title: N-Oxidation of 4-chloroaniline by prostaglandin synthase. Redox cycling of radical intermediate(s).
abstract: 4-Chloroaniline undergoes N-oxidation in ram seminal-vesicle microsomal preparations supplemented with arachidonic acid to yield N-(4-chlorophenyl)-hydroxylamine and 1-chloro-4-nitrosobenzene. H2O2 also supports metabolism of the amine substrate to the same organic-solvent-extractable products, suggesting that the hydroperoxidase activity of prostaglandin synthase is responsible for the co-oxidation. Analysis of the reaction mixtures by e.s.r. spectrometry reveals the formation of a radical intermediate bearing the characteristics of a strongly immobilized nitroxide. Arylamine-stimulated O2.- release can be observed when the arachidonic acid-containing incubation media are supplemented with NADPH. Redox cycling of the nitroxide/hydroxylamine couple is presumed to represent the major source of O2.-, but additional mechanisms, such as redox changes of nitro anion radicals resulting from potential further metabolism of 1-chloro-4-nitrosobenzene, cannot be excluded. The concerted action of carrier-bound nitroxides and O2.- in initiating damage of cellular macromolecules is discussed.
authors.forename: I
authors.initials: I
authors.lastname: Golly
authors.forename: P
authors.initials: P
authors.lastname: Hlavica
mesh_terms: D000814:Aniline Compounds / Q000378:metabolism*; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D066298:In Vitro Techniques; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D009249:NADP / Q000494:pharmacology; D010084:Oxidation-Reduction; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D012669:Seminal Vesicles / Q000378:metabolism; D012756:Sheep; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
chemical_list: D000814:Aniline Compounds; D001095:Arachidonic Acids; D005609:Free Radicals; D013481:Superoxides; D016718:Arachidonic Acid; D009249:NADP; D011451:Prostaglandin-Endoperoxide Synthases; D013482:Superoxide Dismutase; C004658:4-chloroaniline