Lipoxygenation activity of purified prostaglandin-forming cyclooxygenase.
Purified cyclooxygenase, a single enzyme which catalyzes the formation of endoperoxide from arachidonic acid (20:4) in a bis(dioxygenase) reaction, is capable of oxygenating eicosadienoic acid (20:2) at C-11 in a single dioxygenase reaction. The partial oxygenation of 20:2 resembles the formation of prostaglandin from 20:4, with both oxygenation reactions exhibiting similar pH optima, substrate Km values, and cofactor effects including a need for peroxide and an absolute requirement for heme. In addition, those processes known to destroy 20:4 oxygenase activity, such as heat inactivation, inactivation with anti-inflammatory drugs, and turnover-mediated inactivation, have equally destructive effects on 20:2 oxygenase activity. Thus, both oxygenations are catalyzed by one enzyme. All of the above similarities for 20:2 and 20:4 oxygenation demonstrate that C-11 oxygenation is an integral rate-limiting step of cyclooxygenase action rather than a separate reaction resembling that of plant lipoxygenase.
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D006418:Heme / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D008297:Male; D010545:Peroxides / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000302:isolation & purification / Q000378:metabolism*; D012669:Seminal Vesicles / Q000201:enzymology*; D012756:Sheep
D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D005231:Fatty Acids, Unsaturated; D010545:Peroxides; D006418:Heme; D011451:Prostaglandin-Endoperoxide Synthases