5-methyltetrahydrofolate-homocysteine methyltransferase (MTR)

5-methyltetrahydrofolate-homocysteine methyltransferase, commonly known as methionine synthase, is a critical enzyme that catalyzes the remethylation of homocysteine to methionine using methylcobalamin (a derivative of vitamin B12) as a cofactor and 5-methyltetrahydrofolate as a methyl donor. This reaction stands at the intersection of the folate and methionine cycles, playing a dual role in supporting DNA synthesis through the regeneration of tetrahydrofolate and facilitating cellular methylation reactions via the production of S-adenosylmethionine (SAMe). SAMe is essential for the methylation of myelin basic protein, which is necessary for the structural integrity of the central and peripheral nervous systems. Clinically, a deficiency in this enzyme or its B12 cofactor leads to the 'folate trap,' resulting in megaloblastic anemia due to impaired erythropoiesis and hyperhomocysteinemia, a known risk factor for cardiovascular disease. Furthermore, the loss of methionine synthase activity is linked to subacute combined degeneration of the spinal cord, characterized by the demyelination of dorsal and lateral columns. Pharmacologically, the enzyme is the primary target of vitamin B12 supplementation therapies and is notably inactivated by nitrous oxide, which oxidizes the cobalt center of the B12 cofactor, potentially leading to acute neurological symptoms in patients with marginal B12 stores.

Other names

Methionine synthaseMSVitamin B12-dependent methionine synthaseMeTHF-homocysteine S-methyltransferase

Cofactor supplementation (vitamin B12 forms) to restore enzymatic activity; Irreversible oxidation of the cobalamin cofactor (Nitrous oxide) leading to enzyme inhibition.