
• Serine
• Phenylalanine
• Glycine

Correct Answer: Glutamate

Q21. Which intermediate is exported from mitochondria as citrate to serve as a substrate for cytosolic fatty acid synthesis?

• Malate
• Citrate
• Succinate
• Fumarate

Correct Answer: Citrate

Q22. The conversion of succinate to fumarate is catalyzed by which type of enzyme?

• Dehydrogenase that reduces NAD+
• Dehydrogenase that reduces FAD
• Hydratase using water addition
• Ligase forming a new C–C bond

Correct Answer: Dehydrogenase that reduces FAD

Q23. Which TCA cycle enzyme requires manganese or magnesium as a cofactor for activity?

• Citrate synthase
• Isocitrate dehydrogenase
• Fumarase
• Malate dehydrogenase

Correct Answer: Isocitrate dehydrogenase

Q24. Which metabolite accumulation indicates a defect in succinate dehydrogenase in clinical diagnoses?

• High plasma citrate
• High succinate
• Low fumarate
• Increased oxaloacetate

Correct Answer: High succinate

Q25. Which reaction directly produces FADH2 in the TCA cycle?

• Isocitrate to α-ketoglutarate
• α-Ketoglutarate to succinyl-CoA
• Succinate to fumarate
• Malate to oxaloacetate

Correct Answer: Succinate to fumarate

Q26. What is the effect of high NADH/NAD+ ratio on the activity of the TCA cycle?

• Stimulates TCA cycle enzymes
• Inhibits NAD+-dependent dehydrogenases and slows cycle
• Increases citrate export for lipid synthesis only
• Has no effect on the TCA cycle

Correct Answer: Inhibits NAD+-dependent dehydrogenases and slows cycle

Q27. Which TCA intermediate can be transaminated to form oxaloacetate’s amino acid derivative aspartate?

• Glutamate
• Malate
• Oxaloacetate directly transaminates to aspartate
• α-Ketoglutarate

Correct Answer: Oxaloacetate directly transaminates to aspartate

Q28. Which drug or toxin classically inhibits the pyruvate dehydrogenase complex, indirectly affecting the TCA cycle?

• Cyanide
• Organophosphates
• Arsenic compounds (arsenite)
• Beta-lactam antibiotics

Correct Answer: Arsenic compounds (arsenite)

Q29. How many carbon dioxide molecules are released per acetyl-CoA oxidized in the TCA cycle?

• 0
• 1
• 2
• 3

Correct Answer: 2

Q30. Which enzyme in the TCA cycle is inhibited by high concentrations of ATP as feedback regulation?

• Succinate dehydrogenase
• Citrate synthase and isocitrate dehydrogenase
• Fumarase
• Malate dehydrogenase

Correct Answer: Citrate synthase and isocitrate dehydrogenase

Q31. The malate-aspartate shuttle is important for transferring what from the cytosol into the mitochondrial matrix?

• ATP directly
• NADH reducing equivalents
• Acetyl-CoA molecules
• Oxygen molecules

Correct Answer: NADH reducing equivalents

Q32. Which intermediate links the TCA cycle to heme synthesis?

• Succinyl-CoA
• Citrate
• Fumarate
• Malate

Correct Answer: Succinyl-CoA

Q33. Which enzyme catalyzes the reversible hydration of fumarate to malate?

• Fumarase (fumarate hydratase)
• Malate dehydrogenase
• Fumarate reductase
• Hydratase III

Correct Answer: Fumarase (fumarate hydratase)

Q34. During fasting, increased fatty acid oxidation provides acetyl-CoA to the TCA cycle; what can excess acetyl-CoA lead to when oxaloacetate is depleted?

• Enhanced TCA flux and reduced ketone bodies
• Ketone body formation (ketogenesis)
• Glucose production by the TCA cycle
• Increased protein synthesis

Correct Answer: Ketone body formation (ketogenesis)

Q35. Which enzyme’s deficiency leads to accumulation of fumarate and is associated with hereditary leiomyomatosis and renal cell cancer?

• Succinate dehydrogenase
• Fumarase (fumarate hydratase)
• Malate dehydrogenase
• Citrate synthase

Correct Answer: Fumarase (fumarate hydratase)

Q36. Which statement best describes the role of citrate in metabolic regulation?

• Citrate inhibits phosphofructokinase-1, reducing glycolysis when citrate is high
• Citrate activates phosphofructokinase-1 to stimulate glycolysis
• Citrate has no regulatory role and is only a TCA intermediate
• Citrate directly converts to glucose in the cytosol

Correct Answer: Citrate inhibits phosphofructokinase-1, reducing glycolysis when citrate is high

Q37. Which coenzyme A (CoA) derivative enters the TCA cycle as a two-carbon unit?

