HMG-CoA lyase deficiency presents with hypoketotic hypoglycemia during fasting, similar to MCAD deficiency but differs because it also causes metabolic acidosis with elevated 3-hydroxy-3-methylglutaric acid. HMG-CoA lyase catalyses which reaction?
- A Cleavage of HMG-CoA to acetyl-CoA + acetoacetate (committed step of ketogenesis in liver mitochondria) ✓
- B Condensation of two acetyl-CoA molecules in ketogenesis (liver)
- C Reduction of HMG-CoA to mevalonate in cholesterol synthesis pathway
- D Carboxylation of beta-methylcrotonyl-CoA in leucine catabolism
Explanation
HMG-CoA lyase cleaves 3-hydroxy-3-methylglutaryl-CoA to acetyl-CoA + acetoacetate — the final committed step of hepatic ketogenesis. Its deficiency completely blocks ketone body production. During fasting when glucose is low, the liver cannot produce ketones, and peripheral tissues starve for fuel, causing hypoketotic hypoglycemia. Additionally, HMG-CoA lyase also participates in leucine catabolism (mitochondrial), so its deficiency also impairs leucine degradation, causing accumulation of 3-hydroxy-3-methylglutaric acid (detectable on organic acid profile). HMG-CoA reductase (NOT lyase) produces mevalonate in cholesterol synthesis.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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