NAD(P)H utilization in the reduction of pyruvate to lactate in a glycogen-containing subline of Ehrlich ascites tumour cells.
The possible pathways of utilization of glucose-6-phosphate (G-6-P) produced from glycogen breakdown have been investigated in a glycogen-containing subline of Ehrlich ascites tumour cells. Addition of either mitochondrial inhibitors or pyruvate to ascites cells metabolizing endogenous substrates enhances the rate of lactate production. However, only in the former condition such effect is abolished by iodoacetate (IAA). In pyruvate-supplemented cells mitochondrial inhibitors cause a further increase in lactate production which becomes insensitive to IAA when the cells are depleted of endogenous substrates. Measurements of the glycogen content show that either in the presence of mitochondrial inhibitors or pyruvate there is a stimulation of glycogenolysis. Significant changes (about 10--20 fold increase) of the G-6-P level are observed only in the presence of both mitochondrial inhibitors and IAA, irrespective of pyruvate addition. However, with pyruvate the accumulation of G-6-P becomes lower if the cells are starved. The results obtained indicate that in our conditions G-6-P which is produced during glycogenolysis may be oxidized either through the Embden-Meyerhof pathway or the phosphogluconate pathway. Indeed, whereas mitochondrial inhibitors promote the utilization of this metabolite through the first route by enhancing the activity of phosphofructokinase, added pyruvate favours the other route by lowering the cytosolic NADPH/NADP+ ratio.
D000693:Anaerobiosis; D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism*; D005942:Gluconates / Q000378:metabolism; D005958:Glucosephosphates / Q000378:metabolism*; D006003:Glycogen / Q000378:metabolism*; D006019:Glycolysis; D007773:Lactates / Q000096:biosynthesis; D051379:Mice; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D010085:Oxidative Phosphorylation; D011773:Pyruvates / Q000378:metabolism
D005942:Gluconates; D005958:Glucosephosphates; D007773:Lactates; D011773:Pyruvates; D009243:NAD; D009249:NADP; D006003:Glycogen