An in vitro study of enhanced H+ diffusion by urease action on urea. Implications for Helicobacter pylori-associated peptic ulceration.
The in vitro effect of urea and hydrolysis of urea by urease on mucus H+ permeability is reported here. The effective DHCl values indicate a strong pH dependence for H+ diffusion in both water and mucus layers, with no apparent trend at concentrations between 1 and 50 mM urea. However, the estimated DHCl at near-neutral and alkaline pH are 4- to 10-fold lower through mucus than through aqueous films. Moreover, the pKa values of HCO3- and NH3 (generated by urease action on urea) had a profound effect on measured DHCl. These in vitro studies suggest that a high local concentration of NH3 and HCO3- within the mucus layer, generated by the action of Helicobacter pylori urease on endogenous intragastric urea, could greatly accelerate proton flux to the surface epithelium by operation of a buffer shuttle. This results in enhanced H+ permeability, particularly at pKa values of HCO3- and NH3, and in extreme circumstances it may result in gastric ulcer formation.
Desai
M A
MA
Dept. of Medicine (Clinical Biochemistry), University of Manchester, Hope Hospital, Salford, UK.
Vadgama
P M
PM
D000818:Animals; D004058:Diffusion; D005756:Gastritis / Q000378:metabolism* / Q000382:microbiology; D016481:Helicobacter Infections / Q000150:complications; D016480:Helicobacter pylori; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D066298:In Vitro Techniques; D008954:Models, Biological; D009093:Mucus / Q000378:metabolism*; D010437:Peptic Ulcer / Q000378:metabolism* / Q000382:microbiology; D010539:Permeability; D013552:Swine; D014508:Urea / Q000378:metabolism*; D014510:Urease / Q000493:pharmacokinetics*; D014867:Water / Q000378:metabolism
D014867:Water; D014508:Urea; D014510:Urease