Kinetic Isotope Effect of Prostaglandin H Synthase Exhibits Inverted Temperature Dependence

Autor: Gang Wu, Richard J. Kulmacz, Ah-Lim Tsai
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Zdroj: Catalysts, Vol 4, Iss 2, Pp 174-185 (2014)
Druh dokumentu: article
ISSN: 2073-4344
DOI: 10.3390/catal4020174
Popis: Conversion of arachidonic acid to prostaglandin G2/H2 catalyzed by prostaglandin H synthase (PGHS) is proposed to involve initial transfer of the C13 pro-(S) hydrogen atom from arachidonate to the Tyr385 radical in PGHS, followed by insertion of two oxygen molecules and several chemical bond rearrangements. The initial hydrogen-transfer was recently concluded to be a rate-limiting step in cyclooxygenase catalysis based on the observed intrinsic deuterium kinetic isotope effect values (Dkcat). In the present study, we have found that Dkcat values of both PGHS-1 and -2 show an unusual increase with temperatures in the range of 288–310 K, exhibiting an inverted temperature dependence. The value of lnDkcat, however, decreased linearly with 1/T, consistent with a typical Arrhenius relationship.
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