Part 5 — Tricarboxylic Acid Cycle (Krebs Cycle) (25 MCQs)

Part 5 — Tricarboxylic Acid Cycle (Krebs Cycle) (25 MCQs)

1. Which enzyme catalyzes the condensation of acetyl-CoA and oxaloacetate to form citrate?
   A. Aconitase
   B. Citrate synthase
   C. Isocitrate dehydrogenase
   D. Succinate dehydrogenase
   Answer: B. Citrate synthase
   Explanation:

• A: Converts citrate to isocitrate via cis-aconitate.

• B (Correct): Citrate synthase catalyzes acetyl-CoA + OAA → citrate.

• C/D: Later enzymes in cycle.

2. In one turn of the TCA cycle (one acetyl-CoA), how many NADH and FADH₂ molecules are produced?
   A. 3 NADH and 1 FADH₂
   B. 2 NADH and 2 FADH₂
   C. 1 NADH and 1 FADH₂
   D. 4 NADH and 0 FADH₂
   Answer: A. 3 NADH and 1 FADH₂
   Explanation:

• A (Correct): Isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, and malate dehydrogenase produce NADH (3 total); succinate dehydrogenase yields FADH₂ (1).

• B/C/D: Incorrect stoichiometry.

3. Which step in the TCA cycle produces GTP (or ATP in some organisms) by substrate-level phosphorylation?
   A. Succinyl-CoA → Succinate (succinyl-CoA synthetase)
   B. Isocitrate → α-ketoglutarate
   C. Fumarate → Malate
   D. Citrate → Isocitrate
   Answer: A. Succinyl-CoA → Succinate (succinyl-CoA synthetase)
   Explanation:

• A (Correct): Succinyl-CoA synthetase catalyzes GDP + Pi → GTP (or ADP → ATP in some).

• B/C/D: Other reactions produce NADH or FADH₂ or are isomerizations.

4. Which enzyme is membrane-bound as part of both the TCA cycle and the electron transport chain?
   A. Citrate synthase
   B. Succinate dehydrogenase
   C. Malate dehydrogenase
   D. Aconitase
   Answer: B. Succinate dehydrogenase
   Explanation:

• A/C/D: Soluble matrix enzymes.

• B (Correct): Succinate dehydrogenase (complex II) is an inner mitochondrial membrane enzyme linking TCA to ETS.

5. The TCA cycle is amphibolic. This means:
   A. It only provides energy.
   B. It serves both catabolic (energy-yielding) and anabolic (biosynthetic) roles.
   C. It runs only in water.
   D. It is inhibited by O₂.
   Answer: B. It serves both catabolic (energy-yielding) and anabolic (biosynthetic) roles.
   Explanation:

• A/C/D: Incorrect.

• B (Correct): TCA provides energy (NADH/FADH₂) and intermediates for biosynthesis (e.g., amino acids, heme, glucose via anaplerotic reactions).

6. Which of these TCA intermediates is a major source of carbon skeletons for amino acid biosynthesis (e.g., aspartate)?
   A. Succinate
   B. Oxaloacetate (OAA)
   C. Citrate only
   D. Acetyl-CoA only
   Answer: B. Oxaloacetate (OAA)
   Explanation:

• A/C/D: Other roles exist, but OAA transamination yields aspartate and other derivatives.

• B (Correct): OAA is transaminated to aspartate, precursor for many amino acids and nucleotides.

7. Which TCA enzyme catalyzes an oxidative decarboxylation yielding NADH and CO₂ from isocitrate?
   A. Aconitase
   B. Isocitrate dehydrogenase
   C. α-Ketoglutarate dehydrogenase
   D. Malate dehydrogenase
   Answer: B. Isocitrate dehydrogenase
   Explanation:

• A: Isomerizes citrate to isocitrate.

• B (Correct): Isocitrate dehydrogenase converts isocitrate → α-ketoglutarate + CO₂ + NADH.

• C: Also oxidative decarboxylation but acts on α-ketoglutarate.

• D: Oxidizes malate to OAA (NADH), no CO₂.

8. Which TCA enzyme forms succinate from succinyl-CoA and produces GTP (or ATP)?
   A. Succinate dehydrogenase
   B. Succinyl-CoA synthetase (succinate thiokinase)
   C. Fumarase
   D. Citrate synthase
   Answer: B. Succinyl-CoA synthetase (succinate thiokinase)
   Explanation:

• A: Oxidizes succinate to fumarate producing FADH₂.

• B (Correct): Converts succinyl-CoA → succinate with substrate-level phosphorylation forming GTP.

