Effect of atractyloside on glucose and pyruvate metabolism in rat diaphragm muscle

1. In the presence of 1.2mm-atractyloside oxygen uptake by rat diaphragm muscle incubated with 5.6mm-glucose decreases, as well as glycogen synthesis and carbon dioxide production. Lactate formation from glucose increases, but that of phosphoglycerate diminishes fivefold. 2. When pyruvate is used as substrate, atractyloside decreases oxygen uptake. 3. The specific radioactivity of the (14)CO(2) (mumoles of (14)CO(2)/mumole of oxygen), calculated at concentrations of [1-(14)C]pyruvate between 0.091mm and 91mm, lies between 3.1x10(-4) and 5.7x10(-1). Atractyloside increases the specific radioactivity of the (14)CO(2) with the lowest concentrations of substrate and has no effect when the substrate concentration is 91mm. 4. No appreciable effect of atractyloside on the anaerobic production of (14)CO(2) from [1-(14)C]pyruvate at various incubation times and various concentrations is found. 5. It is suggested that atractyloside induces anaerobic conditions in the tissue. Further, it produces a rise in the pyruvate concentration and an ATP deficiency in the cell. Consequently it stimulates pyruvate dismutation, and glycolysis, to which phosphorylation is linked at the substrate level.