• Succinyl-CoA
• Acetyl-CoA
• Malonyl-CoA
• Propionyl-CoA

Correct Answer: Acetyl-CoA

Q38. Which TCA cycle enzyme is regulated by phosphorylation/dephosphorylation in some tissues (or regulated indirectly via PDH for link to glycolysis)?

• Pyruvate dehydrogenase complex
• Malate dehydrogenase
• Isocitrate dehydrogenase via phosphorylation in bacteria only
• Citrate synthase via phosphorylation

Correct Answer: Pyruvate dehydrogenase complex

Q39. Which metabolic reaction replenishes TCA intermediates from odd-chain fatty acids?

• Conversion of propionyl-CoA to succinyl-CoA
• Conversion of acetyl-CoA to oxaloacetate
• Conversion of malonyl-CoA to succinate
• Beta-oxidation yields only acetyl-CoA and no anaplerotic input

Correct Answer: Conversion of propionyl-CoA to succinyl-CoA

Q40. Which TCA intermediate is transported out of mitochondria and cleaved by ATP-citrate lyase to provide cytosolic acetyl-CoA for fatty acid synthesis?

• Malate
• Citrate
• α-Ketoglutarate
• Oxaloacetate

Correct Answer: Citrate

Q41. In the context of drug interactions, inhibition of which enzyme would most directly reduce cellular NADH generation from the TCA cycle?

• Citrate synthase
• Isocitrate dehydrogenase
• Fumarase
• Phosphofructokinase-1

Correct Answer: Isocitrate dehydrogenase

Q42. Which TCA cycle enzyme catalyzes a decarboxylation reaction producing CO2 and NADH at a rate sensitive to calcium levels in muscle?

• Citrate synthase
• α-Ketoglutarate dehydrogenase
• Succinate dehydrogenase
• Isocitrate dehydrogenase (NAD+ dependent)

Correct Answer: Isocitrate dehydrogenase (NAD+ dependent)

Q43. Which of the following best describes the stoichiometry of the TCA cycle per acetyl-CoA in terms of CO2, NADH, FADH2, and GTP?

• 2 CO2, 3 NADH, 1 FADH2, 1 GTP
• 1 CO2, 2 NADH, 2 FADH2, 0 GTP
• 3 CO2, 1 NADH, 1 FADH2, 1 ATP
• 2 CO2, 2 NADH, 2 FADH2, 2 GTP

Correct Answer: 2 CO2, 3 NADH, 1 FADH2, 1 GTP

Q44. Which intermediate accumulates when there is a block in the conversion of succinyl-CoA to succinate?

• Succinate
• Succinyl-CoA
• Citrate
• Malate

Correct Answer: Succinyl-CoA

Q45. Which enzyme catalyzes a reversible reaction that is near equilibrium under physiological conditions and thus readily participates in shuttle reactions?

• Citrate synthase
• Malate dehydrogenase
• α-Ketoglutarate dehydrogenase
• Citrate lyase

Correct Answer: Malate dehydrogenase

Q46. Which TCA intermediate is involved in the urea cycle via formation of aspartate after transamination?

• α-Ketoglutarate
• Oxaloacetate
• Succinate
• Fumarate

Correct Answer: Oxaloacetate

Q47. Which pharmacological agent uncouples oxidative phosphorylation and indirectly reduces ATP production despite active TCA cycle activity?

• Oligomycin
• Rotenone
• 2,4-Dinitrophenol (DNP)
• Cyanide

Correct Answer: 2,4-Dinitrophenol (DNP)

Q48. Inherited deficiencies in which TCA enzyme can present with neurological symptoms due to impaired energy metabolism?

• Isocitrate dehydrogenase
• α-Ketoglutarate dehydrogenase complex
• Citrate synthase only in liver
• ATP-citrate lyase exclusively

Correct Answer: α-Ketoglutarate dehydrogenase complex

Q49. What role does biotin play in relation to the TCA cycle and anaplerosis?

• Coenzyme for pyruvate carboxylase converting pyruvate to oxaloacetate
• Direct electron carrier in the TCA cycle
• Cofactor for succinate dehydrogenase
• Inhibitor of citrate synthase

Correct Answer: Coenzyme for pyruvate carboxylase converting pyruvate to oxaloacetate

Q50. Which TCA intermediate donates two-carbon fragments for cholesterol and fatty acid synthesis after being exported to the cytosol?

• Malate
• Citrate
• α-Ketoglutarate
• Succinate

Correct Answer: Citrate

G S Sachin

I am a Registered Pharmacist under the Pharmacy Act, 1948, and the founder of PharmacyFreak.com. I hold a Bachelor of Pharmacy degree from Rungta College of Pharmaceutical Science and Research. With a strong academic foundation and practical knowledge, I am committed to providing accurate, easy-to-understand content to support pharmacy students and professionals. My aim is to make complex pharmaceutical concepts accessible and useful for real-world application.

Mail- Sachin@pharmacyfreak.com