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Titel: Metabolism of oral turinabol by the human brain cholesterol 24-hydroxylase CYP46A1
VerfasserIn: Putkaradze, Natalia
Hartz, Philip
Hutter, Michael C.
Zapp, Josef
Thevis, Mario
Bernhardt, Rita
Sprache: Englisch
Titel: The Journal of Steroid Biochemistry and Molecular Biology
Bandnummer: 212
Heft: 9
Verlag/Plattform: Elsevier
Erscheinungsjahr: 2021
DDC-Sachgruppe: 570 Biowissenschaften, Biologie
Dokumenttyp: Journalartikel / Zeitschriftenartikel
Abstract: The human microsomal cytochrome P450 enzyme CYP46A1 plays a crucial role in cholesterol elimination from the brain. It performs a 24-hydroxylation of cholesterol and is of outstanding significance for memory and cognition. This study demonstrates the catalytic activity of human CYP46A1 towards an anabolic androgenic steroid, oral turinabol (dehydrochloromethyltestosterone, 4-chloro-17β-dihydroxy,17α-methylandrosta-1,4-dien-3-one), which is a doping substance. CYP46A1 is the first human microsomal steroid-converting P450 showing activity towards this xenobiotic compound. Furthermore, the inhibitory effect of oral turinabol on the cholesterol conversion has been investigated in vitro demonstrating competition of the two substrates on the active site of CYP46A1 which might be of importance for potential pathogenic effects of oral turinabol. The conversion of oral turinabol was found to be selective resulting in the formation of only one product, as shown by HPLC analysis. To produce sufficient amounts of this product for NMR analysis, a system expressing human full-length CYP46A1 and CPR on a bicistronic vector was successfully developed realizing the selective cholesterol 24-hydroxylation in E. coli in mg amounts. Using this novel whole-cell system, the conversion of oral turinabol was performed and the product of this conversion by CYP46A1 was isolated and identified as 16β-hydroxy oral turinabol by NMR.
DOI der Erstveröffentlichung: 10.1016/j.jsbmb.2021.105927
URL der Erstveröffentlichung: https://www.sciencedirect.com/science/article/abs/pii/S0960076021001205
Link zu diesem Datensatz: urn:nbn:de:bsz:291--ds-400945
hdl:20.500.11880/36098
http://dx.doi.org/10.22028/D291-40094
ISSN: 0960-0760
Datum des Eintrags: 12-Jul-2023
Fakultät: NT - Naturwissenschaftlich- Technische Fakultät
Fachrichtung: NT - Biowissenschaften
NT - Pharmazie
Professur: NT - Prof. Dr. Volkhard Helms
NT - Prof. Dr. Alexandra K. Kiemer
Sammlung:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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