Asymmetric metabolicN-oxidation ofN-ethyl-N-methylaniline by purified flavin-containing monooxygenase
| Autor: | Andrew J. Hutt, Mark R. Hadley, Harriet G. Oldham, L. A. Damani |
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| Rok vydání: | 1994 |
| Předmět: |
Tertiary amine
Swine Stereochemistry Metabolite Flavin-containing monooxygenase In Vitro Techniques Catalysis Analytical Chemistry chemistry.chemical_compound Cytochrome P-450 Enzyme System Drug Discovery Animals Biotransformation Chromatography High Pressure Liquid Spectroscopy Pharmacology chemistry.chemical_classification Aniline Compounds Organic Chemistry Substrate (chemistry) Stereoisomerism Free Radical Scavengers Hydrogen-Ion Concentration Monooxygenase Enzyme Activation Enzyme Liver chemistry Oxygenases Microsome Cattle Spectrophotometry Ultraviolet Stereoselectivity Oxidation-Reduction |
| Zdroj: | Chirality. 6:98-104 |
| ISSN: | 1520-636X 0899-0042 |
| DOI: | 10.1002/chir.530060210 |
| Popis: | The prochiral tertiary amine N-ethyl-N-methylaniline (EMA) is known to be metabolically N-oxygenated in vitro with microsomal preparations. This biotransformation is thought to be mediated predominantly by the flavin-containing monooxygenase (FMO) enzyme system. Microsomal N-oxygenation of EMA is known to be stereoselective and varies between species. In order to further characterise this metabolic transformation, we have examined the in vitro metabolism of EMA using purified porcine hepatic FMO. Following incubation of EMA with purified FMO, EMA N-oxide, the only metabolite detected, was found to be produced stereoselectively [ratio (−)-(S):(+)-(R), ca. 4:1]. The enantiomeric ratio of the N-oxide product did not change markedly with respect to time, enzyme or substrate concentration. Determination of the kinetics of formation of the N-oxide indicated a single affinity for the prochiral substrate with differential rates of formation of the enantiomers. The extent of EMA N-oxide formation was shown to be affected by activators and inhibitors of FMO and pH, but its stereoselectively was unaltered. © 1994 Wiley-Liss, Inc. |
| Databáze: | OpenAIRE |
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