The Relationship between Cell Membrane Potassium Ion Transport and Glycolysis

Abstract

Cell membrane transport of K + stimulates the rate of glycolysis in Ehrlich ascites tumor cells. A study of the characteristics of this relationship indicates that the stimulation occurs under anaerobic as well as under aerobic conditions. The data suggest that glycolysis is stimulated by a K + transport mechanism that is coupled to Na + transport because the effect is blunted or abolished when the principal intracellular ion is lithium or choline. This stimulus to glycolysis is blocked by ouabain and ethacrynic acid, agents that have been shown to inhibit monovalent cation transport in erythrocytes. In contrast to the action of ouabain, glycolysis is inhibited by ethacrynic acid in Ehrlich ascites tumor cells in the absence of cell membrane K + transport. In studies with ghost-free hemolysates of human erythrocytes and with cytosol prepared from Ehrlich ascites tumor cells, ethacrynic acid significantly blocks lactate formation from fructose diphosphate demonstrating the direct inhibitory effect of this agent on one or more enzymes of the Embden-Meyerhof pathway. Since ethacrynic acid has no influence on lactate formation in intact erythrocytes utilizing an endogenous substrate, the presumptive site of inhibition is proximal to the 3-phosphoglycerate level.

Reversal of Cyclic AMP-Mediated Intestinal Secretion by Ethacrynic Acid

“…Recent investigations on the effect of EA on energyyielding reactions show that in several systems, e.g., renal cortex (30), renal medulla (30), Ehrlich asictes tumior cells (31), and turtle bladder epithelium (30), EA was shown to affect a step in the glycolytic chain beyond formation of fructose diphosphate. In the turtle bladder, it was further demonstrated that EA inhibits glyceraldehyde-3-plhosphate dehydrogenase activity (30).…”

Sulphydryl requirement for insulin release from the perfused pancreas

“…The slow inhibitory action of EA on insulin secretion may be due to a slow penetration of this drug into the beta cell, where it probably binds to SH groups of enzymes of glycolysis and oxidative phosphorylation, as demonstrated in cell free preparations [17,18] and in intact cells [19][20][21]. Slow penetration into the beta-cell could be measured for other SH-groups blocking agents [5,[22][23][24].…”

The Effect of Ouabain and Ethacrynic Acid on ATPase Activities in the Inner Ear of the Rat and Guinea Pig

“…Ethacrynic acid causes a rapid fall in ATP of kidney slices (Epstein, 1972b) and rat uterus (Daniel et al, 1971). Therefore the inhibitory effect of ethacrynic acid on transport processes can just as well be explained by its inhibition of ATP production both from oxidative phosphorylation and glycolysis (Gordon, 1968;Gordon and den Hartog, 1969;Daniel et al, 1971;Klahr et al, 1971) as by a direct inhibitory effect on Na-K-ATPase. According to these observations and the results presented in figures 1 a, b, it seems unlikely that the depressive effect of ethacrynic acid using a 10~4 M concentration on the ERP and CMP found in guinea pigs and rats (Prazma et al, \912\Bosher et al, 1973;Thalmann et al, 1973), can be attributed to a specific effect of ethacrynic acid on this enzyme system.…”