• C/D: Other steps.

9. Which TCA intermediate can be converted to malate by fumarase?
   A. Succinate
   B. Fumarate
   C. Citrate
   D. α-Ketoglutarate
   Answer: B. Fumarate
   Explanation:

• A: Succinate is converted to fumarate by SDH first.

• B (Correct): Fumarase hydrates fumarate to malate.

• C/D: Not correct.

10. Which cofactor is essential for α-ketoglutarate dehydrogenase activity (similar to PDH)?
    A. Biotin only
    B. TPP (thiamine pyrophosphate) and lipoamide and FAD and NAD⁺ and CoA — similar to PDH complex
    C. Vitamin C only
    D. NADPH only
    Answer: B. TPP (thiamine pyrophosphate) and lipoamide and FAD and NAD⁺ and CoA
    Explanation:

• A/C/D: Incomplete/incorrect.

• B (Correct): α-KGDH is multienzyme complex requiring similar cofactors as PDH.

11. Which of the following is NOT anaplerotic (filling up TCA intermediates)?
    A. Pyruvate carboxylase converting pyruvate to OAA
    B. Transamination of amino acids to form TCA intermediates
    C. Removal of citrate for fatty acid synthesis (cataplerotic)
    D. Conversion of PEP to oxaloacetate by PEP carboxylase
    Answer: C. Removal of citrate for fatty acid synthesis (cataplerotic)
    Explanation:

• A/B/D: Anaplerotic reactions replenish TCA intermediates.

• C (Correct): Removing citrate is cataplerotic (drains intermediates for biosynthesis), not anaplerotic.

12. During rapid biosynthesis, what happens to TCA intermediates?
    A. They remain constant in amount.
    B. Some intermediates are drained off for biosynthetic reactions and must be replenished.
    C. They are all converted to acetyl-CoA.
    D. They are excreted.
    Answer: B. Some intermediates are drained off for biosynthetic reactions and must be replenished.
    Explanation:

• B (Correct): Intermediates used for amino acid, nucleotide, and lipid synthesis require anaplerotic reactions to maintain TCA function.

• A/C/D: Incorrect.

13. Which TCA cycle enzyme is inhibited by high levels of ATP and NADH?
    A. Succinate dehydrogenase
    B. Isocitrate dehydrogenase and α-ketoglutarate dehydrogenase (both regulated)
    C. Aconitase only
    D. None are regulated
    Answer: B. Isocitrate dehydrogenase and α-ketoglutarate dehydrogenase (both regulated)
    Explanation:

• A/C/D: Not complete answer.

• B (Correct): These enzymes are inhibited by high energy charge (ATP, NADH) to downregulate TCA.

14. Which statement is true about citrate in the cytosol?
    A. It is converted to acetyl-CoA and OAA by ATP citrate lyase for fatty acid synthesis.
    B. It directly enters ETS.
    C. It is a final product excreted by the cell.
    D. It serves no metabolic role in cytosol.
    Answer: A. It is converted to acetyl-CoA and OAA by ATP citrate lyase for fatty acid synthesis.
    Explanation:

• A (Correct): Citrate exported to cytosol is cleaved by ATP-citrate lyase to provide acetyl-CoA for lipogenesis.

• B/C/D: Incorrect.

15. Which molecule links the TCA cycle to the electron transport chain directly?
    A. NADH and FADH₂ generated in TCA feed electrons to ETS.
    B. ATP production in cytosol only.
    C. Pyruvate only.
    D. Oxygen in cytosol.
    Answer: A. NADH and FADH₂ generated in TCA feed electrons to ETS.
    Explanation:

• A (Correct): Reduced carriers supply electrons to ETS complexes.

• B/C/D: Not direct links.

16. Which TCA enzyme catalyzes the final step to regenerate oxaloacetate?
    A. Malate dehydrogenase (malate → oxaloacetate)
    B. Citrate synthase
    C. Succinyl-CoA synthetase
    D. Aconitase
    Answer: A. Malate dehydrogenase (malate → oxaloacetate)
    Explanation:

• A (Correct): Malate dehydrogenase oxidizes malate to OAA producing NADH.

• B/C/D: Other steps.

17. Which of these TCA intermediates participates directly in gluconeogenesis via conversion to oxaloacetate?
    A. Succinate
    B. Malate (can be converted to OAA and exported for gluconeogenesis)
    C. Acetyl-CoA
    D. Citrate only
    Answer: B. Malate
    Explanation:

• A/C/D: Succinate can lead to malate but malate is directly converted to OAA and via PEP carboxykinase to PEP in gluconeogenesis; acetyl-CoA cannot be converted to glucose directly (in animals). In plants and via glyoxylate cycle, acetyl-CoA can feed gluconeogenesis in seeds.

