Cooperative interaction of dimeric enzyme prostaglandin H synthase with substrate – arachidonic acid

Krivoshey, A.; Barkhatov, V.; Efremov, A.; Matveishina, E.; Panova, V.; Vrzheshch, P.

Авторы: Krivoshey A., Barkhatov V., Efremov A., Matveishina E., Panova V., Vrzheshch P.
Журнал: FEBS open bio
Том: 11
Номер: S1
Год издания: 2021
Издательство: John Wiley & Sons Inc.
Местоположение издательства: United States
Первая страница: 326
Последняя страница: 326
DOI: 10.1002/2211-5463.13205
Аннотация: Prostaglandins are regulators of inflammation, immune response and many other physiological processes. Synthesis of prostaglandins is a result of cyclooxygenase oxidation of arachidonic acid (AA), which is catalyzed by homodimeric enzyme prostaglandin H synthase (PGHS). PGHS is irreversibly inactivated during catalyzed reaction and inhibited by nonsteroidal anti-inflammatory drugs (NSAIDs). There was some evidence of cooperative interactions between enzyme subunits, but cooperativity of AA binding to the active sites was not investigated sufficiently. In this study, we used the PGHS-1 isoform purified from sheep vesicular glands. The cyclooxygenase reaction was detected amperometrically from the consumption of dissolved molecular oxygen. Obtained data were analyzed using Origin and MATLAB. It was shown that the dependence of cyclooxygenase oxidation rate in the wide range of AA concentrations is not described by Michaelis-Menten equation. However, it can be described by model taking into account the negative cooperativity of AA binding to PGHS subunits (the enzyme affinity to the first AA molecule is 14 μM, and the affinity to the second AA molecule is 1 mM). The investigations of integral kinetics of cyclooxygenase reactiondemonstrated that total enzyme turnover number (from the beginning of the reaction until complete inactivation) decreases with the increase of AA concentration. The experimental dependences were described by cooperative model, and the values of kinetic constants were found. Obtained results should be takeninto account during the investigation of prostaglandin synthesis and pharmacological effects of NSAIDs in vivo.
Добавил в систему: Кривошей Александр Владимирович

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