Enzymatic Metabolism of Ergosterol by Cytochrome P450scc to Biologically Active 17α,24-Dihydroxyergosterol

A. Slominski, I. Semak, J. Zjawiony, J. Wortsman, Michael Gandy, J. Li, B. Zbytek, W. Li, Robert Tuckey

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

We demonstrate the metabolism of ergosterol by cytochrome P450scc in either a reconstituted system or isolated adrenal mitochondria. The major reaction product was identified as 17 alpha,24-dihydroxyergosterol. Purified P450scc also generated hydroxyergosterol as a minor product, which is probably an intermediate in the synthesis of 17 alpha,24-dihydroxyergosterol. In contrast to cholesterol and 7-dehydrocholesterol, cleavage of the ergosterol side chain was not observed. NMR analysis clearly located one hydroxyl group to C24, with evidence that the second hydroxyl group is at C17.17 alpha,24-Dihydroxyergosterol inhibited cell proliferation of HaCaT keratinocytes and melanoma cells. Thus, in comparison with cholesterol and 7-dehydrocholesterol, the 24-methyl group and the C22-C23 double bond of ergosterol prevent side chain cleavage by P450scc and change the enzyme's hydroxylase activity from C22 and C20, to C24 and C17, generating bioactive product.
Original languageEnglish
Pages (from-to)931-939
JournalChemistry & Biology
Volume12
Issue number8
DOIs
Publication statusPublished - 2005

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