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.
Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
F C
FC
Kauffman
R K
RK
Evans
L A
LA
Reinke
S A
SA
Belinsky
C
C
Ballow
R G
RG
Thurman
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D005260:Female; D007521:Isocitrate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008291:Malate Dehydrogenase / Q000378:metabolism; D008748:Methylcholanthrene / Q000494:pharmacology*; D009243:NAD / Q000378:metabolism*; D009249:NADP / Q000378:metabolism*; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000378:metabolism*; D010477:Perfusion; D010734:Phosphogluconate Dehydrogenase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D009243:NAD; D009249:NADP; D008748:Methylcholanthrene; D000255:Adenosine Triphosphate; D010088:Oxidoreductases; D008291:Malate Dehydrogenase; C030574:malate dehydrogenase (decarboxylating); D007521:Isocitrate Dehydrogenase; D010734:Phosphogluconate Dehydrogenase