An unresponsive 24-year-old woman with type 1 diabetes is brought to the emergency department with deep sighing respiration and a fruity breath odour. Glucose is 540 mg/dL, pH 7.05, and serum ketones are strongly positive. The rate-limiting enzyme of hepatic ketone body formation in this state is:
- A HMG-CoA reductase
- B Acetyl-CoA carboxylase
- C Mitochondrial HMG-CoA synthase ✓
- D Thiolase
Correct answer: C. Mitochondrial HMG-CoA synthase
Explanation
In insulin deficiency, unrestrained lipolysis floods the liver with fatty acyl-CoA, malonyl-CoA falls, and carnitine shuttle flux rises, diverting acetyl-CoA into ketogenesis. Mitochondrial HMG-CoA synthase catalyses the committed step, condensing acetoacetyl-CoA with acetyl-CoA, and is induced in fasting and diabetes. HMG-CoA reductase is the cholesterol pathway enzyme, acetyl-CoA carboxylase is suppressed here, and thiolase is not rate-limiting.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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