Details of the methionine synthase reaction: Homocysteine reacts with the methyl group of methionine synthase-bound methyl-B12 to produce methionine and an unstable intermediate form of B12, cob(I)alamin. Cob(I)alamin then reacts with methyl-folate (CH3-THF) to generate free folate (THF) and regenerate methyl-B12. The vitamin shuttles between methyl-B12 and cob(I)alamin states. Cob(I)alamin is occasionally deactivated by oxidation to cob(II)alamin. Reductive remethylation of Cob(II)alamin requires a methyl group donated by S-adenosylmethionine. Deactivation usually occurs every few hundred cycles, but AD and age-related oxidative stress might augment this process .