Novel vitamin D photoproducts and their precursors in the skin.
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.
Department of Pathology and Laboratory Medicine; Center for Cancer Research; University of Tennessee Health Science Center; Memphis, TN USA.
Andrzej
A
Slominski
Department of Pathology and Laboratory Medicine; Center for Cancer Research; University of Tennessee Health Science Center; Memphis, TN USA.
Tae-Kang
TK
Kim
Department of Histology; Medical University of Gdańsk; Gdańsk, Poland.
Michal A
MA
Zmijewski
Department of Pathology and Laboratory Medicine; Center for Cancer Research; University of Tennessee Health Science Center; Memphis, TN USA.
Zorica
Z
Janjetovic
Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN USA.
Wei
W
Li
Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN USA.
Jianjun
J
Chen
Department of Biochemistry; Belarusian State University; Minsk, Belarus.
Ekaterina I
EI
Kusniatsova
Department of Biochemistry; Belarusian State University; Minsk, Belarus.
Igor
I
Semak
Department of Medicine, Division of Connective Tissue Diseases; University of Tennessee Health Science Center; Memphis, TN USA.
Arnold
A
Postlethwaite
Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN USA.
Duane D
DD
Miller
Department of Pharmacognosy and Research Institute of Pharmaceutical Sciences; School of Pharmacy; University of Mississippi; University, MS USA.
Jordan K
JK
Zjawiony
School of Chemistry and Biochemistry; University of Western Australia; Crawley, WA, Australia.
Robert C
RC
Tuckey
5,7-dienes; dermal fibroblasts; keratinocytes; melanocytes; melanoma cells; skin; vitamin D