Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.5.1.5 (urease)
 7,257 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mechanism of the hypergastrinaemia associated with Helicobacter pylori infection is unknown. It may be an effect of the ammonia produced by the bacterium near the antral epithelial surface. We have examined the effect on serum gastrin of inhibiting H pylori urease activity with acetohydroxamic acid in six duodenal ulcer patients. On day 1 the fasted patients received placebo tablets at 8 am, a peptide meal at 10 am, and a 14C urea breath test at 11.30 am. The next day 750 mg acetohydroxamic acid was administered orally in place of the placebo. The median (range) 30 minute breath test value (dose/mmol CO2 X kg body wt X 100) was 152 (111-335) on day 1, but only 22 (14-95) the next day (p less than 0.03). Further studies performed in one subject confirmed that acetohydroxamic acid lowered the ammonium concentration and raised the urea concentration in gastric juice. The inhibition of urease activity and ammonia production did not result in a fall in the basal gastrin concentration or in the median integrated gastrin response to the peptide meal, which was 78 ng/1.h (range 21-222) on day 1 and 79 ng/1.h (33-207) the next day. Ten days after acetohydroxamic acid, the urea breath test values were similar to those before treatment. This study shows that the raised gastrin concentration in patients with H pylori infection is not directly related to the organism's urease activity. It also shows that temporary suppression of H pylori urease activity does not clear the infection.
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PMID:Effect of inhibition of Helicobacter pylori urease activity by acetohydroxamic acid on serum gastrin in duodenal ulcer subjects. 188 67

By using our new infection stone model of a rat, we evaluated the effect of a novel urease inhibitor, N-(pivaloyl)glycinohydroxamic acid (P-GHA), on the formation of an infection bladder stone. The oral dosing of P-GHA significantly inhibited the elevation of the urinary ammonia level of rats having the urinary tract infection with Proteus mirabilis. A short term regimen (7 d, 730 +/- 38 mg/kg) with P-GHA significantly inhibited the development of the infection bladder stone. Furthermore, a long term combination regimen (11 d) of P-GHA and aminobenzylpenicillin markedly inhibited the development of the infection bladder stone, and also caused a very slight renal impairment to the rats tested in contrast with the method of Vermeulen et al. Our infection stone model in rats, therefore, seems to be useful for the evaluation of therapeutic agents in long term examinations.
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PMID:Evaluation of effects of novel urease inhibitor, N-(pivaloyl)glycinohydroxamic acid on the formation of an infection bladder stone using a newly designed urolithiasis model in rats. 189 94

Ureidoglycolate is an intermediate of allantoin catabolism in ureide-transporting legumes. This report describes the first purification of ureidoglycolate degrading activity (UGDA) from plant tissue in which the enzyme has been separated from urease. The enzyme from developing fruits of Phaseolus vulgaris has been purified 48-fold to give a preparation free of allantoinase and urease activity. UGDA was inhibited by EDTA while the Vmax was increased in the presence of Mn2+. The Km values for ureidoglycolate in the presence and the absence of Mn2+ were 2.0 and 5.4 mM, respectively. In the absence of Mn2+ UGDA was heat labile at 40 degrees C, but in the presence of Mn2+ the activity was stable up to temperatures of 60 degrees C. The Mr of UGDA was determined to be 300,000 by gel filtration chromatography and the pH optimum ranged from pH 7.0 to 8.5. Ammonia was determined to be the nitrogen-containing product of UGDA by a microdiffusion assay. This enzyme should therefore be described as ureidoglycolate amidohydrolase. The activity was shown to be associated with peroxisomes by fractionation of a crude extract on a sucrose density gradient. The products of ureidoglycolate degradation are glyoxylate, ammonia, and presumably carbon dioxide, which can be readily utilized by pathways of metabolism that are known to be present in this organelle.
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PMID:Ureidoglycolate amidohydrolase from developing French bean fruits (Phaseolus vulgaris [L.].). 191 Feb 98

H. pylori is a highly virulent organism as evidenced by its low infective dose and widespread high prevalence in human populations. Its virulence is achieved through its ability to survive in a moist environment and its massive urease production which allows it to survive in the acidic gastric juice long enough to colonize the gastric mucus. Gastric colonization is facilitated by cell wall associated lectins which permit the bacterium to bind to gastric mucus and the gastric epithelial cell. Once in this location, H. pylori produces several enzymes which may harm the gastric epithelium, particularly urease (through ammonia generation) and phospholipases A and C. H. pylori also weakens the gastric mucous layer by digesting its glycoproteins and lipids, making the mucus less hydrophobic and more water soluble. Helicobacter pylori attracts phagocytic cells, inducing both acute and chronic inflammation as well as an antibody response. Persistence of H. pylori in the mucosa may be enhanced by its cytotoxin and catalase production, by which it survives after phagocytosis by neutrophils.
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PMID:Virulence and pathogenicity of Helicobacter pylori. 191 16

Ammonia, released in the gastric mucosa by the action of Helicobacter pylori urease on transuded plasma urea, curtails the biosynthesis of mucus and/or causes the mucus to be disassembled at the mucosal surface. These changes facilitate colonisation by H pylori and may promote gastric ulcer formation.
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PMID:Hypothesis: Helicobacter pylori, urease, mucus, and gastric ulcer. 196 87

