Peroxisome-proliferator regulates key enzymes of the tryptophan-NAD(+) pathway

Structually diverse peroxisome-proliferators (PPs) were investigated regard ing their effects on NAD(+) level and two key enzyme activities in the tryp tophan (Trp)-NAD(+) pathway in the liver of rats (Sprague-Dawley male) fed PP-containing diets freely for 2 weeks. All PPs, except for thyroxine, sign ificantly increased hepatic NAD(+) level in concert with hepatic hypertroph y. Activity of quinolinate phosphoribosyltransferase (QAPRTase), one of the key enzymes in the Trp-NAD(+) pathway, was increased by the PPs which caus ed significant increase in the hepatic NAD(+). On the other hand, alpha-ami no-beta-carboxymuconate-epsilon-semialdehyde decarboxylase (ACMSDase), anot her key enzyme in the Trp-NAD(+) pathway, was drastically inhibited by all PPs except for linolenic acid, which was only slightly inhibitory. Most PPs investigated activated peroxisomal marker enzymes such as palmitoyl CoA ox idase, catalase, and PPAR-alpha(peroxisome-proliferator activated receptor- alpha)-dependent enzymes, such as malic enzyme and L-3-glycerophosphate deh ydrogenase. NAD(+) was also increased in the rat hepatocytes cultured in th e medium supplemented with PPs. These data suggested that regulation of the key enzymes in the Trp-NAD(+) pathway was associated with PPAR-alpha direc tly or indirectly, and as a consequence the hepatic NAD(+) was increased by PPs. (C) 1999 Academic Press.