An alternative pathway of vitamin D2 metabolism

Cytochrome P450scc (CYP11A1)-mediated conversion to 20-hydroxyvitamin D2 and 17,20-dihydroxyvitamin D2

Andrzej Slominski, Igor Semak, Jacobo Wortsman, Jordan Zjawiony, Wei Li, Blazej Zbytek, Robert C. Tuckey

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

We report an alternative, hydroxylating pathway for the metabolism of vitamin D2 in a cytochrome P450 side chain cleavage (P450scc; CYP11A1) reconstituted system. NMR analyses identified solely 20-hydroxyvitamin D2 and 17,20-dihydroxyvitamin D2 derivatives. 20-Hydroxyvitamin D2 was produced at a rate of 0.34 mol·min-1·mol-1 P450scc, and 17,20-dihydroxyvitamin D2 was produced at a rate of 0.13 mol·min-1·mol-1. In adrenal mitochondria, vitamin D2 was metabolized to six monohydroxy products. Nevertheless, aminoglutethimide (a P450scc inhibitor) inhibited this adrenal metabolite formation. Initial testing of metabolites for biological activity showed that, similar to vitamin D2, 20-hydroxyvitamin D2 and 17,20-dihydroxyvitamin D2 inhibited DNA synthesis in human epidermal HaCaT keratinocytes, although to a greater degree. 17,20-Dihydroxyvitamin D 2 stimulated transcriptional activity of the involucrin promoter, again to a significantly greater extent than vitamin D2, while the effect of 20-hydroxyvitamin D2 was statistically insignificant. Thus, P450scc can metabolize vitamin D2 to generate novel products, with intrinsic biological activity (at least in keratinocytes).

Original languageEnglish (US)
Pages (from-to)2891-2901
Number of pages11
JournalFEBS Journal
Volume273
Issue number13
DOIs
StatePublished - Jul 1 2006

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Cholesterol Side-Chain Cleavage Enzyme
Ergocalciferols
Metabolism
Metabolites
Bioactivity
Keratinocytes
Aminoglutethimide
Mitochondria
Dihydroxycholecalciferols
Cytochrome P-450 Enzyme System
Nuclear magnetic resonance
17,20-dihydroxyvitamin D2
20-hydroxyvitamin D2
Derivatives
DNA
Testing

All Science Journal Classification (ASJC) codes

  • Biochemistry

Cite this

An alternative pathway of vitamin D2 metabolism : Cytochrome P450scc (CYP11A1)-mediated conversion to 20-hydroxyvitamin D2 and 17,20-dihydroxyvitamin D2. / Slominski, Andrzej; Semak, Igor; Wortsman, Jacobo; Zjawiony, Jordan; Li, Wei; Zbytek, Blazej; Tuckey, Robert C.

In: FEBS Journal, Vol. 273, No. 13, 01.07.2006, p. 2891-2901.

Research output: Contribution to journalArticle

Slominski, Andrzej ; Semak, Igor ; Wortsman, Jacobo ; Zjawiony, Jordan ; Li, Wei ; Zbytek, Blazej ; Tuckey, Robert C. / An alternative pathway of vitamin D2 metabolism : Cytochrome P450scc (CYP11A1)-mediated conversion to 20-hydroxyvitamin D2 and 17,20-dihydroxyvitamin D2. In: FEBS Journal. 2006 ; Vol. 273, No. 13. pp. 2891-2901.
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