During fasting, hepatic ketogenesis rises sharply. The rate-limiting enzyme of hepatic ketone body synthesis, strongly induced by glucagon and suppressed by insulin, is:
- A Cytosolic HMG-CoA synthase
- B HMG-CoA lyase
- C Mitochondrial HMG-CoA synthase ✓
- D Acetoacetyl-CoA thiolase
Correct answer: C. Mitochondrial HMG-CoA synthase
Explanation
Two distinct HMG-CoA synthase isoforms exist: the cytosolic enzyme feeds cholesterol biosynthesis, while the mitochondrial enzyme condenses acetyl-CoA with acetoacetyl-CoA to form HMG-CoA, the committed and rate-limiting step of ketogenesis. Its gene is upregulated by cAMP-mediated glucagon signaling and fatty acid oxidation products, and downregulated by insulin. HMG-CoA lyase subsequently cleaves HMG-CoA to acetoacetate but is not the regulated control point, and acetoacetyl-CoA thiolase operates upstream in a near-equilibrium reaction.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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