Abstract

Since the NADP oxidation-reduction system plays a primary role in activating and detoxifying chemical carcinogens, the activities of the hepatic enzymes of the pentose phosphate pathway as well as other cytosolic NADP-linked enzymes were studied in the rat in vivo during the administration of thioacetamide (TAM). Metabolite couples related to the cytosolic and mitochondrial NADP systems were also investigated. Malic enzyme and transaldolase activities were increased earlier than glucose-6-phosphate and 6-phosphogluconate dehydrogenases. Transketolase and soluble NADP-isocitrate dehydrogenase activities did not change significantly during the 8 weeks of the experiment. This pattern of enzyme activities indicates an increased capacity for generation of NADPH and ribose-5-phosphate and is interpreted to favor detoxifying mechanisms and de novo nucleic acid biosynthesis. The state of reduction of the NADP system in TAM-treated livers as calculated by the metabolite indicator method was more oxidized than expected considering the increased capacity for NADPH generation. This finding is interpreted to be the result of a simultaneously increased utilization of NADPH in the synthesis of glutamate as well as in the NADPH-requiring biosynthetic processes.