Biochemistry · Lipid Metabolism (Fatty Acid Synthesis and Oxidation, Lipoproteins, Cholesterol)

A patient with untreated vitamin B12 deficiency eats a meal rich in odd-chain fatty acids. A metabolite accumulates upstream of the block. Which cofactor pair normally converts propionyl-CoA to succinyl-CoA?

  • A Biotin then cobalamin (methylmalonyl-CoA mutase)
  • B Thiamine pyrophosphate then lipoamide
  • C FAD then FMN
  • D Pyridoxal phosphate then tetrahydrobiopterin
Correct answer: A. Biotin then cobalamin (methylmalonyl-CoA mutase)

Explanation

Odd-chain fatty acid oxidation yields propionyl-CoA, which is carboxylated by biotin-dependent propionyl-CoA carboxylase to D-methylmalonyl-CoA, racemized, then rearranged by the B12-dependent methylmalonyl-CoA mutase to succinyl-CoA, an anaplerotic TCA intermediate. In B12 deficiency, methylmalonyl-CoA and methylmalonic acid accumulate, distinguishing it from folate deficiency where MMA remains normal. TPP and lipoamide belong to oxidative decarboxylation reactions, not this pathway.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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