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. 2012 Feb 1;52(3):601-606.
doi: 10.1016/j.freeradbiomed.2011.11.013. Epub 2011 Dec 1.

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

Xiaodong Gu  1 , Robert G Salomon  2
Affiliations

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

Xiaodong Gu et al. Free Radic Biol Med. .

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.

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Figures

Figure 1
Figure 1
Proposed mechanisms for the generation of HNE (9) and ONE (10) from arachidonate or linoleate hydroperoxides (1).
Figure 2
Figure 2
Proposed multiple fragmentations of 13-HP-Epo-Acid (11).
Figure 3
Figure 3
Epoxide C-O bond cleavage is kinetically favored over C-C bond cleavage for epoxycarbinyl radicals.
Figure 4
Figure 4
HPLC chromatogram of ONE (10), HNE (9), ON (12), and hexanal-DNPH derivatives. All chromatograms were monitored by LC/MS/MS in the negative ion mode with MRM of appropriate mass transitions as noted.
Figure 5
Figure 5
Generation of hexanal, ON (12), ONE (10), KODA (14), HNE (9) and HODA (13) from 13-HP-Epo-Acid (11) in the presence various amounts of Fe2+.
Figure 6
Figure 6
HPLC chromatogram of the HODA methoxime derivative (left) and KODA methoxime derivative (right). All chromatograms were monitored by LC/MS in the negative mode with the MRM of appropriate mass transitions as noted. The HODA and KODA methoxime derivatives were detected among the 13-HP-Epo-Acid (11) fragmentation reaction products.
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