Regulatory Mechanisms in Carbohydrate Metabolism

Abstract 1. Aerobic lactic acid production in ascites tumor cells was not inhibited by rutamycin, indicating that the ADP and Pi required to sustain glycolysis were not supplied by mitochondrial ATPase. In contrast, the marked stimulation of lactic acid production induced by dinitrophenol was eliminated by rutamycin. 2. Parallel studies on the inhibition of lactic acid production and monovalent cation transport by ouabain revealed a close relationship between the two processes. About 1 mole of lactic acid was formed per mole of monovalent cation translocated. 3. The depression of glycolysis by ouabain was shown to result from the inhibition of (Na+, K+)-ATPase rather than from a lack of K+ as indicated by the high rate of aerobic glycolysis induced by dinitrophenol in the presence of ouabain. In the absence of dinitrophenol both Na+ and K+ were required for optimal glycolysis. 4. Evidence for a sodium-linked transport of Pi was obtained. 5. Dextran sulfate and other related compounds were found to have a profound effect on the permeability properties of ascites tumor cells. Glycolysis was markedly inhibited by dextran sulfate, and loss of intracellular ions, adenine nucleotides, and protein was demonstrated. In the presence of excess adenine nucleotides and Pi in the medium, dextran sulfate did not inhibit; in fact, it consistently stimulated glycolysis. It was shown that under these conditions AMP entered the cells and was converted into ATP. 6. The regulation of glycolysis in tumor cells by energy-linked ion transport is discussed.