Regulation of Pyruvate Metabolism in Rat‐Liver Mitochondria by K⁺ and Pi

The regulation of pyruvate metabolism in isolated rat‐liver mitochondria was studied in six media of varying ionic composition. In media containing low concentrations of P i (<10 mM), 12 to 62% of the pyruvate was metabolized to citrate and malate; in media having high P i concentrations (> 40 mM), pyruvate was metabolized exclusively to acetoacetate. Similarly, low K + concentrations (9 mM) stimulated formation of citrate and malate from pyruvate when the P i concentration was low but not when it was high. Inclusion of malate, as a source of oxaloacetate, in media which did not permit pyruvate alone to be metabolized to citrate and malate, eliminated accumulation of acetoacetate and caused pyruvate to be metabolized to citrate exclusively. Thus, it is possible that high P i concentrations or high K + concentrations inhibited pyruvate carboxylase but not citrate synthase. The dietary state (fasted or fed) of the rat prior to death affected the absolute or relative activities of these two path ways of pyruvate metabolism.