Effects of 3-methylcholanthrene on oxidized nicotinamide-adenine dinucleotide phosphatedependent dehydrogenases and selected metabolites in perfused rat liver.

Treatment of adult rats with 3-methylcholanthrene over a 3-day period produced significant decreases in hepatic ATP concentrations and elevated the activities of 6-phosphogluconate dehydrogenase and malic enzyme. The decline in ATP was accompanied by a decrease in total adenine nucleotides; however, ATP/ADP ratios were essentially the same in livers of normal and 3-methylcholanthrene-treated rats, and no significant changes were noted in glycolytic and citric acid cycle intermediates. Thus, hepatic energy metabolism does not appear to be altered grossly after 3-methylcholanthrene treatment. NADP(+)/NADPH ratios calculated from substrates assumed to be in near equilibrium with malic enzyme, isocitrate dehydrogenase and 6-phosphogluconate dehydrogenase increased after 3-methylcholanthrene treatment; these changes were accompanied by significant increases in the activity of malic enzyme and 6-phosphogluconate dehydrogenase. Oxidation of hepatic NADPH and elevation of activities of several NADPH-generating enzymes by 3-methylcholanthrene indicates that this agent which induces components of the mixed-function oxidase system also elevates the capacity of the liver to form NADPH.