Concerning the pathway from 19-oxoandrost-4-ene-3,17-dione

Article abstract of DOI:10.1016/0039-128X(87)90024-9

The conversion of a molecule of 19-oxoandrost-4-ene-3,17-dione <1a> to estrone <2a> by human placental aromatase requires a molecule of oxygen and NADPH.An atom of this molecule of oxygen is incorporated into the extruded formic acid derived from C-19 af <1a>.It was proposed that the O₂ is utilized for the enzymatic 2β-hydroxylation of <1a> and the released intermediate 2β-hydroxy-19-oxoandrost-4-ene-3,17-dione <5a> aromatizes nonenzymatically.Should <5a> be an obligatory intermediate of estrogen biosynthesis, then all the oxygen of its 2β-hydroxyl must be incorporated into the extruded formic acid.We have previously synthesized <2β-¹⁸O;19-³H><5c> and proved that none of its 2β-¹⁸O was incorporated in the formic acid extruded in the aromatization.On this basis we concluded that <5a> can not be an obligatory precursor of estrogen biosynthesis.The trapping of radioactive androst-4-ene-2β,3β,17β,19-tetrol in a reductively terminated incubation of a mixture of radioactive androst-4-ene-3,17-dione and <5a> with crude placental aromatase was interpreted as evidence in support of the intermediacy of <5a>.We confirmed that the terol can indeed be trapped in the reductively terminated incubations.However, considering that the crude placental enzyme preparation very likely contains numerous activated oxygen species capable of a variety of oxidation reactions, most of which may not be related to estrogen elaboration, and in view of our results qoted above, the origin and the eventual biosynthetic role of the parent compound of the tetrol remains to be determined.