Studies on Biological Oxidations

Pyruvic acid is one of the most reactive substances among those of importance in cellular metabolism. When carbohydrate is split during fermentation, pyruvic acid is the main end-product of the resulting series of phosphorylated oxidation-reductions. It thus becomes the immediate source for the formation of both lactic acid and alcohol. Pyruvic acid is decarboxylated by yeast; it may react with other ketonic acids in a Cannizzaro type reaction (dismutation) (Krebs (1)); it may likewise react with amino acids with intermolecular transfer of amino groups (Braunshtem and Kritsman (2)), the orientation of pyruvic acid metabolism being determined by a variety of different factors. The oxidation of pyruvic acid by gonococci was studied in 1932 by Barron and Miller (3) who postulated the existence of an enzyme, a-ketonoxidase, able to catalyze the oxidation of ar-ketonic acids. Other properties of this enzyme were later studied by Barron (4). To distinguish it from a-hydroxyoxidase, the enzyme concerned with the oxidation of lactic acid, a number of inhibitors were found having opposite effects on the two enzymes. Krebs and his coworkers (5, 6) challenged this interpretation and postulated that the oxidation of cll-ketonic acids is not brought about by molecular oxygen, but by a dismutation. In this paper an endeavor is made to show that pyruvic acid in the presence of oxygen is oxidized directly; that the dismutation of pyruvic acid observed by a number of authors and confirmed by Krebs and his coworkers is a process independent of the oxidation process. Furthermore, Lipmann’s studies (7) on the action