During prolonged fasting, hepatic ketogenesis rises sharply. The rate-limiting and committed step of ketone body synthesis in the liver mitochondrion is catalyzed by:

• A Acetoacetyl-CoA thiolase
• B HMG-CoA reductase
• C HMG-CoA lyase
• D HMG-CoA synthase (mitochondrial isoform) ✓

Explanation

Mitochondrial HMG-CoA synthase condenses acetoacetyl-CoA with acetyl-CoA to form HMG-CoA; this step is committed to ketogenesis and is induced during fasting. HMG-CoA lyase then cleaves HMG-CoA to acetoacetate, and thiolase forms acetoacetyl-CoA, but neither is rate-limiting. HMG-CoA reductase operates in the cytosol on the cholesterol pathway and is a completely separate gene product.

Reference: Lippincott's Illustrated Reviews: Biochemistry, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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