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Alterations in the glycolytic and glutaminolytic pathways after malignant transformation of rat liver oval cells
Author(s) -
Mazurek Sybille,
Eigenbrodt Erich,
Failing Klaus,
Steinberg Pablo
Publication year - 1999
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/(sici)1097-4652(199910)181:1<136::aid-jcp14>3.0.co;2-t
Subject(s) - glycolysis , glutaminolysis , biochemistry , flux (metallurgy) , hexokinase , biology , lactate dehydrogenase , glutamate dehydrogenase , glyceraldehyde 3 phosphate dehydrogenase , metabolism , microbiology and biotechnology , dehydrogenase , chemistry , enzyme , glutamate receptor , receptor , organic chemistry
Oval cells are liver epithelial cells that proliferate during the early stages of hepatocarcinogenesis induced by a variety of chemicals. The oval cell lines OC/CDE 6 and OC/CDE 22 have been established in our laboratory at two time points (6 and 22 weeks) of the carcinogenic process and have been malignantly transformed by different procedures. During the transformation process, the glycolytic and glutaminolytic flux rates were consistently up‐regulated and this process was accompanied by an overproportional increase in the activities of cytosolic hexokinase and 6‐phosphogluconate dehydrogenase. In transformed oval cells, a strong correlation between the glycolytic flux rate and glutamine consumption as well as glutamate production was observed. Furthermore, the transport of glycolytic hydrogen, produced by the glyceraldehyde 3‐phosphate dehydrogenase‐catalyzed reaction, from the cytosol into the mitochondria by means of the malate‐aspartate shuttle was enhanced, this being due to alterations in the activities of malate dehydrogenase and glutamate oxaloacetate transaminase. The up‐regulation of the glycolytic 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 (increased glycolysis and glutaminolysis) is characteristic for tumor cells and that the mechanisms by which this metabolic state is induced can be totally different. J. Cell. Physiol. 181:136–146, 1999. © 1999 Wiley‐Liss, Inc.