Key enzyme in methionine and folate homeostasis responsible for the reactivation of methionine synthase (MTR/MS) activity by catalyzing the reductive methylation of MTR-bound cob(II)alamin (PubMed:17892308). Cobalamin (vitamin B12) forms a complex with MTR to serve as an intermediary in methyl transfer reactions that cycles between MTR-bound methylcob(III)alamin and MTR bound-cob(I)alamin forms, and occasional oxidative escape of the cob(I)alamin intermediate during the catalytic cycle leads to the inactive cob(II)alamin species (Probable). The processing of cobalamin in the cytosol occurs in a multiprotein complex composed of at least MMACHC, MMADHC, MTRR and MTR which may contribute to shuttle safely and efficiently cobalamin towards MTR in order to produce methionine (PubMed:27771510). Also necessary for the utilization of methyl groups from the folate cycle, thereby affecting transgenerational epigenetic inheritance (By similarity). Also acts as a molecular chaperone for methionine synthase by stabilizing apoMTR and incorporating methylcob(III)alamin into apoMTR to form the holoenzyme (PubMed:16769880). Also serves as an aquacob(III)alamin reductase by reducing aquacob(III)alamin to cob(II)alamin; this reduction leads to stimulation of the conversion of apoMTR and aquacob(III)alamin to MTR holoenzyme (PubMed:16769880). H(+) + 2 methylcob(III)alamin-[methionine synthase] + NADP(+) + 2 S-adenosyl-L-homocysteine = 2 cob(II)alamin-[methionine synthase] + NADPH + 2 S-adenosyl-L-methionine A + 2 cob(II)alamin + 2 H(+) + 2 H2O = AH2 + 2 aquacob(III)alamin kcat is 3.92 sec(-1) for the reduction of cytochrome c3 with NADPH (PubMed:17892308). kcat is 0.24 sec(-1) for the reduction of cytochrome c3 with NADH (PubMed:17892308). kcat is 220 min(-1) for aquacob(III)alamin reduction (PubMed:16769880). Forms a multiprotein complex with MMACHC, MMADHC AND MTR. Found in all tissues tested, particularly abundant in skeletal muscle. The disease is caused by variants affecting the gene represented in this entry. Disease susceptibility is associated with variants affecting the gene represented in this entry. It is debated whether the reduction of free aquacob(II)alamin occurs spontaneously or is enzyme catalyzed. The hidden things - Issue 166 of December 2014