TCA Cycle—Identify the First Isolated Intermediate What is the first stable intermediate formed when acetyl-CoA enters the tricarboxylic acid (TCA) cycle?
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ASuccinate
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BFumarate
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CCitrate
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DMalate
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EOxaloacetate
Answer
Correct Answer: Citrate
Explanation
Introduction / Context:The TCA cycle begins when acetyl-CoA condenses with oxaloacetate. Knowing the sequence of intermediates is essential for tracing carbon flow and understanding regulation points in central metabolism.
Given Data / Assumptions:
- Entry substrate: acetyl-CoA (2 carbons).
- Acceptor: oxaloacetate (4 carbons).
- Enzyme: citrate synthase.
Concept / Approach:Citrate synthase catalyzes condensation of acetyl-CoA with oxaloacetate to form citrate (6 carbons) via an intermediate citryl-CoA. Citrate is the first stable and isolable TCA intermediate after entry, preceding isomerization to isocitrate by aconitase.
Step-by-Step Solution:
Combine acetyl-CoA (2C) + oxaloacetate (4C) → citrate (6C).Recognize citrate as the first product after the entry condensation step.Note subsequent steps: citrate → isocitrate via aconitase (not required for this answer).Verification / Alternative check:Enzyme assays for citrate synthase activity and accumulation of citrate in conditions of aconitase inhibition corroborate this sequence.
Why Other Options Are Wrong:
- Succinate, fumarate, malate: later TCA intermediates.
- Oxaloacetate: the acceptor that reacts with acetyl-CoA; not the first product formed after entry.
Common Pitfalls:Confusing oxaloacetate (the acceptor) with citrate (the first product).
Final Answer:Citrate