A student reads that ketone bodies serve as an important fuel for the brain during prolonged starvation. Which of the following correctly describes the rate-limiting step in ketogenesis in the liver?
- A Formation of HMG-CoA by HMG-CoA synthase ✓
- B Condensation of two molecules of acetyl-CoA by thiolase
- C Cleavage of HMG-CoA by HMG-CoA lyase to acetoacetate and acetyl-CoA
- D Reduction of acetoacetate to beta-hydroxybutyrate by beta-hydroxybutyrate dehydrogenase
Correct answer: A. Formation of HMG-CoA by HMG-CoA synthase
Explanation
The rate-limiting step in hepatic ketogenesis is the condensation of acetoacetyl-CoA with acetyl-CoA to form HMG-CoA, catalyzed by mitochondrial HMG-CoA synthase. This enzyme is induced during starvation and high-fat feeding. HMG-CoA lyase then cleaves HMG-CoA to acetoacetate and acetyl-CoA; the lyase step is not rate-limiting. Note that cytosolic HMG-CoA synthase participates in cholesterol synthesis, not ketogenesis.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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