Methionine synthase (also known as 5-methyltetrahydrofolate-homocysteine methyltransferase) (MS, MeSe, MTR)

Methionine synthase is a crucial cobalamin-dependent enzyme that catalyzes the final step in regenerating methionine from homocysteine using a methyl group donated by N^5^-methyltetrahydrofolate (5-meTHF). This reaction also regenerates tetrahydrofolate (THF), linking folate metabolism with the methionine cycle essential for DNA synthesis and cellular growth. The enzyme contains four functional domains responsible for binding substrates including homocysteine, N^5^-methyltetrahydrofolate, cobalamin cofactor (vitamin B12), and S-Adenosylmethioninereactivation domain that interacts with reductases during catalytic cycles. Structurally, it undergoes significant conformational changes during catalysis allowing transfer of the methyl group via its bound vitamin B12 cofactor cycling between different oxidation states. It plays an indispensable role in maintaining proper cellular function through regulation of one-carbon units necessary for nucleotide biosynthesis and epigenetic regulation[1][2][3]. In humans, defects or deficiencies affecting this enzyme's activity can lead to elevated homocysteines levels associated with various pathologies including cardiovascular disease risk factors[1][3]. Its dependence on vitamin B12 makes it central to understanding certain nutritional deficiencies impacting health[2].

Other names

5-methyltetrahydrofolate S-homocysteine methyltransferaseMSMeSeMTR

Drugs targeting this enzyme would likely affect its catalytic mechanism involving: The transfer of a methyl group via cobalamin (vitamin B12) cofactor cycling between cob(I)alamin and methylcobalamin states. The enzymatic reaction involves nucleophilic attacks by sulfur of homocysteine on methylcobalamin forming methionine, followed by remethylation of cobalamin by N^5^-methyltetrahydrofolate.