title: Kinetic studies of Helicobacter pylori urease inhibition by a novel proton pump inhibitor, rabeprazole.
abstract: 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 Ki values were 0.14 microM (pH 5.0), 0.34 microM (pH 7.0) and 6.10 microM (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 degrees C, with a second-order rate constant of 0.0017 microM-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 degrees 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.
authors.affiliation: Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Japan.
authors.forename: J B
authors.initials: JB
authors.lastname: Park
authors.forename: L
authors.initials: L
authors.lastname: Imamura
authors.forename: K
authors.initials: K
authors.lastname: Kobashi
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D001562:Benzimidazoles / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D016480:Helicobacter pylori / Q000201:enzymology*; D007700:Kinetics; D009853:Omeprazole / Q000031:analogs & derivatives; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors*; D064750:Rabeprazole; D014510:Urease / Q000037:antagonists & inhibitors*
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D001562:Benzimidazoles; D004791:Enzyme Inhibitors; D064750:Rabeprazole; D014510:Urease; D006180:Proton-Translocating ATPases; D009853:Omeprazole