• B (Correct): Malate is key in shuttle and gluconeogenesis.

18. Which enzyme of TCA is an integral membrane protein of the inner mitochondrial membrane?
    A. Succinate dehydrogenase
    B. Aconitase
    C. Malate dehydrogenase
    D. Citrate synthase
    Answer: A. Succinate dehydrogenase
    Explanation:

• A (Correct): SDH (Complex II) is embedded in the inner mitochondrial membrane and links TCA to ETS.

• B/C/D: Matrix enzymes.

19. Which coenzyme is regenerated in the TCA cycle by oxidation of FADH₂ in the ETS?
    A. NAD⁺
    B. FAD (regenerated from FADH₂ by complex II/III onward)
    C. CoA
    D. ATP
    Answer: B. FAD (regenerated from FADH₂ by ETS)
    Explanation:

• A: NAD⁺ is regenerated by NADH oxidation in ETS, but this question asks specifically FADH₂ oxidation regenerating FAD.

• B (Correct): FADH₂ transfers electrons to ETS via succinate dehydrogenase and returns to FAD.

• C/D: Not relevant.

20. Which TCA intermediate is directly involved in heme biosynthesis?
    A. Succinate + glycine → δ-aminolevulinic acid (precursor)
    B. Oxaloacetate directly → heme
    C. Citrate only → heme
    D. Malate directly → heme
    Answer: A. Succinate + glycine → δ-aminolevulinic acid (precursor)
    Explanation:

• A (Correct): Succinyl-CoA condenses with glycine to form ALA, the first step in porphyrin/heme biosynthesis.

• B/C/D: Incorrect.

21. Which of the following is a rate-limiting enzyme of the TCA cycle?
    A. Citrate synthase only
    B. Isocitrate dehydrogenase (sensitive to ATP/NADH)
    C. Malate dehydrogenase only
    D. All enzymes are unregulated
    Answer: B. Isocitrate dehydrogenase (sensitive to ATP/NADH)
    Explanation:

• A/C/D: Partial/incorrect.

• B (Correct): Isocitrate dehydrogenase is tightly regulated and a key control point modulated by ADP/ATP/NADH.

22. Which of the following will happen when there is a block in TCA cycle at α-ketoglutarate dehydrogenase?
    A. Accumulation of α-ketoglutarate and reduced production of NADH and succinyl-CoA-derived products
    B. Increased citrate synthase activity automatically
    C. Immediate halt of glycolysis
    D. Instant increase in OAA levels
    Answer: A. Accumulation of α-ketoglutarate and reduced production of NADH and succinyl-CoA-derived products
    Explanation:

• A (Correct): Block leads to accumulation upstream and depletion downstream (succinyl-CoA etc.).

• B/C/D: Not necessarily immediate or correct effects.

23. Which TCA intermediate is involved in the urea cycle in animals (not plants) by transamination?
    A. Citrate
    B. α-Ketoglutarate
    C. Oxaloacetate (through aspartate)
    D. Succinate
    Answer: C. Oxaloacetate (through aspartate)
    Explanation:

• A/B/D: Other roles.

• C (Correct): Oxaloacetate transaminates to aspartate; aspartate provides one nitrogen in urea cycle (animals). Plants don’t make urea but the concept links TCA to nitrogen metabolism.

24. Which of the following describes the energetic output from one turn of TCA in terms of high-energy carriers?
    A. 3 NADH, 1 FADH₂, 1 GTP (or ATP) and 2 CO₂
    B. 2 NADH, 2 FADH₂, 3 ATP
    C. 4 FADH₂ only
    D. 1 NADH only
    Answer: A. 3 NADH, 1 FADH₂, 1 GTP (or ATP) and 2 CO₂
    Explanation:

• A (Correct): Standard yield per acetyl-CoA.

• B/C/D: Incorrect.

25. Which TCA cycle intermediate directly provides carbon skeleton for the synthesis of glutamate via transamination?
    A. Succinate
    B. α-Ketoglutarate
    C. Citrate
    D. Malate
    Answer: B. α-Ketoglutarate
    Explanation:

• A/C/D: Not direct precursors for glutamate.

• B (Correct): α-KG is aminated to glutamate; central to nitrogen assimilation and amino acid synthesis.

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