During fatty acid oxidation, propionyl-CoA is generated from odd-chain fatty acids. The conversion of propionyl-CoA to succinyl-CoA requires two enzymatic steps. The second step (methylmalonyl-CoA mutase) requires which cofactor?

• A Biotin (as a carboxyl carrier in the first step, catalysed by propionyl-CoA carboxylase)
• B Thiamine pyrophosphate, as an acyl carrier in the rearrangement reaction
• C Adenosylcobalamin (vitamin B12 coenzyme form), which is required for methylmalonyl-CoA mutase to isomerise methylmalonyl-CoA to succinyl-CoA ✓
• D Pyridoxal phosphate (PLP) for the transamination step needed to prepare the substrate

Explanation

Propionyl-CoA → methylmalonyl-CoA (Step 1: propionyl-CoA carboxylase, requires biotin and ATP). Methylmalonyl-CoA → succinyl-CoA (Step 2: methylmalonyl-CoA mutase, requires adenosylcobalamin, the 5'-deoxyadenosylcobalamin form of vitamin B12). In B12 deficiency, methylmalonyl-CoA accumulates, and methylmalonic acid is elevated in urine — a specific diagnostic marker of cobalamin deficiency. Succinyl-CoA then enters the TCA cycle. This explains why B12 deficiency causes neurological damage (odd-chain fatty acid beta-oxidation in myelin is impaired).

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.