Restoration of glycolysis and respiration in Ehrlich ascites tumor cells inhibited by 2,2'-dithiodipyridine

Abstract

Glycolysis and respiration of Ehrlich ascites cells are strongly inhibited by 2,2'-dithiodipyridine (2-PDS). If such inhibited cells are treated with dithiothreitol (DTT) + NADP + + ATP, with glucose as substrate, the anaerobic production of CO 2 is restored to an extent about 50 per cent that of untreated cells, and lactate production to an extent of 30 per cent. The excess CO 2 over lactate production is due to hydrolysis of the exogenous ATP, presumably by action of ATPase. DTT alone causes a reversal of glycolysis close to 20 per cent. Studies with 14C-labeled glucose have shown that the action of DTT + NADP + + ATP on metabolically inert 2-PDS-treated cells restores the production of CO 2 from the C 1 of glucose at a rate almost double that of untreated cells, both aerobically and anaerobically. The same compounds cause 2-PDS-inhibited cells to produce amounts of CO 2 from the C 6 of glucose equal to about 40 per cent that of untreated cells (aerobically). A mixture of DTT + NADP + + ATP, when acting on previously untreated cells, stimulates about threefold the production of CO 2 from the C 1 of glucose, both aerobically and anaerobically. The same mixture inhibits the aerobic production of CO 2 from the C 6 of glucose about 55 per cent. On treatment of Ehrlich ascites cells with 2-PDS, a rapid evolution of CO 2 from the C 1 of glucose occurs, and ceases abruptly after about 5 min. This is consistent with our previous finding that 2-PDS mediates the direct oxidation of glucose 6-phosphate.