Mechanism for irreversible self-deactivation of prostaglandin synthetase.

摘要: It has been shown that prostaglandin (PG) cyclooxygenase is irreversibly self-deactivated during the oxygenation of arachidonic acid (Smith, W. L., and Lands, W.E.M. (1972) Biochemistry II, 3273-3285). Using several experimental approaches an enzyme preparation which was highly active without artificial stimulation, we have extensively investigated mechanism this deactivation process. During generation PGH2 from acid, oxidizing equivalents were released reductive breakdown PGG2 found to deactivate cyclooxygenase. The cyclooxygenase-catalyzed metabolism both generated radicals scavenged by phenol. Both phenol methional (scavengers oxygen-centered radicals) promoted formation at expense increased initial rate extent reaction prior Hence, it appears due its oxidation formed as a result hydroperoxide on PGG2. Some experiments with dithiothereitol N-ethylmaleimide suggested may contain disulfide site. A devised accounts for self-deactivation phenomenon, effect methional, site, pathway substrate oxygenation.