The Role of Vitamin B12 in Methionine Biosynthesis in Avian Liver.

A consideration of numerous studies in viva indicates that the metabolism of methionine, folic acid, and cyano-B1$ is interrelated. The vitamin has a sparing effect on the methyl group requirement of young chickens, and, conversely, methionine has a sparing effect on the cyano-Blz requirement in chickens and rats (l-4). A more direct demonstration of an impairment in methyl group biosynthesis de novo was the inability of cyano-B12deficient rats and pigs to convert 3-14C-serine and 2-14C-glycine to the trimethylamine moiety of choline (5, 6). This effect was not upon transmethylation (7). The formimino group of formininoglutamic acid, a catabolic product of histidine, is normally transferred to folate-H4 so that little, if any, excretion of FGA occurs in response to a histidine load. As a consequence of cyano-Blz deficiency in rats and chickens, an increased FGA excretion occurs which is diminished by an increased dietary intake of methionine (8, 9). Elevated FGA excretions in response to histidine loads have also been reported in patients with pernicious anemia and megaloblastic anemia of pregnancy (10, 11). The elucidation of methionine biosynthesis in Escherichia coli mutants has indicated a site at which the methionine, folic acid, and cyano-Blz interrelationship may occur. The methyl transfer from methylfolate-H4 to homocysteine (12), the terminal step of the biosynthetic pathway, is one of the known metabolic reactions which requires a cobamide prosthetic group (13-16). Other cofactors required for this reaction are reduced flavin (15) and Sadenosylmethionine (17, 18). Guest et al. (19) demonstrated that methyl-BIz could replace the cyano-BIp requirement in the enzyme system obtained from methionine-cyano-Blz auxotrophs of E. coli W, and, of more significance, the methyl group of methyl-B12 was transferred enzymatically to homocysteine to form methionine. The active form of the vitamin in the methylfolate-H4-transferase2 reaction is as yet unknown, but recent