Nitrogen Metabolism

Excerpt

Ammonia is the major source of nitrogen in H. pylori, and the metabolism of this bacterium seems to be adapted to an environment in which this compound is rarely limiting. As described in this chapter, ammonia is produced in various ways in H. pylori, and urease is one of the principal enzymes involved in this process. The networks regulating nitrogen assimilation commonly found in other bacteria seem to be absent in this organism. However, the low level of serine dehydratase activity in arginase-deficient strains (17) and the relationship between urease, arginase, and amidase activities (27) suggest the existence of a global nitrogen- or ammonia-dependent regulation of H. pylori metabolism.

An exceptional characteristic of H. pylori nitrogen metabolism is the close connection between ammonia production and the resistance of this organism to acidic conditions. Urease is central in this response, and the availability of urea is critical. H. pylori has redundant mechanisms for supplying intracellular urea: probably UreI, but also a high-affinity urea transport system, and an arginase, which may be important when the extracellular urea concentration decreases to very low levels. The contribution of the other ammonia-producing enzymes to the survival of H. pylori in acidic environments is unclear. Arginase is important for in vitro resistance to acidity but is apparently not essential in vivo, whereas the hydrolysis of acetamide by the AmiE amidase does not enable H. pylori to survive to acidity in vitro (Bury and De Reuse, unpublished results). Preliminary results from McGee et al. (17) suggest that the amino acid deaminases do not play an important role in protecting H. pylori against acidity.

Finally, the large amounts of ammonia generated by H. pylori are probably involved in pathogenesis. The ammonia produced by urease has been shown to be toxic for various gastric cell lines (22, 30). It has been suggested that urease activity damages the gastric epithelium by interacting with the immune system and stimulating an oxidative burst in human neutrophils (33). The hypochlorous acid generated during this stage then probably reacts with ammonia to yield the highly toxic monochloramine (3, 12).