Aromatization of delta4-androstene-3,17-dione, 19-hydroxy-delta4-androstene-3,17-dione, and 19-oxo-delta4-androstene-3,17-dione at a common catalytic site in human placental microsomes.
Estrogen is believed to be biosynthesized from androstenedione in placental microsomes by a multienzyme pathway in which 19-hydroxyandrostenedione and 19-oxoandrostenedione (or the hydrated form) are obligatory intermediates. However, both 19-hydroxyandrostenedione and 19-oxoandrostenedione competitively inhibited aromatization of androstenedione, and all three steroids were shown to be mutually competitive. 19-Hydroxyandrostenedione and 19-oxoandrostenedione also competed with androstenedione for binding sites in the microsomes at 4 degrees C. In confirmation of the work of Hollander (Hollander, N. (1962), Endocrinology 71, 723-728), and of Osawa and Shibata (Osawa, Y., and Shibata, K., (1973), Abstracts of the 55th Meeting of the Endocrine Society, Abstract 116) when androstenedione and 19-hydroxyandrostenedione were incubated together, both were converted to estrogen, but little androstenedione was converted to 19-hydroxyandrostenedione. Considered together, these results are incompatible with the multienzyme pathway. Rather, these results may be explained by aromatization of androstenedione at a single catalytic site via enzyme-bound transition states. Both proposed intermediates are, according to this view, by-products which can also be aromatized.
D000735:Androstenedione / Q000031:analogs & derivatives* / Q000378:metabolism*; D001665:Binding Sites; D001667:Binding, Competitive; D002250:Carbon Radioisotopes; D005260:Female; D006801:Humans; D007553:Isotope Labeling; D007700:Kinetics; D008433:Mathematics; D008861:Microsomes / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D014316:Tritium
D002250:Carbon Radioisotopes; D014316:Tritium; D000735:Androstenedione; C014142:19-oxo-delta(4) androstene-3,17-dione; C011482:19-hydroxy-4-androstene-3,17-dione