Effect of nicotinamide administration to rats on the liver microsomal drug metabolizing enzymes.
A single injection or 3 successive injections of nicotinamide (500 mg/kg body wt) increased NADPH-cytochrome c reductase and aniline hydroxylase activities of rat liver microsomes without changing cytochrome P-450 content. Oral administration of nicotinamide for 2 weeks resulted in significant increase in cytochrome P-450, indicating that nicotinamide was an inducer of cytochrome P-450 though its potency was weak. A kinetic study indicated that microsomes isolated from control rats contained only high affinity (low Km) form of aniline hydroxylase while microsomes isolated from nicotinamide-treated rats contained more high affinity form and a newly appeared-low affinity (high Km) form. These results suggest that there exist at least 2 different cytochrome P-450s participating in aniline hydroxylation in rat liver microsomes and nicotinamide induces the high Km form. Ethanol or nicotinamide consumption for 2 weeks resulted in enhancement of high affinity form and appearance of low affinity form but with slightly different Km values.
D000633:Aminopyrine N-Demethylase / Q000032:analysis; D000815:Aniline Hydroxylase / Q000032:analysis; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis; D004790:Enzyme Induction / Q000187:drug effects; D008658:Inactivation, Metabolic; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D009251:NADPH-Ferrihemoprotein Reductase / Q000032:analysis; D009536:Niacinamide / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D009536:Niacinamide; D003577:Cytochrome P-450 Enzyme System; D000815:Aniline Hydroxylase; D000633:Aminopyrine N-Demethylase; D009251:NADPH-Ferrihemoprotein Reductase