Microsomes were prepared from human livers obtained from renal donors of various ages
and both sexes. Their drug-metabolizing capacity was measured and compared to that
of rat liver microsomes. The following parameters were investigated: cytochrome P-450,
cytochrome B5, NADPH-cytochrome c reductase, epoxide hydrolase, aryl hydrocarbon hydroxylase,
benzphetamine N-demethylase, p-nitroanisole-O-demethylase, ethoxycoumarin-O-deethylase,
steroid-16 alpha-hydroxylase. In addition, the metabolism of benzo(a)pyrene, progesterone,
pregnenolone, testosterone, dehydroepiandrosterone and estradiol was studied in detail
in vitro. The inhibitory effect of metyrapone and alpha-naphthoflavone on 7-ethoxycoumarin-O-deethylase
was measured. The microsomal proteins of both species were separated by polyacrylamide
gel electrophoresis in the presence of dodecyl sulfate. The following conclusions
were drawn from the results obtained. Human liver microsomes can be stored under optimal
conditions for the measurement of a large variety of enzymic activities. Human liver
microsomes are able to metabolize the various xenobiotics used as substrates with
a rate similar to that of female rat liver microsomes. No sex-linked difference in
enzymic activity was observed in human microsomes. Significant differences in benzo(a)pyrene
and steroid metabolism were registered when human and rat liver microsomes were compared.
The monooxygenase activities, the sensitivity to in vitro alpha-naphthoflavone and
metyrapone, the results of steroid metabolism, and slab gel electrophoresis are strong
indications for multiplicity of human liver cytochrome P-450.