Novel metabolic pathways initiated by the enzymatic action of
CYP11A1 on 7DHC (7-dehydrocholesterol),
ergosterol,
vitamins D3 and D2 were characterized with help of chemical synthesis, UV and mass spectrometry and NMR analyses. The first pathway follows the sequence 7DHC→22(
OH)7DHC → 20,22(
OH)27DHC → 7DHP (7-dehydropregnenolone), which can further be metabolized by steroidogenic
enzymes. The resulting 5,7-dienes can be transformed by UVB to corresponding, biologically active,
secosteroids. Action of
CYP11A1 on
vitamin D3 and D2 produces novel hydroxyderivatives with
OH added at positions C17, C20, C22, C23 and C24, some of which can be hydroxylated by
CYP27B1 and/or by CYP27A1 and/ or by
CYP24A1.The main products of these pathways are biologically active with a potency related to their chemical structure and the target cell type. Main products of CYP11A1-mediated metabolism on
vitamin D are non-calcemic and non-toxic at relatively high doses and serve as partial agonists on the
vitamin D receptor. New
secosteroids are excellent candidates for
therapy of fibrosing, inflammatory or hyperproliferative disorders including
cancers and
psoriasis.