Vitamin B_{12} and methionine synthesis: A critical review. Is nature's most beautiful cofactor misunderstood?

Article type: Research Article

Authors: Toohey, John I.

Affiliations: Cytoregulation Research, Elgin, Ontario, Canada KOG 1EO. E-mail: cytoreg@hotmail.com

Abstract: The mechanism by which Vitamin B_{12} prevents demyelination of nerve tissue is still not known. The evidence indicates that the critical site of B_{12} 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 CH_3-SH, providing a mechanism for removing toxic homocysteine.

Keywords: 5'-Deoxyadenosyl radical, hyperhomocysteinemia, methionine synthesis, methionine transamination, cobalamins, polyamines, methylthio growth factor

Journal: BioFactors, vol. 26, no. 1, pp. 45-57, 2006