title: Evidence of an enzymatic 17alpha leads to 21 hydroxyl transfer in the biosynthesis of cortexolone from 17alpha-hydroperoxyprogesterone by adrenal cortex microsomes.
abstract: The concept of a possible biogenetic intramolecular relationship between several pairs of hydroxylated positions of corticosteroids, in particular between positions 17alpha and 21, has been proposed by us some time ago. We now present evidence that to a certain extent such a relationship can indeed exist. 18O-labelled 17alpha-hydroperoxyprogesterone was incubated under ordinary oxygen atmosphere with the microsomal fractions of bovine adrenal cortex. Following extensive purifications by thin-layer chromatography, we have isolated a metabolite with mobility characteristics corresponding to those of authentic 17,21-dihydroxy-4-pregnene-3,20-dione (cortexolone). According to its mass spectrum, this metabolite has a molecular weight of 350, i.e. 4 atomic mass units higher than the molecular weight of non-labelled cortexolone. No conversion of 17alpha-hydroperoxyprogesterone to cortexolone was observed with a previously heat-inactivated preparation. The presence of 4 additional mass units in the cortexolone metabolite means that the latter has preserved two 18O-labels in the molecule, one at position 17alpha and the other one at position 21. This can only be explained by a rearrangement reaction of the hydroperoxide group in such a way that it is accompanied by a C-17alpha to C-21 hydroxyl transfer. In the inverse case, when non-labelled 17alpha-hydroperoxyprogesterone was incubated under 99% 18O2-atmosphere, non-labelled cortexolone of molecular weight 346 was also found.
mesh_terms: D015065:17-Hydroxycorticosteroids / Q000096:biosynthesis*; D000302:Adrenal Cortex / Q000201:enzymology*; D000311:Adrenal Glands / Q000201:enzymology*; D000818:Animals; D002417:Cattle; D003350:Cortodoxone / Q000096:biosynthesis*; D006908:Hydroxyprogesterones / Q000378:metabolism; D013058:Mass Spectrometry; D008861:Microsomes / Q000201:enzymology; D011374:Progesterone / Q000031:analogs & derivatives* / Q000378:metabolism; D013250:Steroid Hydroxylases / Q000378:metabolism*
chemical_list: D015065:17-Hydroxycorticosteroids; D006908:Hydroxyprogesterones; C002175:progesterone 17 alpha-hydroperoxide; D011374:Progesterone; D013250:Steroid Hydroxylases; D003350:Cortodoxone