FORMATION OF FORMALDEHYDE AND FORMATE IN THE BIOOXIDATION OF THE METHYL GROUP

Abstract

When the oxidation of the "biologically labile" methyl group to carbon dioxide was first reported several years ago, it was pointed out that the identity of the intermediates produced in this reaction and their roles in metabolic processes were matters of considerable interest (1).It seemed probable that these intermediates included single carbon compounds whose normal occurrence and function in .higheranimals had received comparatively little attention.As an initial approach to this problem, the assumption was made that formaldehyde and formic acid are among the compounds produced in the oxidation of methyl groups found in the body attached to S and N, and experiments were conducted to test the validity of this hypothesis.In exploratory investigations, it was found that the methyl groups of Ci4-labeled methionine, betaine, choline, and .sarcosinewere oxidized to Cl402 by rat liver slices.However, only the methyl group of sarcosine was oxidized to carbon dioxide when liver homogenates were employed.Since homogenates offer advantages over tissue slices with respect to the isolation of metabolic products, sarcosine was used as the source of methyl groups in the subsequent isolation experiments.'Evidence of the demethylation of sarcosine to glycine in vivo was reported by Abbot and Lewis (3) in 1939.Shortly thereafter, Bloch and Schoenheimer (4) fed N16-labeled sarcosine to rats and showed by isolation experiments that it was rapidly and directly demethylated to form glycine without deamination.In 1941, Handler, Bernheim, and Klein *A research grant from the Lederle Laboratories Division of the American Cyanamid Company has made the present investigation possible.1 Although ssrcosine was prepared in 1847 by Liebig (2) as a degradation product of creatine, no reference could be found in the literature to its occurrence in higher animals.Experiments were therefore undertaken to obtain evidence for the production of sarcosine in the animal body.The experiments have shown that sarcosine is formed in the rat and that the methyl groups of methionine and betaine contribute to its formation (Horner, W. H., and Mackenzie, C. G., J. Biol.Chem., in press).These results indicate that sarcosine may be used to study intermediates formed in the oxidation of methyl groups provided by "biologically labile" methyl compounds.