The substituted pyridines metyrapone and nicotinamide are inducers of 5-aminolevulinate synthase and cytochrome P-450 in hepatocyte culture.
The effects of metyrapone and nicotinamide, two substituted pyridines, were studied in cultured chick embryo hepatocytes, a system characterized by preserved inducibility of cytochrome P-450 hemoproteins. Both metyrapone and nicotinamide caused a dose-dependent increase in cytochrome P-450 concentration. Their inducing potencies differed by one to two orders of magnitude and correlated with the known difference in the binding affinity of these two pyridines to cytochrome P-450. The increase of cytochrome P-450 concentration after metyrapone and nicotinamide was additive to the induction of cytochrome P-450 by phenobarbital and beta-naphthoflavone and was abolished by cycloheximide. Treatment of hepatocyte cultures with metyrapone resulted in an increase in a microsomal protein with an apparent mol. wt of 52,000. In addition, induction of cytochrome P-450 by the substituted pyridines was associated with enhanced 5-aminolevulinate synthase, the rate-limiting enzyme of heme biosynthesis. These data suggest that in cultured chick embryo hepatocytes the substituted pyridines metyrapone and nicotinamide induce cytochrome P-450.
D000624:5-Aminolevulinate Synthetase / Q000096:biosynthesis*; D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004790:Enzyme Induction; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008797:Metyrapone / Q000494:pharmacology*; D009536:Niacinamide / Q000494:pharmacology*
D009536:Niacinamide; D003577:Cytochrome P-450 Enzyme System; D000624:5-Aminolevulinate Synthetase; D008797:Metyrapone