Abstract
Oxygenation of the 5-lipoxygenase product 5 S-hydroxyeicosatetraenoic acid by cyclooxygenase-2 yields a bicyclic di-endoperoxide. The di-endoperoxide contains two peroxides spanning from carbons 9 to 11 and 8 to 12, and two hydroxyls at carbons 5 and 15 of arachidonic acid (Schneider C., et al. 2006. Convergent oxygenation of arachidonic acid by 5-lipoxygenase and cyclooxygenase-2. J. Am. Chem. Soc. 128: 720). Here, we report that treatment of the di-endoperoxide with hematin or ferrous chloride results in cleavage of both peroxide O-O bonds and of the bonds between the carbons that carry the peroxide groups, producing the aldehydes 4-hydroxy-2 E -nonenal (4-HNE), 8-oxo-5 S -hydroxy-6 E -octenoic acid, and malondialdehyde (MDA). The hematin- and ferrous iron-catalyzed transformation of the di-endoperoxide proceeded with a similar yield of products as the cleavage of the prostaglandin endoperoxide PGH2 to 12S-hydroxy-5Z,8E,10E-heptadecatrienoic acid and MDA. Chiral phase HPLC analysis of the 4-HNE cleavage product showed greater than 98% 4S and thus established the S confi guration of the 15-carbon of the di-endoperoxide that had not previously been assigned. This transformation of the 5-lipoxygenase/cyclooxygenase-2 derived di-endoperoxide invokes the possibility of a novel pathway to formation of the classic lipid peroxidation products 4-HNE and MDA.
Original language | English (US) |
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Pages (from-to) | 2455-2462 |
Number of pages | 8 |
Journal | Journal of lipid research |
Volume | 50 |
Issue number | 12 |
DOIs | |
State | Published - Dec 1 2009 |
Externally published | Yes |
Keywords
- 4-hydroxy-nonenal
- Aldehyde
- Lipid peroxide
- Malondialdehyde
- Prostaglandin
ASJC Scopus subject areas
- Biochemistry
- Endocrinology
- Cell Biology