Kinetic Isotope Effect of Prostaglandin H Synthase Exhibits Inverted Temperature Dependence

Catalysts

Gang Wu¹  Richard J. Kulmacz² 

[1] Department of Internal Medicine, University of Texas Medical School at Houston, 6431 Fannin St., Houston, TX 77030, USA;

关键词: prostaglandin H synthase-1 and -2;    deuterium kinetic isotope effect;    temperature dependence of KIE;   

DOI  :  10.3390/catal4020174

来源: mdpi

【 摘 要 】

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 (^Dk_cat). In the present study, we have found that ^Dk_cat 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 ln^Dk_cat, however, decreased linearly with 1/T, consistent with a typical Arrhenius relationship.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.