In prolonged starvation, the liver produces ketone bodies that serve as alternative fuel for the brain. The rate-limiting regulated enzyme for ketogenesis is:

• A HMG-CoA synthase (mitochondrial isoform) ✓
• B Thiolase (acetyl-CoA acetyltransferase)
• C HMG-CoA lyase
• D Beta-hydroxybutyrate dehydrogenase

Explanation

The mitochondrial HMG-CoA synthase (distinct from the cytosolic isoform involved in cholesterol synthesis) catalyzes the condensation of acetyl-CoA with acetoacetyl-CoA to form HMG-CoA — the committed rate-limiting step of ketogenesis. Its expression is induced by glucagon (via CREB), free fatty acids, and acetyl-CoA during fasting; it is inhibited by succinyl-CoA (indicating adequate TCA cycle activity and energy). Thiolase and HMG-CoA lyase are downstream steps. The cytosolic HMG-CoA synthase produces HMG-CoA for cholesterol synthesis, which is regulated by statins.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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