The metabolism of choline and its conversion to glycine in the rat.

and that it is betaine which serves as the immediate donor of methyl groups in transmethylation reactions. In view of an earlier finding that betaine was readily demethylated to glycine in the rat (4), it was considered of interest to compare injected isotopic choline and betaine as precursors of the glycine moiety of hippuric acid in the intact animal. The present finding that betaine and choline were indeed efficient precursors of glycine led to the inclusion of dimethylethanolamine among the compounds studied, in view of the fact that du Vigneaud et cal. (5) had suggested that this compound might be “the principal demethylation product of choline” in the rat. The technique employed was based on that of Shemin (6) who had compared a variety of substances with respect to their capacities to yield glycine under these circumstances. An alternative fate of choline is suggested by the findings of de la Huerga and Popper (7) who recovered as much as two-thirds of the choline nitrogen, fed to patients with hepatobiliary disease, as urinary trimethylamine and trimethylamine oxide. A 2-carbon residue might well arise from this reaction. Alternatively glyoxylic acid might arise from the glycine oxidasecatalyzed oxidation of sarcosine (8) derived in turn from the partial demethylation of betaine. Reamination of such a 2-carbon fragment might regenerate glycine, and indeed glyoxylic acid has been observed to serve as a precursor of glycine carbon in the rat (9). Choline labeled with Cl4 in the ethanolic residue as well as with N15 has been therefore employed. Glycine arising from such choline by the latter mechanisms would exhibit greater dilution with respect to N15 than to U4, whereas in glycine formed via demethylation of betaine, both isotopes would be equally diluted. One of the reported effects of aminopterin poisoning is an inhibition of choline oxidase act)ivity. This has been demonstrated in a variety of tissue