A 4-year-old boy with developmental delay and metabolic acidosis has elevated urine methylmalonic acid. Dietary history reveals heavy reliance on dairy and meat. His odd-chain fatty acid intake generates a three-carbon intermediate during beta-oxidation that enters the TCA cycle as succinyl-CoA. Which cofactor is required for the final intramolecular rearrangement of this pathway?

• A Vitamin B12 (cobalamin) ✓
• B Thiamine pyrophosphate
• C Biotin
• D Folic acid

Explanation

Odd-chain fatty acids yield propionyl-CoA in the final thiolytic cleavage. Propionyl-CoA is carboxylated by propionyl-CoA carboxylase (biotin-dependent) to D-methylmalonyl-CoA, racemized, then converted to succinyl-CoA by methylmalonyl-CoA mutase, an adenosylcobalamin (vitamin A12)-dependent enzyme. A12 deficiency causes methylmalonic aciduria. Biotin acts earlier at the carboxylation step, not the mutase step, which kills option C.

Reference: Lippincott's Illustrated Reviews: Biochemistry, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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