| Popis: |
Intermediate steps in the aromatization of 4-androstene-3,17-dione to estrone, catalyzed by human placental microsomes, have been evaluated through the use of normal and hypothetical intermediate compounds as substrates and the oxidases involved have been characterized by the effects of oxygen and carbon monoxide upon these conversions. When air was replaced by a 5% oxygen-95% nitrogen atmosphere, the rate of aromatization of 4-androstene-3,17-dione or of 19-hydroxy-4-androstene-3,17-dione was reduced 30 to 35% while no inhibition occurred if 3,17-dioxo-4-androsten-19-al was the substrate. The aromatization of all three of these steroids in 5% oxygen was not inhibited when carbon monoxide was added at a concentration 8.8 times that of oxygen. However, this same CO:O2 ratio of 8.8 decreased the aromatization of 4-estrene-3,17-dione 51 to 95% and the aromatization of 1,4-androstadiene-3,17-dione 10 to 16%. Hydroxylation of the A ring of 4-estrene-3,17-dione was also inhibited by carbon monoxide to the same extent as was its aromatization. These findings have been interpreted as evidence for the existence of three mixed function oxidases active in steroid aromatization, one of which may be a form of cytochrome P-450. |
