Adaptational changes in kinetic parameters of G6PDH but not of PGDH during contamination-induced carcinogenesis in livers of North Sea flatfish

Abstract 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 V max and K m for glucose-6-phosphate in extralesional normal-looking liver tissue. Hepatocellular carcinomas also showed a low K m , whereas the V max 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 K m . In carcinomas, G6PDH levels are upregulated but the low K m 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.