Adaptational changes in kinetic parameters of G6PDH but not of PGDH during contamination-induced carcinogenesis in livers of North Sea flatfish.
Kinetic parameters of glucose-6-phosphate dehydrogenase (G6PDH) and phosphogluconate dehydrogenase (PGDH) were determined in situ in livers of marine flatfish flounder that were caught in unpolluted areas in the open sea and in the highly polluted river Elbe (Germany). Analysis was performed quantitatively in liver sections using valid enzyme histochemical methods and image analysis. G6PDH but not PGDH was strongly affected by contaminant exposure and subsequent carcinogenesis. G6PDH showed a gradual decrease in Vmax and Km for glucose-6-phosphate in extralesional normal-looking liver tissue. Hepatocellular carcinomas also showed a low Km, whereas the Vmax was upregulated. These findings are interpreted as follows: prolonged challenges of the livers by pollutants inhibit or inactivate G6PDH and this is compensated for by reduction in Km. In carcinomas, G6PDH levels are upregulated but the low Km values are kept to increase the NADPH production capacity required in cancer cells showing that posttranslational regulation processes are important to control cellular metabolism under various environmental conditions.
Van Noorden
C J
CJ
Academic Medical Center, University of Amsterdam, Department of Cell Biology and Histology, The Netherlands. c.j.vannoorden@AMC.UVA.NL
Bahns
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S
Köhler
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A
D000222:Adaptation, Physiological / Q000187:drug effects*; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000201:enzymology; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005432:Flounder; D005954:Glucosephosphate Dehydrogenase / Q000187:drug effects / Q000378:metabolism*; D006911:Hydroxyprostaglandin Dehydrogenases / Q000187:drug effects / Q000378:metabolism*; D007091:Image Processing, Computer-Assisted; D007700:Kinetics; D008113:Liver Neoplasms / Q000139:chemically induced* / Q000201:enzymology*; D009249:NADP / Q000096:biosynthesis; D009659:North Sea; D014877:Water Pollution, Chemical / Q000009:adverse effects*
D009249:NADP; D006911:Hydroxyprostaglandin Dehydrogenases; D005954:Glucosephosphate Dehydrogenase