Biochemistry of fluoroacetate poisoning. Isolation of an active tricarboxylic acid fraction from poisoned kidney homogenates

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Abstract
The hypothesis that fluoroacetate after activation condenses with oxalo-acetate to form a fluorotricarboxylic acid which then jams the tricarboxylic acid cycle was tested by incubating homogenates of guinea pig and ox kidney cortex with fumarate, fluoroacetate and adenosine triphosphoric acid. The citric acid so formed was isolated by selective precipitations with Ba and Pb at different pH values. The final fractions contained citric and other tricarboxylic acids, some phosphoric acid and occasionally di-carboxylic acids; the phosphoric acid could be largely separated by precipitation with ethanol-water mixture. These fractions synthesized enzymically showed in vitro properties similar, though different in detail, to those of fluoroacetate, in the sense that they inhibited the disappearance of citrate when added to a reinforced guinea pig kidney homogenate in the presence of either citrate or fumarate. The [image]active[image] fractions were inseparable chromatographically from the tricarboxylic acids; they contained small amts. of combined fluorine and were free from fluoroacetic acid. In terms of fluorine content, they were more active than fluoroacetate in preventing the disappearance of citrate. All the evidence obtained was consistent with the conclusion that the activity of the fractions was due to the presence in them of a fluorotricarboxylic acid as postulated in the hypothesis.