In fatty acid synthesis, each two-carbon addition requires NADPH. Malonyl-CoA, the two-carbon donor, is formed from acetyl-CoA and CO2. The rate-limiting enzyme acetyl-CoA carboxylase is allosterically regulated. Which combination correctly identifies its allosteric activator and inhibitor?

• A Activated by palmitoyl-CoA; inhibited by citrate
• B Activated by citrate; inhibited by palmitoyl-CoA ✓
• C Activated by AMP; inhibited by ADP
• D Activated by malonyl-CoA; inhibited by acetyl-CoA

Explanation

Acetyl-CoA carboxylase (ACC) is the rate-limiting enzyme of fatty acid synthesis. Citrate — which accumulates when the TCA cycle is saturated — allosterically activates ACC by inducing polymerization to its active filamentous form, signalling that excess acetyl-CoA is available for lipogenesis. Palmitoyl-CoA, the long-chain end product, feedback-inhibits ACC to prevent futile cycling. Additionally, glucagon/epinephrine activate AMPK which phosphorylates and inactivates ACC, while insulin activates a phosphatase that dephosphorylates and activates ACC.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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