The effect of cobalamin on the quantitative utilization of serine, glycine and formate for the synthesis of choline and methyl groups of methionine

Abstract

The conversion of the beta-C atom of serine, the alpha-C atom of glycine and the C atom of formate into the methyl groups of choline and methionine was studied quantitatively by feeding completely defined diets containing these precursors, labeled with C14, to young rats over prolonged periods. In all expts. the radioactivity of the methionine methyl groups exceeded that of the choline methyl groups suggesting that most of the newly synthesized methyl groups are first incorporated into methionine and then transferred to choline by transmethylation. With diets devoid of preformed methyl groups, but containing [beta-C14] serine and cobalamin, the methyl group of the visceral methionine had 70% of the radioactivity of the beta-C of serine isolated from the same source. This indicates that the hydroxymethyl group of serine is quantitatively the most important precursor of synthesized methyl groups. In similar expts. with [alpha-C14] glycine, the alpha-C atom of glycine was relatively inefficient as a precursor of methyl groups. Formate was an efficient precursor of methyl groups, but its conversion to the hydroxymethyl group of serine was relatively poor. Results indicate that formation is extensively converted to a substance which is an intermediate in the synthesis of methyl groups from serine. Cobalamin increased the conversion of all 3 precursors into the methyl groups of methionine and into both the methyl groups and the ethanolamine moiety of choline. The stimulating effect of cobalamin on methyl-group synthesis reduced, in paired-feeding expts. With diets containing 2% [alpha-C14] glycine, cobalamin increased the relative incorporation of isotope into the methyl groups of choline, compared with that into the ethanolamine moiety.