Autoxidative transformation of chiral omega6 hydroxy linoleic and arachidonic acids to chiral 4-hydroxy-2E-nonenal.
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.
Schneider
Claus
C
Department of Pharmacology, Vanderbilt University Medical School, Nashville, Tennessee 37232, USA.
Porter
Ned A
NA
Brash
Alan R
AR
D000447:Aldehydes / Q000737:chemistry*; D016718:Arachidonic Acid / Q000737:chemistry*; D004537:Eicosanoic Acids / Q000737:chemistry*; D008041:Linoleic Acids / Q000737:chemistry*; D010084:Oxidation-Reduction; D013237:Stereoisomerism
D000447:Aldehydes; D004537:Eicosanoic Acids; D008041:Linoleic Acids; D016718:Arachidonic Acid; C024348:13-hydroxy-9,11-octadecadienoic acid; C073049:15-hydroxyeicosanoic acid; C027576:4-hydroxy-2-nonenal