Methionine synthase and other cobalamin-dependent enzymes (MTR/MUT)

Methionine synthase (MTR) and methylmalonyl-CoA mutase (MUT) are the two primary cobalamin-dependent enzymes in humans. Methionine synthase is a critical enzyme in the methionine cycle, catalyzing the conversion of homocysteine to methionine using methylcobalamin as a cofactor, which is essential for DNA synthesis and methylation (UniProt P13941). Methylmalonyl-CoA mutase uses adenosylcobalamin to convert methylmalonyl-CoA to succinyl-CoA, a key step in the catabolism of odd-chain fatty acids and certain amino acids (UniProt P22033). Deficiencies in these enzymes or their B12 cofactors lead to metabolic disorders such as hyperhomocysteinemia and methylmalonic acidemia, which can cause megaloblastic anemia and severe neurological damage (StatPearls NBK441923). Pharmacologically, methionine synthase is a target of nitrous oxide, which inactivates the enzyme by oxidizing its cobalt cofactor, potentially leading to myeloneuropathy (PubMed 3515511). Therapeutic intervention typically involves cobalamin supplementation to restore enzyme function in deficiency states.

Other names

5-methyltetrahydrofolate-homocysteine methyltransferaseMethylmalonyl-CoA mutaseVitamin B12-dependent enzymesCobalamin-dependent methyltransferaseMTRMUT

Nitrous oxide irreversibly inactivates methionine synthase by oxidizing the cobalt center of its cobalamin cofactor (PubMed 3515511). Cobalamin derivatives (Vitamin B12) act as essential cofactors: methylcobalamin facilitates methyl group transfer for methionine synthase, while adenosylcobalamin facilitates carbon skeleton rearrangement for methylmalonyl-CoA mutase (UniProt P13941, P22033).