A study of formate utilization in pigeon liver extract.

It is generally recognized that formate is converted to a compound which is utilized in the synthesis of serine (l-3), purines (4, 5), and labile methyl groups (6-8) in animal tissues. Futhermore, compounds which, in the course of their metabolism, form a lrCl compound”l similar to the one formed from formate likewise serve as precursors in the synthetic reactions mentioned above (cf. (9, 10)). Little is known, however, about t]he nature of this l-carbon precursor or of the mechanism of its formation and utilization. In an earlier communication (8) it was demonstrated that, methionine can be formed by a pathway independent of transmethylation from choline or betaine. This has been postulated as a direct de novo synthesis of methionine from homocysteine and a “l-carbon compound” formed from formate. Although the existence of ahernative pathways for the incorporation of formate-Cl4 into labile methyl groups cannot be excluded, the direct formation of a new labile methyl group in methionine does provide a mechanism for the eventual distribution of the formate carbon into all the methyl groups derived from methionine. Furthermore, the de novo synthesis of methionine by this mechanism supports the concept (11) that a net synthesis of labile methyl groups can occur in the absence of a nutritional supply of these groups. In the present investigation the mechanism of methionine synthesis from