TCA Cycle—Identify the First Isolated Intermediate What is the first stable intermediate formed when acetyl-CoA enters the tricarboxylic acid (TCA) cycle?

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:

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