Methionine synthase (MTR) (MTR)

Methionine synthase (MTR) is a critical enzyme in the one-carbon metabolism pathway, responsible for the remethylation of homocysteine to methionine [1, 4]. This process requires 5-methyltetrahydrofolate as a methyl donor and methylcobalamin, a derivative of vitamin B12, as an essential cofactor [2]. By converting homocysteine to methionine, the enzyme facilitates the production of S-adenosylmethionine (SAM), which is the universal methyl donor for DNA, proteins, and lipids [1]. It also regenerates tetrahydrofolate, which is necessary for nucleotide synthesis and cell division [4]. Dysfunction of methionine synthase, whether due to genetic mutations or nutritional deficiencies, leads to elevated homocysteine levels and impaired DNA synthesis, manifesting as megaloblastic anemia [2]. The enzyme is a significant pharmacological target for nitrous oxide, an anesthetic that irreversibly inactivates the cobalamin cofactor through oxidation [3]. Chronic or acute inhibition by nitrous oxide can lead to subacute combined degeneration of the spinal cord due to impaired methylation in the central nervous system [3]. Therapeutic management often involves supplementation with vitamin B12 and folic acid to ensure adequate enzyme activity and prevent cardiovascular or neurological complications [2, 4].

Other names

5-methyltetrahydrofolate-homocysteine methyltransferaseVitamin B12-dependent methionine synthaseMSMTRHomocysteine methyltransferase

Irreversible inhibition via oxidation of the cobalamin cofactor (Nitrous oxide); Enzymatic cofactor/substrate replacement (Cobalamin/Folate) [2, 3, 4].