Comparison of cytochrome P-450 content and activities in liver microsomes of seven animal species, including man

Abstract

1. The cytochrome P-450 content found in human livers obtained post mortem was between 0.21–0.42 nmol/mg protein. 2. The kinetic parameters of the mono-oxygenase activities—K_m and V_max—were determined in liver microsomes for N-demethylation (aminopyrine, benzphetamine, ethylmorphine), O-demethylation (4-nitroanisole), O-deethylation (7-ethoxycoumarin) and hydroxylation (benzo[a]pyrene), in an attempt to establish an inter-species comparison between man and the six animal species studied. 3. The four substrates studied (aminopyrine, benzphetamine, ethylmorphine, benzo[a]pyrene) were shown to be less active in humans than the male rat, which is the most commonly used model. However, other animal species, such as the female Sprague-Dawley rat and the pig, are much more similar to man. 4. From a procedural point of view, the optimal substrate concentrations vary from one experimental species to another. Due to the apparent K_m observed, for example, the activities of the guinea-pig require a higher substrate concentration.