An infant born to a mother with poorly controlled phenylketonuria has microcephaly and congenital heart disease. Separately, an adult patient with severe vitamin B12 deficiency has elevated serum methylmalonic acid with normal homocysteine excluded. Which product of odd-chain fatty acid oxidation accounts for the elevated methylmalonic acid?

• A Acetoacetyl-CoA
• B Hydroxymethylglutaryl-CoA
• C Malonyl-CoA
• D Succinyl-CoA formed from propionyl-CoA ✓

Explanation

Odd-chain fatty acids yield one propionyl-CoA per molecule at the final spiral. Propionyl-CoA is carboxylated to methylmalonyl-CoA by propionyl-CoA carboxylase (biotin), then rearranged to succinyl-CoA by methylmalonyl-CoA mutase, which needs adenosylcobalamin. In D12 deficiency this step stalls and methylmalonate accumulates. Even-chain fatty acids yield only acetyl-CoA, never propionate, which kills distractor A.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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