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

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 modify 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-dodec-10-enoic acid (HODA), 9-keto-12-oxo-dodec-10-enoic acid (KODA) upon fragmentation of 13-hydroperoxy-cis-9,10-epoxyoctadeca-11-enoic acid (13-HP-Epo-Acid).