Inhibition of glycolysis in rat skeletal muscle by malonate

Abstract

A rat-muscle suspension from powdered frozen muscle is described. Malonate at concentrations above 0.06M inhibits lactate formation almost completely and causes accumulation of 3-phosphoglycerate, glycerol 1-phosphate and phosphoenol-pyruvate. Addition of phosphoenolpyruvate to the malonate-treated suspension gives rise to 3-phosphoglycerate but not to pyruvate and lactate, as in the untreated suspension. The inhibition of pyruvate kinase results in a reversal of the glycolytic reactions which cannot proceed beyond 3-phosphoglycerate owing to lack of ATP. Addition of pyruvate to the malonate-blocked system results in a stoicheiometric formation of lactate. 3-Phosphoglycerate production is increased, but no glycerol 1-phosphate is formed. Malonate at a concentration of 0.03M only partly inhibits glycolysis in our system. Experiments on the pure enzyme system also showed that, though 0.06M-malonate strongly inhibits pyruvate kinase, 0.03M-malonate is only partially effective. These results are discussed in the light of previous experiments on dog heart-lung preparations in which 0.03M-malonate did not interfere with heart action but 0.06M malonate caused marked failure, in spite of the fact that the extent of succinate accumulation with both concentrations was the same.