ИСТИНА

Dimeric enzyme prostaglandin H synthase (PGHS), also known as cyclooxygenase (COX), is the key enzyme responsible for prostaglandin biosynthesis in mammals. PGHS is a main target of non-steroid anti-inflammatory drugs (NSAIDs). We have analyzed how does velocity and yield of cyclooxygenase reaction depend on concentration of major PGHS substrate – arachidonic acid (AA). We have shown that the velocity of the reaction and its’ integral kinetics (the dependence of product concentration on time) do not follow Michaelis-Menten model at a wide range of AA concentration (from 0 to 2000 µM). Rather, the data obtained can be described by the theoretical model that takes into account cooperative interactions between two PGHS subunits. We have demonstrated the phenomena of negative cooperativity, where affinity to AA of the first subunit declines upon AA binding by the second subunit. Moreover, the affinity of the subunit to AA changes upon inactivation of another subunit during the reaction. We have defined kinetics parameters of the cooperative scheme described above. The results of our work may have significant importance for investigations of prostaglandin biosynthesis and pharmacological effects of NSAIDs in vivo.