The constitutive 7-ethoxycoumarin O-deethylase activity of human placental microsomes: relationship to aromatase.
The constitutive 7-ethoxycoumarin deethylase activity of human placental microsomes from non-smokers was acutely inhibited by a number of androgens which serve as substrates for and/or competitive inhibitors of estrogen synthesis by the aromatase activity of these preparations. 10 beta-(2-Propynyl)estr-4-ene-3,17-dione and 4-hydroxyandrost-4-ene-3,17-dione, androgen derivatives which produce a mechanism-based, time-dependent inactivation of placental aromatase caused a cofactor-dependent decay in deethylase activity which paralleled the loss of aromatase activity caused by these agents and which was antagonized by aromatase substrates. Conversely, 7-ethoxycoumarin antagonized the time-dependent action of 10 beta-(2-propynyl)estr-4-ene-3,17-dione and 4-hydroxyandrost-4-ene-3,17-dione on aromatase and inhibited competitively the aromatization of 4-androstene-3,17-dione. The Ki for 7-ethoxycoumarin was equivalent to its Km as substrate for deethylation. It is concluded that a common oxidase species is responsible for both the aromatase and constitutive 7-ethoxycoumarin deethylase activities of human placental microsomes.
D015660:7-Alkoxycoumarin O-Dealkylase; D000728:Androgens / Q000494:pharmacology; D001141:Aromatase / Q000378:metabolism*; D005260:Female; D006801:Humans; D007700:Kinetics; D008861:Microsomes / Q000201:enzymology*; D010105:Oxygenases / Q000378:metabolism*; D010920:Placenta / Q000201:enzymology*; D011247:Pregnancy
D000728:Androgens; D010105:Oxygenases; D015660:7-Alkoxycoumarin O-Dealkylase; D001141:Aromatase