During prolonged fasting, hepatic fatty acid oxidation increases dramatically. The rate-limiting step of mitochondrial beta-oxidation entry is regulated by malonyl-CoA levels. In the fasted state, which metabolic change correctly describes this regulatory mechanism?

• A Malonyl-CoA rises, allosterically activating carnitine palmitoyl transferase-I (CPT-I)
• B Malonyl-CoA rises due to glucagon activation of acetyl-CoA carboxylase
• C Malonyl-CoA directly activates beta-oxidation enzymes in the mitochondrial matrix
• D Malonyl-CoA falls due to low acetyl-CoA carboxylase activity, relieving CPT-I inhibition and allowing long-chain acyl-CoA transport into mitochondria ✓

Explanation

Malonyl-CoA is the first committed intermediate of fatty acid synthesis, produced by acetyl-CoA carboxylase (ACC). In the fasted state, glucagon-driven PKA phosphorylates and inactivates ACC, lowering malonyl-CoA levels. Since malonyl-CoA is a potent allosteric inhibitor of CPT-I (the outer mitochondrial membrane transporter of long-chain acyl groups as acylcarnitines), its fall relieves this inhibition, enabling fatty acid import into the mitochondrial matrix for beta-oxidation. This elegantly prevents simultaneous fatty acid synthesis and oxidation in hepatocytes.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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