The effects of hyperammonemia on brain function have been studied in three different experimental models in the rat: acute liver ischemia, urease-treated animals and methionine sulfoximine-treated animals. To quantify the development of encephalopathy, clinical grading and electroencephalographic spectral analysis were used as indicators. In all three experimental models brain ammonia concentrations increased remarkably associated with comparable increases in severity of encephalopathy. Furthermore, in vivo 1H-nuclear magnetic resonance spectroscopy of a localized cerebral cortex region showed a decrease in glutamate concentration in each of the aforementioned experimental models. This decreased cerebral cortex glutamate concentration was confirmed by biochemical analysis of cerebral cortex tissue post mortem. Furthermore, an increase in cerebral cortex glutamine and lactate concentration was observed in urease-treated rats and acute liver ischemia rats. As expected, no increase in cerebral cortex glutamine was observed in methionine sulfoximine-treated rats. These data support the hypothesis that ammonia is of key importance in the pathogenesis of acute hepatic encephalopathy. Decreased availability of cerebral cortex glutamate for neurotransmission might be a contributing factor to the pathogenesis of hyperammonemic encephalopathy. A surprising new finding revealed by 1H-nuclear magnetic resonance spectroscopy was a decrease of cerebral cortex phosphocholine compounds in all three experimental models. The significance of this finding, however, remains speculative.
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PMID:Changes in brain metabolism during hyperammonemia and acute liver failure: results of a comparative 1H-NMR spectroscopy and biochemical investigation. 197 48

The prevalence of Helicobacter pylori (HP) in the gastric mucosa of patients with chronic atrophic gastritis has been reported to be significantly higher than in normal mucosa. To clarify the role of HP in the etiology of chronic atrophic gastritis, we assessed the effect of ammonia on the gastric mucosal structure in rats, since HP has a strong urease activity and produces abundant amounts of ammonia. Ammonia administered orally at 0.01% and 0.1% as drinking water for two to four weeks decreased the mucosal thickness and the parietal cell number and oxyntic gland number in a dose- and time-dependent manner. The decrease of mucosal thickness was significantly greater in the antral mucosa than in the body mucosa. The border between the antral and body mucosa shifted toward the cardia, reflecting the decrease in oxyntic gland numbers. Furthermore, intracellular mucin was also decreased in a dose- and time-dependent manner, especially in the antral mucosa. Thus, ammonia chronically administered orally in rats led to changes in gastric mucosal structures and functions. The results suggest that the ammonia produced by HP partly plays an etiologic role in chronic atrophic gastritis.
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PMID:Chronic effect of intragastric ammonia on gastric mucosal structures in rats. 198 2

It has been proposed that the hypergastrinaemia in subjects with Helicobacter pylori infection is caused by the action of the ammonia produced by the organism's urease activity on the antral G cells. To investigate this hypothesis we examined the effect on plasma gastrin of increasing the bacterium's ammonia production by infusing urea intragastrically to eight H pylori positive duodenal ulcer patients. After a 60 minute control intragastric infusion of dextrose solution at 2 ml/minute, a similar infusion containing urea (50 mmol/l) was continued for four hours. During the urea infusion, the median gastric juice urea concentration rose from 1.1 mmol/l (range 0.3-1.6) to 15.5 mmol/l (range 7.9-21.3) and this resulted in an increase in the ammonium concentration from 2.3 mmol/l (range 1.3-5.9) to 6.1 mmol/l (range 4.2-11.9) (p less than 0.01). This appreciable rise in ammonia production did not result in any change in the plasma gastrin concentration. The experiment was repeated one month after eradication of H pylori, at which time the median basal gastrin was 20 ng/l (range 15-25), significantly less than the value before eradication (30 ng/l range 15-60) (p less than 0.05). On this occasion, the gastric juice ammonium concentration was considerably reduced at 0.4 mmol/l (range 0.1-0.9) and the urea infusion did not raise the ammonium concentration or change the plasma gastrin concentration. In conclusion, augmenting H pylori ammonia production does not cause any early change in plasma gastrin.
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PMID:Effect of increasing Helicobacter pylori ammonia production by urea infusion on plasma gastrin concentrations. 199 33

Ureaplasmas killed mice within 5 min after intravenous injection. The 50% lethal dose of whole ureaplasmal organisms was 32 micrograms per mouse, a value also found for crystalline jackbean urease. The reaction was specific to urease, since protection was afforded by intraperitoneal injection of 200 micrograms of flurofamide, a potent urease inhibitor. The finding that a similar lethal effect was produced by injection of 200 mumol of NH4+ indicates that the toxicity of urease is mediated by ammonium ions or free ammonia.
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PMID:Virulence of ureaplasmal urease for mice. 199 18

Concentrated broth culture supernatants from 50 to 60% of Helicobacter pylori strains induce eukaryotic cell vacuolation in vitro. A quantitative assay for cell vacuolation was developed on the basis of the rapid uptake of visibly vacuolated HeLa cells was significantly greater than that of nonvacuolated cells. By using the rapid NRU assay, we sought to determine the roles of H. pylori cytotoxin, urease, and ammonia in the vacuolation of HeLa cells. The NRU of HeLa cells incubated in medium containing ammonium chloride or ammonium sulfate was significantly greater than that of cells incubated in medium alone. In addition, ammonium salts augmented the NRU induced by H. pylori supernatants. The NRU induced by jack bean urease was augmented by the addition of urea to cell culture medium; this suggests that urease-mediated NRU occurs via the generation of ammonia. Acetohydroxamic acid blocked the NRU induced by jack bean urease and urea but failed to block the uptake induced by H. pylori supernatants. Supernatant from a non-urease-producing H. pylori mutant strain induced NRU identical to that of the urease-positive parental strain. These observations indicate that the vacuolating activity in H. pylori supernatants is not mediated solely by urease activity but that it may be potentiated by urease-mediated ammonia production.
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PMID:Effect of urease on HeLa cell vacuolation induced by Helicobacter pylori cytotoxin. 200 8


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