title: Fragmentation of a linoleate-derived γ-hydroperoxy-α,β-unsaturated epoxide to γ-hydroxy- and γ-oxo-alkenals involves a unique pseudo-symmetrical diepoxycarbinyl radical.
abstract: Many of the pathological effects of lipid peroxidation are mediated by aldehydes generated through fragmentation of lipid peroxides. Among these aldehydes, the γ-hydroxy- and γ-oxo-α,β-alkenals, e.g., 4-hydroxy-2-nonenal (HNE) and 4-oxo-2-nonenal (ONE), are especially prone to modifying proteins and DNA through covalent adduction. In addition the "mirror image" γ-hydroxy- and γ-oxo-α,β-alkenal phospholipids can serve as high-affinity ligands for biological receptors triggering pathology. Therefore, the mechanisms by which these aldehydes are generated in vivo are under intense scrutiny. We now report observations supporting the intermediacy of a unique pseudo-symmetrical diepoxycarbinyl radical that accounts for the coproduction of HNE, ONE, and their mirror image analogues 9-hydroxy-12-oxo-10(E)-dodecenoic acid and 9-keto-12-oxo-10-dodecenoic acid upon fragmentation of 13-hydroperoxy-cis-9,10-epoxyoctadeca-11-enoic acid.
authors.affiliation: Department of Chemistry, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Gu
authors.affiliation: Department of Chemistry, Case Western Reserve University, Cleveland, OH 44106, USA. Electronic address: rgs@case.edu.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Salomon
mesh_terms: D000447:Aldehydes / Q000737:chemistry; D004852:Epoxy Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D005609:Free Radicals / Q000737:chemistry*; D006868:Hydrolysis; D007501:Iron / Q000737:chemistry; D008041:Linoleic Acids / Q000138:chemical synthesis / Q000737:chemistry*; D015227:Lipid Peroxidation; D010084:Oxidation-Reduction; D053719:Tandem Mass Spectrometry
chemical_list: C403894:4-oxo-2-nonenal; D000447:Aldehydes; D004852:Epoxy Compounds; D005609:Free Radicals; D008041:Linoleic Acids; D007501:Iron; C027576:4-hydroxy-2-nonenal