Autoxidative transformation of chiral omega6 hydroxy linoleic and arachidonic acids to chiral 4-hydroxy-2E-nonenal.

Schneider C, Porter NA, Brash AR
Chem Res Toxicol. 2004 17 (7): 937-41

PMID: 15257619 · DOI:10.1021/tx049913n

Recently, we established that 13S-hydroperoxy-linoleic acid is converted to 4S-hydroperoxy-nonenal (4S-HPNE) during autoxidation, implicating hydrogen abstraction from C-8 as an initiating step [Schneider, C., et al. (2001) J. Biol. Chem. 275, 20831-20838]. On the basis of the proposed mechanism, an equivalent initiating reaction could occur from the corresponding 13S-hydroxy acid. Herein, we examined the outcome of autoxidation reactions of the omega6 hydroxy fatty acids, 13S-hydroxyoctadecadienoic acid and 15S-hydroxyeicosatetraenoic acid, as compared with reactions of the corresponding hydroperoxy substrates. Autoxidation of the hydroxy starting materials (37 degrees C, dry film) yielded 4-hydroxy-nonenal (4-HNE) as a prominent polar metabolite (and not the 4-hydroperoxide), whereas the hydroperoxide starting materials gave rise to 4-HPNE. Stereochemical analysis showed that the optical purity of the 4-hydroxy group of 4-HNE precisely matched the optical purity of the 15S- or 13S-hydroxy group of the starting fatty acid substrate (98 and 90% S, respectively). The hydroperoxide 15S-HPETE (98% 15S) gave rise to 4S-HPNE, also with retention of optical purity (98% 4S). The preservation of stereochemical configuration provides evidence that aldehyde formation does not involve participation of the hydro(pero)xy group and indicates a similar mechanism for the formation of 4-HNE and 4-HPNE during autoxidation of omega6 hydro(pero)xy fatty acids. Our results establish, moreover, that omega6 hydroxy fatty acids are potential precursors of reactive cytotoxic aldehydes in biological systems.

MeSH Terms (6)

Aldehydes Arachidonic Acid Eicosanoic Acids Linoleic Acids Oxidation-Reduction Stereoisomerism

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