Synthesis of 5-oxo-6,8,11,14-eicosatetraenoic acid and identification of novel omega-oxidized metabolites in the mouse macrophage
| Autor: | J M, Hevko, R C, Bowers, R C, Murphy |
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| Rok vydání: | 2001 |
| Předmět: |
Mice
Inbred ICR Spectrometry Mass Electrospray Ionization Macrophages Arachidonic Acids Cell Separation Catalysis Gas Chromatography-Mass Spectrometry Mice Cytosol Hydroxyeicosatetraenoic Acids Animals Calcium Spectrophotometry Ultraviolet Oxidation-Reduction Biotransformation Chromatography High Pressure Liquid Hydrogen |
| Zdroj: | The Journal of pharmacology and experimental therapeutics. 296(2) |
| ISSN: | 0022-3565 |
| Popis: | The metabolism of arachidonic acid by the 5-lipoxygenase pathway not only leads to the formation of leukotrienes but also to the biologically active eicosanoid 5-oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE). The synthesis of 5-oxo-ETE was investigated in the elicited peritoneal macrophage and the formation of 5-hydroxyeicosatetraenoic acid (5-HETE) as well as 5-oxo-ETE was quantitated using stable isotope dilution tandem mass spectrometry. The metabolism of 5-oxo-ETE in these same cells led to the formation of a series of novel less lipophilic metabolites oxidized near the methyl terminus that were structurally characterized using electrospray LC/MS and LC/MS/MS. Five novel metabolites of 5-oxo-ETE were identified including 5,18-diHETE, 5,19-diHETE, 5-oxo-19-HETrE, 5-oxo-18-HETrE, and 5,19-diHETrE. These metabolites corresponded to omega-1 and omega-2 oxidation of 5-oxo-ETE presumably formed by a specific cytochrome P450. There was no evidence for the formation of omega-oxidation (20-hydroxy metabolites), which are known products of metabolism of 5-oxo-ETE in other cell types. None of the metabolites were found to elevate intracellular calcium release, suggesting that this metabolic pathway may result in inactivation of 5-oxo-ETE. This is the first report of the biosynthesis of 5-oxo-ETE by tissue resident cell outside of the blood and the formation of novel omega-1 and omega-2 oxidation of this eicosanoid. |
| Databáze: | OpenAIRE |
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