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Keywords = temperature dependence of KIE

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12 pages, 2000 KB  
Communication
Kinetic Isotope Effect of Prostaglandin H Synthase Exhibits Inverted Temperature Dependence
by Gang Wu, Richard J. Kulmacz and Ah-Lim Tsai
Catalysts 2014, 4(2), 174-185; https://doi.org/10.3390/catal4020174 - 11 Jun 2014
Cited by 3 | Viewed by 6606
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Enzymes in Organic Synthesis)
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