Alterations in the glycolytic and glutaminolytic pathways after malignant transformation of rat liver oval cells

Oval cells are liver epithelial cells that proliferate during the early sta ges of hepatocarcinogenesis induced by a variety of chemicals. The oval cel l lines OC/CDE 6 and OC/CDE 22 have been established in our laboratory at t wo time points (6 and 22 weeks) of the carcinogenic process and have been m alignantly transformed by different procedures. During the transformation p rocess, the glycolytic and glutaminolytic flux rates were consistently up-r egulated and this process was accompanied by an overproportional increase i n the activities of cytosolic hexokinase and 6-phosphogluconate dehydrogena se. In transformed oval cells, a strong correlation between the glycolytic flux rate and glutamine consumption as well as glutamate production was obs erved. Furthermore, the transport of glycolytic hydrogen, produced by the g lyceraldehyde 3-phosphate dehydrogenase-catalyzed reaction, from the cytoso l into the mitochondria by means of the malate-aspartate shuttle was enhanc ed, this being due to alterations in the activities of malate dehydrogenase and glutamate oxaloacetate transaminase. The up-regulation of the glycolyt ic hydrogen transport and the alterations in the glycolytic enzyme complex led to an enhanced pyruvate production at high glycolytic flux rates. Taken together, our data are further proof that a special metabolic feature (inc reased glycolysis and glutaminolysis) is characteristic for tumor cells and that the mechanism by which this metabolic state is induced can be totally different. J. Cell. Physiol. 181:136-146, 1999. (C) 1999 Wiley-Liss, Inc.