Malonyl-CoA acts as a metabolic signal that coordinates fatty acid synthesis and oxidation. How does malonyl-CoA prevent futile cycling during active fatty acid synthesis?

• A It directly inhibits acetyl-CoA carboxylase, halting further fatty acid chain elongation
• B It allosterically inhibits carnitine palmitoyl transferase I (CPT-I), preventing long-chain fatty acyl-CoA import into mitochondria ✓
• C It activates malonyl-CoA decarboxylase, regenerating acetyl-CoA for the TCA cycle
• D It inhibits fatty acid synthase (FAS) by competing with the pantetheine arm of ACP

Explanation

During active fatty acid synthesis in the fed state, high malonyl-CoA levels allosterically inhibit CPT-I (carnitine palmitoyl transferase I), the enzyme that transfers long-chain acyl groups from acyl-CoA to carnitine for mitochondrial import. By blocking CPT-I, malonyl-CoA prevents newly synthesized fatty acids from immediately entering beta-oxidation, avoiding a futile cycle. This reciprocal regulation ensures that synthesis and oxidation do not run simultaneously. In fasting, glucagon suppresses acetyl-CoA carboxylase (reducing malonyl-CoA), disinhibiting CPT-I and promoting beta-oxidation.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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