Carnitine palmitoyl transferase I (CPT-I) is the rate-limiting enzyme for long-chain fatty acid entry into mitochondria for beta-oxidation. In the fed state, which metabolite specifically inhibits CPT-I, thereby preventing futile cycling between fatty acid synthesis and oxidation?
- A Acetyl-CoA
- B Citrate
- C Malonyl-CoA ✓
- D Succinyl-CoA
Correct answer: C. Malonyl-CoA
Explanation
Malonyl-CoA, the first committed intermediate of fatty acid synthesis (produced by acetyl-CoA carboxylase), allosterically inhibits CPT-I on the outer mitochondrial membrane. When fatty acid synthesis is active (fed state), malonyl-CoA levels rise and simultaneously inhibit beta-oxidation entry, preventing a futile cycle. In the fasted or glucagon-stimulated state, AMPK phosphorylates and inactivates acetyl-CoA carboxylase, malonyl-CoA levels fall, and CPT-I is relieved of inhibition.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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