Novel vitamin D photoproducts and their precursors in the skin

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

Research output: Contribution to journalReview article

34 Citations (Scopus)

Abstract

Novel metabolic pathways initiated by the enzymatic action of CYP11A1 on 7DHC (7-dehydrocholesterol), ergosterol, vitamins D3 and D 2 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.

Original languageEnglish (US)
Pages (from-to)7-19
Number of pages13
JournalDermato-Endocrinology
Volume5
Issue number1
DOIs
StatePublished - Jan 1 2013

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Cholesterol Side-Chain Cleavage Enzyme
Secosteroids
Vitamin D
Ergocalciferols
Cholecalciferol
Skin
25-Hydroxyvitamin D3 1-alpha-Hydroxylase
Ergosterol
Calcitriol Receptors
Metabolic Networks and Pathways
Psoriasis
Mass Spectrometry
Enzymes
7-dehydrocholesterol
Neoplasms
Therapeutics

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Dermatology

Cite this

Slominski, A. T., Kim, T. K., Zmijewski, M. A., Janjetovic, Z., Li, W., Chen, J., ... Tuckey, R. C. (2013). Novel vitamin D photoproducts and their precursors in the skin. Dermato-Endocrinology, 5(1), 7-19. https://doi.org/10.4161/derm.23938

Novel vitamin D photoproducts and their precursors in the skin. / Slominski, Andrzej T.; Kim, Tae Kang; Zmijewski, Michal A.; Janjetovic, Zorica; Li, Wei; Chen, Jianjun; Kusniatsova, Ekaterina I.; Semak, Igor; Postlethwaite, Arnold; Miller, Duane; Zjawiony, Jordan K.; Tuckey, Robert C.

In: Dermato-Endocrinology, Vol. 5, No. 1, 01.01.2013, p. 7-19.

Research output: Contribution to journalReview article

Slominski, AT, Kim, TK, Zmijewski, MA, Janjetovic, Z, Li, W, Chen, J, Kusniatsova, EI, Semak, I, Postlethwaite, A, Miller, D, Zjawiony, JK & Tuckey, RC 2013, 'Novel vitamin D photoproducts and their precursors in the skin', Dermato-Endocrinology, vol. 5, no. 1, pp. 7-19. https://doi.org/10.4161/derm.23938
Slominski AT, Kim TK, Zmijewski MA, Janjetovic Z, Li W, Chen J et al. Novel vitamin D photoproducts and their precursors in the skin. Dermato-Endocrinology. 2013 Jan 1;5(1):7-19. https://doi.org/10.4161/derm.23938
Slominski, Andrzej T. ; Kim, Tae Kang ; Zmijewski, Michal A. ; Janjetovic, Zorica ; Li, Wei ; Chen, Jianjun ; Kusniatsova, Ekaterina I. ; Semak, Igor ; Postlethwaite, Arnold ; Miller, Duane ; Zjawiony, Jordan K. ; Tuckey, Robert C. / Novel vitamin D photoproducts and their precursors in the skin. In: Dermato-Endocrinology. 2013 ; Vol. 5, No. 1. pp. 7-19.
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