文章基本信息

标题：Kinectic Studies of Helicobacter pylori Urease Inhibition by a Novel Proton Pump Inhibitor, Rabeprazole
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作者：JongBeak PARK ; Lisa IMAMURA ; Kyoichi KOBASHI 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：1996
卷号：19
期号：2
页码：182-187
DOI：10.1248/bpb.19.182
出版社：The Pharmaceutical Society of Japan
摘要：Urease is an important virulence factor of pathogenicity of gastric Helicobacter pylori. The inhibition of H. pylori urease by the novel proton pump inhibitor, rabeprazole, was investigated kinetically. It was found to act as an irreversible noncompetitive inhibitor of the enzyme. The inhibitory potency of rabeprazole was dependent on the pH of reaction mixture and its K_i values were 0.14μM (pH 5.0), 0.34μM (pH 7.0) and 6.10μM (pH 8.5). Progressive inactivation of urease by rabeprazole initially proceeded according to pseudo-first-order kinetics with respect to the remaining enzymatic activity at pH 7.0 and 37°C, with a second-order rate constant of 0.0017μM^-1 s^-1. When the inactivation half-life was plotted versus the reciprocal of the rabeprazole concentration, a straight line was obtained with a slope of -3.12. From an Arrhenius-plot of the temperature-dependence of the inactivation (over the range of 5-37°C), an activation energy of 13.2 kcal/mol was calculated. Recovery of activity was incomplete for H. pylori urease inhibited by rabeprazole, suggesting that the rabeprazole-urease complex is very stable.
关键词：Helicobacter pylori;rabeprazole;proton pump inhibitor;kinetic study;urease