Control Mechanisms of Glycolysis in Ehrlich Ascites Tumor Cells.

Studies on the rate-limiting factors of glycolysis in Ehrlich ascites tumor cells have indicated that orthophosphate is the major rate-limiting factor for glycolysis (l-5). Pi presumably influences the rate of glyceraldehyde 3-phosphate dehydrogenase, the only glycolytic enzyme known to require Pi. However, recent reports have indicated that Pi may have other important effects on glycolytic systems. Thus, in cell-free systems, Passonneau and Lowry (6) as well as Mansour (7) showed that Pi may activate P-fructokinase by counteracting the inhibitory effect of high ATP concentrations. Rose, Warms, and O’Connell (8, 9) have reported that Pi may partially relieve the glucose-6-P inhibition of hexokinase in red blood cells. In the light of these observations intact ascites tumor cells were re-examined in order to define more precisely the site of action of Pi in the control of intracellular glycolysis. In addition, other factors which influence the rate of glycolysis, such as the availability of glucose, have been analyzed. The data to be reported in this communication revealed that the availability of glucose restricted aerobic but not anaerobic glycolysis at glucose concentrations below 1.2 mM. The primary effect of Pi appeared to be mediated through its influence on P-fructokinase, although hexokinase and glyceraldehyde-3-P dehydrogenase were also affected. A preliminary report has appeared (10).