Abstract

In isolated rat heart mitochondria incubated with excess ADP and malate, α-ketoisocaproate (KIC) at 0.05–0.1 mM more than doubled the rate of citrate cycle activity (measured as citrate accumulation in the presence of fluorocitrate). Replacement of fluorocitrate with arsenite increased pyruvate formation stoichiometrically with the previous increase in citrate formation. No enhancement of pyruvate or citrate accumulation was seen when malate was omitted or when KIC was replaced with equimolar leucine. KIC (leucine) did not give rise to acetyl CoA, nor was pyruvate formed by way of oxaloacetate and phosphoenolpyruvate. These findings suggest that KIC regulated the formation of pyruvate from malate by acting as a positive modulator of mitochondrial malic enzyme.

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