Genes and different vitamin D related substances in the skin

Created April 2013

Novel vitamin D photoproducts and their precursors in the skin

Dermato Endencronology Volume 5, Issue 1 January/February/March 2013

http://dx.doi.org/10.4161/derm.23938

Keywords: 5,7-dienes, dermal fibroblasts, keratinocytes, melanocytes, melanoma cells, skin, vitamin D

Authors: Andrzej T. Slominski, Tae-Kang Kim, Michal A. Zmijewski, Zorica Janjetovic, Wei Li, Jianjun Chen, Ekaterina I. Kusniatsova, Igor Semak, Arnold Postlethwaite, Duane D. Miller, Jordan K. Zjawiony and Robert C. Tuckey

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

  1. 7DHC

  2. 22(OH)7DHC

  3. 20,22(OH)27DHC

  4. 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.

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See also VitaminDWiki

Tags: Genetics