5-methyltetrahydrofolate--homocysteine methyltransferase (MTR)

5-methyltetrahydrofolate--homocysteine methyltransferase, commonly known as methionine synthase (MTR), is a critical enzyme in the one-carbon metabolism pathway that catalyzes the transfer of a methyl group from 5-methyltetrahydrofolate to homocysteine, resulting in the formation of methionine and tetrahydrofolate [UniProt: Q99707]. This enzyme requires vitamin B12 in the form of methylcobalamin as an essential cofactor for its catalytic activity [PubMed: 11504545]. By linking the folate cycle and the methionine cycle, MTR plays a pivotal role in maintaining cellular levels of S-adenosylmethionine (SAM), which is the primary methyl donor for DNA and protein methylation [PubMed: 15135909]. Genetic mutations in the MTR gene or nutritional deficiencies in its cofactors can lead to severe metabolic disorders like homocystinuria and megaloblastic anemia [NIH: Genetic and Rare Diseases Information Center]. Dysfunction of this enzyme is also associated with an increased risk of cardiovascular disease and neural tube defects due to the accumulation of homocysteine. Pharmacologically, the enzyme is most notably recognized for its extreme sensitivity to nitrous oxide, which irreversibly inactivates the enzyme by oxidizing its cobalamin cofactor, potentially leading to acute neurotoxicity or hematological complications [PubMed: 12559332]. Conversely, cobalamin-based therapies aim to restore MTR function in patients with metabolic deficiencies [PubChem: CID 5460491].

Other names

Methionine synthaseVitamin B12-dependent methionine synthaseMSMeSeTetrahydrofolate-methyltransferase5-methyltetrahydrofolate-homocysteine S-methyltransferaseCobalamin-dependent methionine synthase

Irreversible inactivation of the cob(I)alamin cofactor via oxidation by nitrous oxide; cofactor replacement or supplementation with cobalamin derivatives to restore and maintain enzyme activity.