Species and phenobarbitone-induced differences in the kinetic constants of liver microsomal harmine O-demethylation.
1. The apparent kinetic constants for the O-demethylation of harmine to harmol by 10 000 g supernatant fractions from livers of mice, rats, guinea-pigs, rabbits, cats and cows have been determined. The Km values were 10-39 muM and Vmax 0-25 and 1-65 nmol/mg protein/min. 2. Optimal conditions of incubation time and NADP requirements differed between species. In all species except cat and cow the rate of O-demethylation of harmine was linear for 5 min, but in the latter species was linear for 15 min. Maximum stimulation of O-demethylation occurred at NADP concn. of between 50 and 375 muM. 3. Phenobarbitone pre-treatment of weanling, young adult and mature adult mice increased the Vmax for O-demethylation by 2.9- to 4.6-fold but did not change Km. Increased Vmax values were greatest in young and least in old mice and these changes were directly correlated with a decrease of hexobarbitone sleeping time.
D000818:Animals; D002415:Cats; D002417:Cattle; D006168:Guinea Pigs; D006247:Harmine / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D009249:NADP / Q000494:pharmacology; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D012890:Sleep / Q000187:drug effects; D013045:Species Specificity
D006247:Harmine; D009249:NADP; D010089:Oxidoreductases, N-Demethylating; D010634:Phenobarbital