Flavin-containing monooxygenase 1-catalysed N,N-dimethylamphetamine N-oxidation

Title
Flavin-containing monooxygenase 1-catalysed N,N-dimethylamphetamine N-oxidation
Authors
이상규강민정진창배인문교김동현유혜현
Keywords
FMO; N,N-dimethylamphetamine (DMA); N-oxidation; avin-containing monooxygenase; N,N-dimethylamphetamine N-oxide (DMANO)
Issue Date
2009-09
Publisher
Xenobiotica
Citation
VOL 39, NO 9, 680-686
Abstract
N,N-dimethylamphetamine (DMA) is a methamphetamine analogue known to be a weaker central nerv- ous system stimulant than methamphetamine. Although a major metabolite of DMA is known to be DMA N-oxide (DMANO), which may be catalysed by avin-containing monooxygenase (FMO), the speci c enzyme(s) involved in this biotransformation has not been identi ed. In this study, the speci c enzyme(s) involved with DMA N-oxidation was characterized by several assays. When DMA was incubated with di er- ent human recombinant drug-metabolizing enzymes, including FMOs and cytochrome P450s (CYPs), the formation of DMANO by FMO1 was the most predominant. The Michaelis–Menten kinetic constants for DMA N-oxidation by FMO1 were: Km of 44.5 μM, Vmax of 7.59 nmol min−1 mg−1 protein, and intrinsic clear- ance of 171 μl min−1 mg−1 protein, which was about twelve-fold higher than that by FMO3. Imipramine, an FMO1-speci c inhibitor, selectively inhibited DMA N-oxidation. The resulting data showed that DMA N-oxidation is mainly mediated by FMO1.
URI
http://pubs.kist.re.kr/handle/201004/45529
ISSN
0049-8254
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KIST Publication > Article
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