Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is the most common inherited fatty acid oxidation disorder. A child presents with hypoketotic hypoglycemia during a febrile illness. Why is ketogenesis specifically impaired despite increased fatty acid mobilization?
- A MCAD deficiency blocks beta-oxidation of C6-C12 fatty acids; acetyl-CoA generation is insufficient for ketogenesis ✓
- B The enzyme HMG-CoA synthase is competitively inhibited by medium-chain acyl-CoA esters
- C Acylcarnitine esters of medium-chain fatty acids inhibit CPT-I, blocking all long-chain fatty acid entry
- D Medium-chain fatty acids cannot enter peroxisomes for very-long-chain oxidation
Correct answer: A. MCAD deficiency blocks beta-oxidation of C6-C12 fatty acids; acetyl-CoA generation is insufficient for ketogenesis
Explanation
MCAD oxidizes medium-chain (C6-C12) fatty acyl-CoA esters. Deficiency creates a block in the beta-oxidation spiral for medium-chain fatty acids, reducing the generation of acetyl-CoA that is essential for ketone body synthesis. During fasting or illness, glucose is depleted and the brain depends on ketones; without ketogenesis, hypoglycemia is profound and non-ketotic. The 'hypoketotic' feature is the diagnostic clue — normal fasting hypoketosis would show elevated ketones. Octanoylcarnitine accumulation in blood/urine is a diagnostic marker.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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