Peroxidase-dependent deactivation of prostacyclin synthetase.
A study of the enzymes of the arachidonic acid cascade revealed a high sensitivity of prostacyclin synthetase and a complete resistance of thromboxane A2 synthetase to time-dependent destruction by an oxidant [Ox] released during the peroxidase-catalyzed reduction of hydroperoxy fatty acids. The destructive action of [Ox] derived from prostaglandin G1 (PGG1), 15-hydroperoxy-PGE1, 15-hydroperoxy-5,8,11,13-eicosatetraenoic acid, and 12-hydroperoxy-5,8,10,14-eicosatetraenoic acid upon prostacyclin synthetase was prevented by 2-aminomethyl-4-t-butyl-6-iodophenol. On the other hand, deactivation resulting from PGG2 metabolism was neither time-dependent nor sensitive to 2-aminomethyl-4-t-butyl-6-iodophenol. The possibility that the action of [Ox] may alter the arachidonic acid cascade in favor of thromboxane A2 is discussed in view of its possible implications in inflammatory and other pathological processes.
D000818:Animals; D003577:Cytochrome P-450 Enzyme System; D011464:Epoprostenol / Q000096:biosynthesis*; D006168:Guinea Pigs; D019746:Intramolecular Oxidoreductases; D008168:Lung / Q000201:enzymology; D008297:Male; D008861:Microsomes / Q000201:enzymology; D010544:Peroxidases; D011453:Prostaglandins / Q000096:biosynthesis*; D012669:Seminal Vesicles / Q000201:enzymology; D012756:Sheep; D013928:Thromboxane A2; D013930:Thromboxane-A Synthase / Q000378:metabolism
D011453:Prostaglandins; D013928:Thromboxane A2; D003577:Cytochrome P-450 Enzyme System; D011464:Epoprostenol; D010544:Peroxidases; D019746:Intramolecular Oxidoreductases; C022461:prostacyclin synthetase; D013930:Thromboxane-A Synthase