Which enzymes require vitamin B12 as a cofactor?

• A. Pyruvate dehydrogenase and isocitrate dehydrogenase
• B. Glucokinase and hexokinase
• C. Methionine synthase and methylmalonyl-CoA mutase
• D. Succinate dehydrogenase and fumarase

Answer: (C)

Vitamin B12 serves as a cofactor for two key enzymes in human metabolism. One is methionine synthase, which transfers a methyl group from 5-methyl-tetrahydrofolate to homocysteine to form methionine, simultaneously regenerating tetrahydrofolate for one-carbon transfer reactions. The other is methylmalonyl-CoA mutase, which converts methylmalonyl-CoA to succinyl-CoA in the breakdown of odd-chain fatty acids and certain amino acids. These roles require cobalamin in different forms (methyl for methionine synthase and adenosyl for methylmalonyl-CoA mutase), so vitamin B12 deficiency impairs both methionine production and propionate metabolism.

Enzymes like pyruvate dehydrogenase rely on other cofactors (such as thiamine, lipoate, FAD, NAD+), not vitamin B12, and glucokinase/hexokinase are ATP-dependent kinases, while succinate dehydrogenase and fumarase depend on flavin/iron-sulfur clusters and other cofactors, not cobalamin.