Prostaglandin endoperoxide synthetase from bovine vesicular gland microsomes. Inactivation and activation by heme and other metalloporphyrins.
Prostaglandin endoperoxide synthetase purified to apparent homogeneity from bovine vesicular gland microsomes contained iron far below the equimolar amount and essentially no heme. However, the enzyme required various metalloporphyrins including hematin or several hemoproteins such as hemoglobin. Preincubation of the enzyme with hematin or hemoglobin resulted in the loss of enzyme activity. The enzyme inactivation was protected by tryptophan or various other aromatic compounds. Furthermore, the simultaneous presence of tryptophan brought about activation of enzyme; namely, the enzyme preincubated with heme and tryptophan showed an almost full activity with a heme concentration in the reaction mixture far below the saturating level. Such inactivation and activation of the enzyme were also observed with manganese protoporphyrin. An identical heme requirement, heme-induced inactivation, and activation of the enzyme were observed in three types of reactions catalyzed by the enzyme: 1) bis-dioxygenation of 8,11,14-eicosatrienoic acid to produce prostaglandin G1, 2) 15-hydroperoxide cleavage of prostaglandin G1 to produce prostaglandin H1, and 3) guaiacol peroxidation. When heme was replaced by manganese protoporphyrin, the enzyme catalyzed only the bis-dioxygenation producing prostaglandin G1 and the activities of the latter two reactions were not detectable.
D000818:Animals; D002417:Cattle; D004789:Enzyme Activation; D006418:Heme / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D008665:Metalloporphyrins / Q000494:pharmacology*; D008861:Microsomes / Q000201:enzymology*; D011449:Prostaglandin Endoperoxides; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D012669:Seminal Vesicles / Q000201:enzymology*; D013329:Structure-Activity Relationship
D008665:Metalloporphyrins; D011449:Prostaglandin Endoperoxides; D006418:Heme; D011451:Prostaglandin-Endoperoxide Synthases