The synthesis of choline and creatine in rats under various dietary conditions.

The deficiency of folic acid in the rat produced a reduction in the utilization of either the a-carbon of glycine or the P-carbon of serine for the synthesis of both moieties of choline. On the other hand, the deficiency in vitamin Blz reduced the incorporation of only the a-carbon of glycine; the utilization of the P-carbon of serine was not affected (1). From these data we concluded that vitamin B1% (or its physiological derivative) was concerned in some unknown way in the conversion of glycine to serine (1). Similar results were reported by others (2). The manner in which these carbon atoms of glycine and serine are transformed into the methyl groups of choline is not known, but it is presumed to be indirect. The carbon fragments of glycine and serine are presumed to be converted to the methyl group of some intermediate metabolite, which then, by the process of transmethylation, transfers its methyl group to an appropriat,e acceptor to yield choline, creatine, etc. These carbon fragments of glycine and serine are not necessarily identical, nor are they released from the amino acids via the same metabolic routes (3, 4, 1). One of the intermediates in the conversion of these single carbon fragments to the methyl group of choline and creatine is presumed to be met’hionine (5). That the carbon of formate, on its way to the methyl group of methionine, does not enter the choline molecule has been demonstrated in experiments in vitro (6). In the experiments presented here we investigated the extent of the incorporation of the carbon of the methyl groups, of methionine, betaine, and choline into tissue choline and creatine in the folic acid-deficient or the vitamin Blz-deficient rat. The extent of the incorporation of the methyl group of methionine or of the p-carbon of serine into choline and creatine was also investigated in the pyridoxine-deficient rat. There was a possibility that the extent of the transfer of the methyl group of methionine to choline or creatine was a function not only of adequate operation of the systems involved in the transmethylations to choline and creatine, but also