A strict vegan presents with macrocytic anemia, subacute combined degeneration of the spinal cord, and elevated plasma methylmalonic acid. Serum B12 is 85 pg/mL. B12 serves as a cofactor for only two human enzymes. Which of the following correctly pairs these two enzymes with their cofactor form?

• A Methionine synthase uses adenosylcobalamin; methylmalonyl-CoA mutase uses methylcobalamin
• B Homocysteine methyltransferase uses hydroxocobalamin; propionyl-CoA carboxylase uses adenosylcobalamin
• C Methionine synthase (5-methyltetrahydrofolate-homocysteine methyltransferase) uses methylcobalamin; methylmalonyl-CoA mutase uses adenosylcobalamin ✓
• D Methionine synthase uses cyanocobalamin; methylmalonyl-CoA mutase uses hydroxocobalamin

Explanation

Two mammalian enzymes require B12: (1) cytoplasmic methionine synthase uses methylcobalamin (methyl-B12) to transfer a methyl group from 5-methylTHF to homocysteine, forming methionine and regenerating THF; (2) mitochondrial methylmalonyl-CoA mutase uses adenosylcobalamin (deoxyadenosyl-B12) to convert methylmalonyl-CoA to succinyl-CoA in odd-chain fatty acid/valine/isoleucine catabolism. B12 deficiency causes both elevated homocysteine (methionine synthase failure) and elevated methylmalonate (mutase failure), both of which are useful diagnostic markers.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.