Gastric mucosa, urease

Infection by H. pylori is detected by serological markers produced by host immune responses (e.g., antibodies to antigens of H. pylori) and a breath test. The latter, known as the urea breath test, consists of oral administrations of radioactively labeled urea. This is metabolized to labeled CO2 and ammonia by the urease of H. pylori present in the gastric mucosa. The presence of labeled CO2 measured in the exhaled air confirms infection. 

Takeuchi K, Ohuchi T, Harada H, et al. 1995. Irritant and protective action of urea-urease ammonia in rat gastric mucosa. Dig Dis Sci 40(2) 274-281. 

E. J. Conway, the indomitable Dublin biochemist, believed to the end that he had demonstrated that gastric urea is indeed present within the cytoplasm of cells of the gastric mucosa,and Oliver FitzGerald, Conway s clinical colleague, believed that because hydrolysis of a molecule of urea produces two hydroxyl ions, the function of gastric urease is to protect the mucosa by providing those ions to neutralize acid. 

Urease catalyzes the hydrolysis of urea to yield carbon dioxide and ammonia. Urease activity is common in higher plants, bacteria, and molds but is of limited distribution in animals. In no case has ureolytic activity been reported in the liver of vertebrates, although urea may be hydrolyzed by gastric mucosa and erythrocytes. Since urease was the first enzyme to be isolated in crystalline form, it has been the object of considerable study. 

The urease produced by Helicobacter spp. is a neutral pH optimum enzyme [12] therefore, a fall of cytoplasmic pH is not an adaptive mechanism for this organism. The inhabitation of the gastric mucosa by Helicobacter such as H. pylori requires specialization of properties of this micro-aerophilic bacterial species in order to enable survival and growth on the gastric surface and within antral glands. It should be noted that there are also Helicobacter that do not inhabit the stomach, although why some of them have gastric adapted and some not is as yet unknown [13]. 

Inhibition of the dinuclear Ni(II) enzyme urease by Bi(III) thiolates may be important for its antibacterial activity. Helicobacter pylori relies on urease for the production of ammonia which allows survival under the highly acidic conditions of the gastric lumen and mucosa. Bismuth(III) mercaptoethanol complexes are ca. 103 more active inhibitors than mercaptoethanol alone (466). The thiol can bind directly to Ni(II) in the active site and also form a disulfide with a Cys residue in the active site cavity (467). 

A conceptual model of the means whereby ammonia production from urease activated by gastric acidity may damage the mucosa. In acid, the impermeant ammonium ion is generated, but then with neutralization, the concentration of the diffusible ammonia increases. Entry of this into cells will result in alkalinization and perhaps cytokine release. 

Miederer SE, Grubel PG. Profound increase of Helicobacter pylori urease activity in gastric antral mucosa at low pH. Dig Dis Sci 1996 41 944-949. 

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