New players in the nightwatch research

Maria Kristina Parr, A. Zöllner, Gregor Fußhöller, G. Opfermann, A. Hobler, R. Bernhardt, M. Bureik, Wilhelm Schänzer

Publication: Chapter in Book/Report/Conference proceedingConference contribution - Article for conferenceResearch

Abstract

The metabolism of a variety anabolic steroids frequently misused for doping purposes has been investigated in the last years. This research mainly focused on main and long-term metabolites suitable for detection, but detailed clearance mechanisms have rarely been elucidated. Recent studies on metandienone focused on the identification of 17β-hydroxy-methyl—17α-methyl-18-norandrosta—1,4,13—trien—3—one (NV) as long—term metabolite. It was introduced to the community as “nightwatch’ (NV) by Schänzer et al. in 2006. The metabolic pathway of its generation, however, remained unclear. In-vitro experiments using Metandienone and its Wagner-Meerwein rearrangement product 17,17-dimethyl-18-norandrosta-1,4,13-trien-3-one (NorMD) using different human cytochrome P450 enzymes (CYPs) resulted in hydroxylations of the substrates. Biotechnological synthesis was performed by hydroxylation of NorMD.NV was obtained using recombinant strains of the fission yeast Schizosaccharomices pombe expressing the human cytochrome P450 enzyme CYP21. Also CYP3A4 was shown to catalyze this reaction (Zöllner et al., 2010). Herein, we report the hydroxylation of metandienone itself using the purified human cytochrome P450 enzymes CYP11B1 and CYP11B2. Both enzymes are known to catalyze β-hydroxylations at C-11. Additionally, CYP11B2, also named aldosterone synthase, is known to perform C-18 hydroxylations. Verf.-Referat
Original languageGerman
Title of host publicationRecent advances in doping analysis (19) : Proceedings of the Manfred-Donike-Workshop, 29th Cologne Workshop on Dope Analysis : 13th to 18th February 2011
EditorsWilhelm Schänzer, Hans Geyer, A. Gotzmann, Ute Mareck
Number of pages3
PublisherSportverlag Strauß
Publication date2011
Pages60-62
Publication statusPublished - 2011
EventCologne Workshop on Dope Analysis - Köln, Germany
Duration: 13.02.201118.02.2011
Conference number: 29

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