May 1, 1976

Species and phenobarbitone-induced differences in the kinetic constants of liver microsomal harmine O-demethylation

Xenobiotica; the Fate of Foreign Compounds in Biological Systems
M D Burke, D G Upshall

Abstract

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.

  • References10
  • Citations8

Mentioned in this Paper

Sleep, Slow-Wave
Harmine
Microsomes, Liver
Oxidoreductases, N-Demethylating
NADP
Bos indicus
Luminal
Cavia porcellus
Felis catus

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