title: New insights regarding the autoxidation of polyunsaturated fatty acids.
abstract: Free radical-initiated autoxidation of polyunsaturated fatty acids (PUFAs) has been implicated in numerous human diseases, including atherosclerosis and cancer. This review covers the free radical mechanisms of lipid oxidation and recent developments of analytical techniques to analyze the lipid oxidation products. Autoxidation of PUFAs generates hydroperoxides as primary oxidation products, and further oxidation leads to cyclic peroxides as secondary oxidation products. Characterization of these oxidation products is accomplished by several mass spectrometric techniques. Ag+ coordination ion spray mass spectrometry has proven to be a powerful tool to analyze the intact lipid peroxides. Monocyclic peroxides, bicyclic endoperoxides, serial cyclic peroxides, and a novel class of endoperoxides (dioxolane-isoprostane peroxides) have been identified from the oxidation of arachidonate. Electron capture atmospheric pressure chemical ionization mass spectrometry has been applied to study lipid oxidation products after derivatization. All eight possible diastereomeric isoprostanes are observed from the oxidation of a single hydroperoxide precursor. 5- and 15-series isoprostanes are more abundant than the 8- and 12-series because the precursors that lead to 8- and 12-series compounds can undergo further oxidation and form dioxolane-isoprostane peroxides. Furthermore, formation of isoprostanes from 15-hydroperoxyeicosatetraenoate occurs from beta-fragmentation of the corresponding peroxyl radical to generate a pentadienyl radical rather than a "dioxetane" intermediate, as previously suggested.
authors.affiliation: Departments of Chemistry and Pharmacology, Center in Molecular Toxicology, Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, TN 37235, USA.
authors.forename: Huiyong
authors.initials: H
authors.lastname: Yin
authors.forename: Ned A
authors.initials: NA
authors.lastname: Porter
mesh_terms: D000818:Animals; D001161:Arteriosclerosis / Q000473:pathology; D004583:Electrons; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D005609:Free Radicals; D006801:Humans; D028421:Isoprostanes / Q000737:chemistry; D015289:Leukotrienes / Q000737:chemistry; D015227:Lipid Peroxidation; D008054:Lipid Peroxides / Q000737:chemistry; D008055:Lipids / Q000737:chemistry; D013058:Mass Spectrometry; D008956:Models, Chemical; D009369:Neoplasms / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D010545:Peroxides / Q000737:chemistry; D012834:Silver / Q000494:pharmacology; D021241:Spectrometry, Mass, Electrospray Ionization; D013997:Time Factors
chemical_list: D005231:Fatty Acids, Unsaturated; D005609:Free Radicals; D028421:Isoprostanes; D015289:Leukotrienes; D008054:Lipid Peroxides; D008055:Lipids; D010545:Peroxides; D012834:Silver; C025086:15-hydroperoxy-5,8,11,13-eicosatetraenoic acid; D010100:Oxygen