Vitamin B12 and methionine synthesis: a critical review. Is nature's most beautiful cofactor misunderstood?

The mechanism by which Vitamin B12 prevents demyelination of nerve tissue is still not known. The evidence indicates that the critical site of B12 function in nerve tissue is in the enzyme, methionine synthase, in a system which requires S-adenosylmethionine. In recent years it has been recognized that S-adenosylmethionine gives rise to the deoxyadenosyl radical which catalyzes many reactions including the rearrangement of lysine to beta-lysine. Evidence is reviewed which suggests that there is an analogy between the two systems and that S-adenosyl methionine may catalyze a rearrangement of homocysteine on methionine synthase giving rise to iso- or beta-methionine. The rearranged product is readily degraded to CH3-SH, providing a mechanism for removing toxic homocysteine.