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 bs, NADPH -cytochrome c reductase, epoxide hydrolase, aryl hydrocarbon hydroxylase, benzphetamine N-demethylase, p-nitroanisole-0-demethylase, ethoxycoumarin-0-deethylase, steroid-16a-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 a-naphthoflavone on 7-ethoxycoumarin-0-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 v i m a-naphthoflavone and metyrapone, the results of steroid metabolism, and slab gel electrophoresis are strong indications for multiplicity of human liver cytochrome P-450.Without appropriate means, living organisms would never be able to eliminate from their systems the lipophilic compounds which are either produced by their own metabolism (i.e. steroid hormones, fatty acids, prostaglandins), or are accidentally or voluntarily absorbed from their environment (i.e. food additives, drugs, pesticides, pollutants . . .). Living organisms have thus developed a number of enzymic systems which transform these substances into more polar and therefore more hydrophilic metabolites which can be easily excreted via the urine or feces.The first step in these metabolic transformations is usually catalyzed by (cytochrome P-450)-dependent monooxygenases. These microsomal multienzyme complexes oxidize a great variety of endogenous as well as exogenous substrates. Their biochemical and biological properties have been extensively studied in laboratory animals [l -41. The different types of cytochrome P-450 are characterized by their substrate specificity. Their qualitative and quantitative proportions in a given tissue vary largely as a function of physiological, pharmacological and pathological parameters [2,3,5].Trivia! Numes. r-Naphthoflavone, 7,8-benzoflavone; rnetyrapone, 2-methyl-1,2-di-3-pyridyl-l -propanone; progesterone, pregn-4-en-3,20-dione; pregnenolone, 3p-hydroxypregn-5-en-20-one; testosterone, androst-4-en-I7f1'-01-3-one; dehydroepiandrosterone, 3p-hydroxyandrost-5-en-1 7-one; estradiol...
