Pyruvate oxidation in rat and human skeletal muscle mitochondria

Abstract

Pyruvate oxidation in rat and human skeletal muscle mitochondria was studied by measuring the rate of 14CO 2 production from [1- 14C]pyruvate in the presence of 1 m m pyruvate, an excess of ADP, and varying amounts of citric acid cycle intermediates or carnitine. The rate of pyruvate oxidation is controlled by the availability of acetyl-CoA acceptor since addition of citric acid cycle intermediates or carnitine results in a stimulation of pyruvate oxidation. Pyruvate oxidation proceeds at its maximal rate in the presence of malate since no further stimulation is observed by addition of carnitine. It is concluded that pyruvate dehydrogenase is the rate-limiting step during pyruvate oxidation in the presence of malate. In human skeletal muscle mitochondria pyruvate oxidation proceeds maximally both in the presence of malate or carnitine. Parallel incubations of these mitochondria with [1- 14C]pyruvate plus malate and [1- 14C] pyruvate plus carnitine may allow one to establish disturbances in pyruvate oxidation and to discriminate between defects in the pyruvate dehydrogenase complex and in the activity of the citric acid cycle.