Formate Metabolism by Animal Tissues*?

Many studies on the metabolism of formic acid by a variety of animal tissues have shown that an appreciable portion of this substrate is oxidized to carbon dioxide (6-13). Since the initial observation of Battelli (6) and Battelli and Stern (7) on the oxidation in vitro of formate, various uncorrelated attempts have been made to identify the responsible enzymes to explain the mechanism of this reaction. Battelli and Stern (7) first established that the oxidation of formate by animal tissues in presence of Hz02 was an enzymecat.alyzed reaction. Plaut et al. (14) were the first to demonstrate that injected formate-Cl4 was oxidized to Cl402 and that a major portion of the formate was incorporated into serine. These results led Plaut et al. to postulate that formate oxidation occurred by incorporation into serine, followed by oxidation of serine to pyruvate, and finally the degradation of pyruvate to COz. Later Plaut and Lardy (15) and Kruhoffer (16) demonstrated the direct oxidation of formate to CO2 without the intermediate formation of serine. Mathews and Vennesland (17) demonstrated that in pea extracts a DPN-formic dehydrogenase was responsible for the oxidation, and AMP did not influence this oxidation. However, supernatants from rat liver and kidney oxidized formic acid in presence of either AMP, ATP, or ATP and DPN, respectively, thus differing from the pea extracts. Nakada and Weinhouse (18) presented evidence that in animal tissues the peroxidative activity of catalase, in the form of a catalase peroxide complex, is responsible for the oxidation of formic acid. In 1955, Weinhouse (19) described a model system with the use of xanthine oxidase and catalase to indicate that hypoxanthine oxidation by xanthine oxidase furnishes hydrogen peroxide which, in combination with catalase, oxidized formate. He summarized the findings from his laboratory as follows: “We believe this may be a coupled oxidation phenomenon.” During the studies on the metabolism of formate by animal tissues (20), it was desirable to find the exact mechanism of formate oxidation, hence the present investigations were undertaken. These studies establish that in the rat liver extracts cntalase forms a complex with hydrogen peroxide derived from other enzymic systems, and it is this complex which is responsible for the oxidation of formic acid to carbon dioxide.