Glycolytic mechanisms in Ehrlich ascites tumor cells—Effects of disulfide derivatives of pyridine

A study was made of the effects of 6,6'-dithiodinicotinic acid (DTDN) and 2,2'-dithiodipyridine (DTDP) on mouse Ehrlich ascites tumor cells. Both drugs inhibited glucose utilization and lactate production under aerobic conditions, DTDP being effective m lower concentrations than DTDN. Both drugs decreased the proportion of utilized glucose that is converted to lactate. This may indicate increased diversion of glucose into the phosphogluconate pathway. DTDN in concentrations inhibiting lactate production to a minimal degree greatly decreased the levels of dihydroxyacetone phosphate and increased those of glyceraldehyde-3-phosphate occurring in the cells after addition of glucose. This effect was not seen with DTDP. The effect of DTDN on the glycolytic intermediates may be due to inhibition of triosephosphate isomerase. Lack of the effect with DTDP may be due to more potent inhibition of an enzyme at a step prior to formation of fructose-l,6-diphosphate. Both drugs inhibit rabbit muscle triosephosphate isomerase in vitro. The drugs decreased the fall of extracellular pH due to lactic acid formation but did not lead to any unusual relationship between extracellular and intracellular pH. Both drugs caused loss of cellular K + but only in concentrations higher than are required for complete suppression of glycolysis.