The effect of vitamin B12 on the metabolism of formate and certain formate precursors by the rat.

The ability of vitamin B12 (cobalamin) to spare the dietary requirement of animals for labile methyl donors, such as choline or methionine, is now well established (for a review see Arnstein, 1958a). This effect appears to be due to stimulation of synthesis of methyl groups, as shown by an increased utilization of a variety of 14C-labelled precursors, including formate (Arnstein & Neuberger, 1953), methanol (Verly & Cathey, 1955), the a-carbon atom of glycine (Stekol, Weiss & Weiss, 1952; Arnstein & Neuberger, 1953) and the p-carbon atom of serine (Arnstein & Neuberger, 1953). It has also been known for some time that certain micro-organisms, notably Eacheriohia coli, require vitamin B12 for the biosynthesis of the methyl group of methionine (Davis & Mingioli, 1950), and considerable progress has been made towards elucidating the biochemical function of the vitamin in this reaction (Guest, 1959; Woods, 1958). There is some doubt, however, to what extent this function of vitamin B12 in the biosynthesis of labile methyl groups can account for its physiological importance, particularly in animal metabolism where methionine is an essential amino acid which can only reduce the requirement for vitamin B12 but not replace it completely. In order to investigate this problem and the specificity of the action of vitamin B12 on biosynthesis of methyl groups, a comparison has now been made of the effect of vitamin B12 on the conversion of formate and two formate precursors, serine and histidine, into methyl groups and on the metabolism of formate and histidine into other products such as serine. Some ofthe results ofthis work have been published in a preliminary note (Arnstein, 1958b).