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Urolithiasis pp 209-214 | Cite as

Urease Inhibitors in the Treatment of Infection Induced Stones: Some Chemical, Pharmacologic and Clinical Considerations

  • William N. Fishbein

Abstract

Urease, the most potent of all amidases, is widely distributed in bacteria, plants, and invertebrates, although absent from the tissues of vertebrates1. It is at present the only example known of a nickel metalloenzyme2,3, and its activity persists over a wide range of H+, urea, ammonia, and bicarbonate concentrations. When present in bacteria invading the urinary tract, it faces an environment peculiarly suited to elicit damage to the host. The potential amounts of ammonia and bicarbonate in urinary urea are, respectively, about 25x and 180x their usual levels in urine, and the hydrolysis constant of ammonium carbonate is about pH 9. Significant ureolysis will therefore result in (1) marked increase in urinary ammonia, (2) dramatic increase in urinary bicarbonate, (3) increase in urine pH leading to the appearance of carbonate and some ammonia vapor. These three factors comprise a vicious circle abetting cell damage and stone formation. They can be aborted, indirectly by bacteriostasis, and/or directly, by inhibiting urease.

Keywords

Chronic Toxicity Hydroxamic Acid Hepatic Coma Ammonium Carbonate Hydrolysis Constant 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 1981

Authors and Affiliations

  • William N. Fishbein
    • 1
  1. 1.Biochemistry DivisionArmed Forces Institute of PathologyUSA

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