Contains zinc and cobamide. The enzyme becomes inactivated occasionally during its cycle by oxidation of Co(I) to Co(II). Reactivation by reductive methylation is catalysed by the enzyme itself, with S-adenosyl-L-methionine as the methyl donor and a reducing system. For the mammalian enzyme, the reducing system involves NADPH and EC
1.16.1.8, [methionine synthase] reductase. In bacteria, the reducing agent is flavodoxin, and no further catalyst is needed (the flavodoxin is kept in the reduced state by NADPH and EC
1.18.1.2, ferredoxin---NADP+ reductase). Acts on the monoglutamate as well as the triglutamate folate, in contrast with EC
2.1.1.14, 5-methyltetrahydropteroyltriglutamate---homocysteine S-methyltransferase, which acts only on the triglutamate.