15-hydroxy-5-8-11-13-eicosatetraenoic-acid and zileuton

15-hydroxy-5-8-11-13-eicosatetraenoic-acid has been researched along with zileuton* in 1 studies

Other Studies

1 other study(ies) available for 15-hydroxy-5-8-11-13-eicosatetraenoic-acid and zileuton

ArticleYear
Eosinophil 15-lipoxygenase is a leukotriene A4 synthase.
    The Journal of biological chemistry, 1994, Oct-28, Volume: 269, Issue:43

    5-Lipoxygenase is the first committed enzyme in the leukotriene biosynthetic pathway and is known to catalyze not only the first oxygenation of arachidonate to form 5(S)-hydroperoxyeicosatetraenoic acid (5(S)-HPETE), but also dehydration of this intermediate into leukotriene A4 (LTA4) by an activity termed leukotriene A4 synthase. Inhibition of cytosolic 5-lipoxygenase prepared from human blood granulocytes with zileuton (100 microM) was virtually complete, but LTA4 synthase activity was only inhibited by 47%. Structural characterization of eicosanoids synthesized in these preparations revealed an abundance of 15-lipoxygenase metabolites including 15-HETE when arachidonate was used as substrate and 5(S),15(S)-dihydroxy-6,8,11,13(E,E,Z,Z)-eicosatetraenoic acid when 5(S)-HPETE was used as substrate. When neutrophils were prepared that contained less than 1% eosinophil contamination, zileuton was found to almost completely inhibit all 5-lipoxygenase, as well as LTA4 synthase products. Immunochemical analysis of the supernatants from purified neutrophils and eosinophils confirmed the previous observation that neutrophils do not express 15-lipoxygenase. Incubation of 5(S)-HPETE with recombinant mammalian 15-lipoxygenase resulted in the formation of 6-trans-LTB4 and 6-trans-12-epi-LTB4 as LTA4 products, as well as the 12-lipoxygenase product 5(S),12(S)-diHPETE. The mechanism of action of 15-lipoxygenase acting as an LTA4 synthase is proposed to involve removing the pro-R hydrogen atom at carbon-10 of 5(S)-HPETE, which is antarafacial to the hydroperoxy group to yield LTA4.

    Topics: Arachidonate 15-Lipoxygenase; Arachidonate 5-Lipoxygenase; Arachidonic Acid; Cell-Free System; Cytosol; Dose-Response Relationship, Drug; Eosinophils; Granulocytes; Humans; Hydroxyeicosatetraenoic Acids; Hydroxyurea; Leukotriene A4; Leukotrienes; Lipoxygenase Inhibitors; Models, Chemical; Neutrophils; Recombinant Proteins

1994