Abstract
1) Hepatic cytochrome P[450] and b5 concentrations and the activity of NADPH-cytochrome c reductase, six mixed function oxidase enzymes (ethylmorphine N-demethylase, biphenyl 2-, 3- and 4-hydroxylases, ethoxyresrufin O-deethylase and benzo(a)pyrene hydroxylase) and two non-mixed function oxidase enzymes (UDPGA tranferase and alcohol dehydrogenase) were determined in vitro in 15 different mammalian species (ranging in body weight from mouse to man) and 4 rat strains. The kinetics of the binding of hexobarbital (type 1 substrate) and aniline (type 2 substrate) (Ks and Amax) to cytochrome ,P[450] were also determined in liver microsomal preparations of most of these animal species and rat strains, Aminopyrine N-demethylase and biphenyl 4-hydroxylase activities in vivo were determined in 6 animal species (ranging in body weight from mouse to rabbit) and in the 4 rat strains. The possible relationship between species differences in these parameters and body weight and the importance of strain differences were determined. 2) Species differences in cytochrome P450 levels, ethylmorphine N-demethylase, and biphenyl 2-, 3-and 4-hydroxylase activities in vitro showed a signficant inverse correlation with body weight (on a logarithmic scale). No such relationship was seen with the other enzymes studied. A significant direct correlation with body weight was seen with aniline A[max]. Studies in vivo showed a highly significant inverse correlation between body weight and both aminopyrine N-demethylase and biphenyl 4-hydroxylase activities (logarithmic scale). 3) Strain differences in vitro were small compared to species differences for the cytochrome P[450] mediated enzymes. Whereas for the enzymes catalysed by the P[448] forms of cytochrome P450 the fold variation between strain and species differences were smaller. In vivo the strain differences were much smaller than the species differences. 4) Determination of the rank order of species differences for the different parameters studied showed many significant correlations between parameters which may indicate the involvement of common rate-limiting factors in different enzyme reactions.