The Relation of Thiamine to Citric Acid Metabolism*

The discovery of the identity of thiamine pyrophosphate and cocarboxylase and the recognition of the ester as the predominant form of thiamine in yeast (1, 2) and animal tissues (3, 4) has been followed by several papers which have clearly demonstrated that cocarboxylase is essential for the oxidative metabolism of pyruvic acid (5-7). However, it has become clear that pyruvic acid is one of the most reactive intermediates in carbohydrate metabolism and that the end-products of its oxidation may vary with different organisms or tissues and with the internal conditions of the cell (6). Thus, it has been demonstrated in vitro that the oxidation of pyruvic acid under various conditions may yield acetic acid (6, 8, 9), acetic and formic acids (6), lactic and acetic acids (9, lo), acetoacetic and P-hydroxybutyric acids (II), succinic acid (9, 12), and citric acid (13, 14). Lipmann (5) and Barron and Lyman (6) have demonstrated with bacteria that cocarboxylase is essential for the aerobic oxidation of pyruvic acid to acetic acid, and for the anaerobic dismutation to acetic and lactic acids. Banga, Ochoa, and Peters (7) have demonstrated that thiamine pyrophosphate is essential for the oxidation of pyruvate by brain. While the over-all effect of cocarboxylase upon the oxidation of pyruvic acid is beyond question, its function in the specific oxidative transformations is not yet clear. In the absence of thiamine, it appeared likely that some of these reactions might be significantly affected.