Biochemical stability of the methyl group of creatine and creatinine.

Recent investigations in this laboratory (l-3) have shown that appreciable quantities of the methyl group ingested in the form of methionine are oxidized to carbon dioxide. Inasmuch as the methyl groups of methionine, choline, and betaine are directly or indirectly interchangeable in the animal body, it is evident that the methyl groups supplied by choline and betaine, indeed by all “biologically labile” methyl compounds, can likewise be degraded to carbon dioxide and water. However, the experiments with methionine provide no information concerning the oxidation of the methyl group of creatine, since the methyl group of creatine does not participate in transmethylation reactions (4). A direct test of the susceptibility of this methyl group to oxidation was therefore desirable. Creatine and creatinine containing Cl4 in the methyl group were synthesized and administered to rats in doses of 1.1 to 1.4 gm. per kilo of body weight. The expired carbon dioxide was collected and examined for the presence of radioactivity. The amount of Cl4 excreted in the urine and feces wm also determined.