THE EFFECT OF FLUOROACETATE ON ENZYMES AND ON TISSUE METABOLISM. ITS USE FOR THE STUDY OF THE OXIDATIVE PATHWAY OF PYRUVATE METABOLISM

Among the organic halogen compounds, those containing fluorine occupy a unique position regarding their chemical and physiological properties. Because of the large heat of formation of the C-F bond (114 kilocalories (l)), the addition of fluorine to the carbon atom brings forth, in most cases, a greater stability, especially among aliphatic compounds. This chemical stability is usually accompanied by lack of physiological action. Fluoroacetate is a striking exception to the physiologic inertia of fluorine aliphatic compounds; long ago it was found toxic to certain invertebrates, it was patented in 1927 (2) as a preservative against moths, and is now used as a rodent&de (3). This high toxicity of fluoroacetate compared with the nontoxicity of other organic aliphatic fluorine compounds is indeed of greater interest because the chemical stability is still maintained. We present in this paper some of the results of work done in 1944 on the mechanism of action of fluoroacetate on enzymes and on the metabolism of animal tissues. The chemical stability of the fluorine of fluoroacetate and the lack of inhibition of the activity of isolated enzymes were in striking contrast to its powerful inhibition of acetate oxidation in animal tissues. Advantage has been taken of this inhibition to study the oxidative pathway of pyruvate metabolism.