The specificity and multiplicity of human placental xenobiotic-metabolizing monooxygenase system studied by potential substrates, inhibitors and gel electrophoresis.
The specificity of the placental monooxygenase system to metabolize foreign compounds was studied by using different potential substrates and inhibitors and by performing electrophoresis of placental microsomes. Placental preparations from smokers catalyzed benzo(a)pyrene hydroxylation, 7-ethoxycoumarin O-deethylation and 2,5-diphenyloxazole hydroxylation, but not biphenyl hydroxylation at 2-, 3- or 4-carbon, aldrin epoxidation to dieldrin or coumarin hydroxylation or aminopyrine N-demethylation. Enzyme activities were inhibited by alpha-naphthoflavone, but to a much lesser extent by SKF 525-A or metyrapone. Correlations between the metabolism of benzo(a)pyrene, 7-ethoxycoumarin and 2,5-diphenyloxazole were highly significant. There was a clear difference in Michaelis-Menten constant of 7-ethoxycoumarin O-deethylation between placentas from smokers and nonsmokers. Gel electrophoresis revealed that protein bands of placental microsomes in the region of cytochrome P-450 enzymes were less prominent than those of rat liver microsomes, a finding that accorded with the relative amounts of cytochrome P-450. There were no consistent differences in the electrophoretic pattern between placentas of variable benzo(a)pyrene hydroxylase activities. Results show that the human placental monooxygenase system is restricted in substrate specificity, that there may be a qualitative difference between smokers and nonsmokers and that the increase in several enzyme activities by cigarette smoking cannot be detected by the standard gel electrophoresis.
D000452:Aldrin / Q000378:metabolism; D000632:Aminopyrine / Q000378:metabolism; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism*; D001580:Benzopyrenes / Q000378:metabolism; D001711:Biotransformation; D001713:Biphenyl Compounds / Q000378:metabolism; D003374:Coumarins / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D008861:Microsomes / Q000201:enzymology / Q000378:metabolism; D010920:Placenta / Q000201:enzymology / Q000378:metabolism*; D011247:Pregnancy; D011335:Proadifen / Q000494:pharmacology; D012907:Smoking / Q000503:physiopathology
D001580:Benzopyrenes; D001713:Biphenyl Compounds; D003374:Coumarins; D005419:Flavonoids; D000632:Aminopyrine; C017299:7-ethoxycoumarin; D011335:Proadifen; D001189:Aryl Hydrocarbon Hydroxylases; D000452:Aldrin