Glutathione peroxidase is neither required nor kinetically competent for conversion of 5-HPETE to 5-HETE in rat PMN lysates.
In the 5-lipoxygenase pathway for arachidonic acid metabolism, reduction of 5-hydroperoxyeicosatetraenoic acid (5-HPETE) to 5-hydroxyeicosatetraenoic acid (5-HETE) is catalyzed by an activity different from glutathione peroxidase. Glutathione peroxidase here refers to the nonspecific peroxidase that catalyzes the reduction by glutathione of cumene hydroperoxide and a variety of other peroxides including 5-HPETE. This enzyme is inhibited by mercaptosuccinic acid. Preparations of the 15,000xg supernatant from lysed rat peritoneal polymorphonuclear leukocytes were the source of these activities. Thus, when glutathione peroxidase is inhibited to less than 0.5% of its normal activity by mercaptosuccinic acid, 5-HPETE is reduced as efficiently as in the absence of mercaptosuccinate. In lysate preparations from which endogenous glutathione has been removed, reduction of 5-HPETE is still observed but only in the presence of added reducing agents, e.g., 0.2 mM glutathione. When endogenous glutathione peroxidase is not inhibited, reduction of 5-HPETE occurs at a rate greater than 15-fold faster than can be accounted for by this activity. We conclude, therefore, that the glutathione peroxidase in rat PMNs is not kinetically competent to account for reduction of 5-HPETE. There is a distinct peroxidase that catalyzes this reaction. The 5-HPETE peroxidase can utilize glutathione as reducing agent but is not inhibited by mercaptosuccinate, and additional results indicate that it is inactivated during turnover.
D000818:Animals; D001091:Arachidonate Lipoxygenases; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000097:blood*; D002474:Cell-Free System; D005978:Glutathione / Q000097:blood; D005979:Glutathione Peroxidase / Q000037:antagonists & inhibitors / Q000097:blood*; D006893:Hydroxyeicosatetraenoic Acids / Q000097:blood*; D066298:In Vitro Techniques; D007700:Kinetics; D015289:Leukotrienes; D008084:Lipoxygenase / Q000097:blood; D009504:Neutrophils / Q000378:metabolism*; D010084:Oxidation-Reduction; D010544:Peroxidases / Q000097:blood; D051381:Rats; D013870:Thiomalates / Q000494:pharmacology
D001095:Arachidonic Acids; D006893:Hydroxyeicosatetraenoic Acids; D015289:Leukotrienes; D013870:Thiomalates; D016718:Arachidonic Acid; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; C025348:arachidonic acid 5-hydroperoxide; C046062:2-thiomalic acid; D010544:Peroxidases; C032991:arachidonic acid peroxide peroxidase; D005979:Glutathione Peroxidase; D001091:Arachidonate Lipoxygenases; D008084:Lipoxygenase; D005978:Glutathione