Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:6.3.4.6 (urease)
 7,490 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hyperammonemia interferes with normal brain function. The effect of ammonia on free and membrane-bound lysosomal enzymes and on mucopolysaccharide metabolism was studied in cultured rat brain cells (ROC-1, hybridoma between C6-astrocytoma and oligodendrocytes). Intralysosomal ammoniagenesis was achieved from urea by endocytosed Jackbean urease followed by incubation of the cultures with urea. The intralysosomal location of urease was evidenced by the protective effects of leupeptin and urea on the stability of intracellular urease. Ammonia formed from urea resulted in an increased secretion of lysosomal arylsulfatase-A (AS-A), but not of the membrane-bound lysosomal beta-glucosidase into the culture medium, thus intralysosomal AS-A activity decreased. Lysosomal, membrane-bound beta-glucosidase activity increased, presumably due to intralysosomal proteolytic protection following an increased lysosomal pH. Intralysosomal ammoniagenesis temporarily impaired 35SO4-glycosaminoglycan degradation of prelabeled cells. The results support the hypothesis that hyperammonemic states may interfere with lysosomal functions in vivo as well in cultured cells.
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PMID:Intralysosomal generation of ammonia from urea by endocytosed urease results in secretion of free lysosomal arylsulfatase-A and increased activity of membrane-bound beta-glucosidase in cultured brain cells. 168 84

The mechanism by which Helicobacter pylori, a noninvasive bacterium, initiates chronic antral gastritis in humans is unknown. We now show that H. pylori releases products with chemotactic activity for monocytes and neutrophils. This chemotactic activity was inhibited by antisera to either H. pylori whole bacteria or H. pylori-derived urease. Moreover, surface proteins extracted from H. pylori and purified H. pylori urease (a major component of the surface proteins) exhibited dose-dependent, antibody-inhibitable chemotactic activity. In addition, a synthetic 20-amino acid peptide from the NH2-terminal portion of the 61-kD subunit, but not the 30-kD subunit, of urease exhibited chemotactic activity for monocytes and neutrophils, localizing the chemotactic activity, at least in part, to the NH2 terminus of the 61-kD subunit of urease. The ability of leukocytes to chemotax to H. pylori surface proteins despite formyl-methionyl-leucyl-phenylalanine (FMLP) receptor saturation, selective inhibition of FMLP-mediated chemotaxis, or preincubation of the surface proteins with antiserum to FMLP indicated that the chemotaxis was not FMLP mediated. Finally, we identified H. pylori surface proteins and urease in the lamina propria of gastric antra from patients with H. pylori-associated gastritis but not from uninfected subjects. These findings suggest that H. pylori gastritis is initiated by mucosal absorption of urease, which expresses chemotactic activity for leukocytes by a mechanism not involving N-formylated oligopeptides.
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PMID:Surface proteins from Helicobacter pylori exhibit chemotactic activity for human leukocytes and are present in gastric mucosa. 173 14

Urease (urea amidohydrolase, EC 3.5.1.5) catalyzes the hydrolysis of urea to yield ammonia and carbon dioxide. Research on this enzyme has gained momentum since the discovery of Helicobacter pylori as a causative agent of human gastritis. The remarkably high urease activity of each organism has served as the basis of diagnostic tests for the presence of the organism in the urease biopsy test and urea breath test. Urease undoubtedly plays a central role in H. pylori pathogenesis. Hydrolysis of urea with generation of ammonia may enable survival of this acid-sensitive organism in the gastric mucosa. Ammonia generated by urea hydrolysis may also produce severe cytotoxic effects within gastric epithelium. The enzyme also elicits a strong immune response during acute infection, suggesting that this abundant antigen is readily available to the immune system. An increase in serum IgG titer is predictive of ongoing infection. Much progress has been made with regard to the molecular biology of urease. The high molecular weight protein (estimated by several investigators to be 300-520 kDa) has been purified, revealing two distinct subunits of 29.5 kDa and 66 kDa, a unique subunit structure as compared with other microbial ureases. However, amino acid sequences are nevertheless well conserved when compared with other bacterial ureases and that of the jack bean, Canavalia ensiformis. Furthermore, genes encoding urease of H. pylori have been cloned, sequenced, and amplified by the polymerase chain reaction.
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PMID:Helicobacter pylori urease: properties and role in pathogenesis. 177 23

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

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 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

Proteus mirabilis, a common cause of urinary tract infection, can lead to serious complications including pyelonephritis. Adherence factors, urease, and hemolysin may be virulence determinants. These factors were compared for bacteria cultured from 16 patients with acute pyelonephritis and 35 with catheter-associated bacteriuria and for 20 fecal isolates. Pyelonephritis isolates were more likely (P less than .05) to express the mannose-resistant/Proteus-like (MR/P) hemagglutinin in the absence of mannose-resistant/Klebsiella-like (MR/K) hemagglutinin than were catheter-associated or fecal isolates. Pyelonephritis isolates produced urease activity of 63 +/- 27 (mean +/- SD) mumol of NH3/min/mg of protein, not significantly different from catheter-associated or fecal isolates. Hybridization of Southern blots of P. mirabilis chromosomal DNA with two urease gene probes demonstrated that urease gene sequences were conserved in all isolates. Geometric mean of reciprocal hemolytic titers for pyelonephritis isolates was 27.9; for urinary catheter isolates, 18.0; and for fecal isolates, 55.7 (not significantly different, P greater than .1). Although in vivo expression of urease and hemolysin may not be reliable indexes of virulence, MR/P hemagglutination in the absence of MR/K hemagglutination may be necessary for development of pyelonephritis.
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PMID:Hemagglutinin, urease, and hemolysin production by Proteus mirabilis from clinical sources. 217 24

Struvite urolithiasis forms as a consequence of a urinary tract infection by urease-producing species of bacteria such as Proteus mirabilis. Ammonia, produced by the enzymatic hydrolysis of urea, elevates urine pH causing a supersaturation and precipitation of Mg++ as struvite (NH4MgPO4). Calcium often precipitates as well, forming the mineral carbonate-apatite (Ca10(PO4)6CO3). We have developed a procedure based on direct observation by light microscopy whereby struvite crystal growth can be quickly monitored in response to chemical changes in urine. As struvite crystals assume a characteristic shape or crystal habit based on their growth rate, the effect of urine chemistry and the action of various crystallization or urease inhibitors on struvite formation can be quickly shown. In addition preliminary effects of alkaline pH, or the presence of toxic compounds on bacteria can also be shown through their loss of motility.
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PMID:A simple technique for studying struvite crystal growth in vitro. 218 Jan 68

Reports indicate that L-carnitine administration before 100% lethal dose of ammonium acetate suppresses the symptoms of ammonia toxicity and prevents death in mice. However, we have been unable to confirm this observation. The cause of discrepancy between our results and the results of others was investigated with two models of hyperammonemia in mice: 1) that induced by intraperitoneal injection of urease and 2) that induced by intraperitoneal injection of ammonium acetate. L-Carnitine administration failed to protect mice against ammonia toxicity induced by intraperitoneal injection of urease. Mortality in mice treated with L-carnitine 30 min before injection of ammonium acetate was similar to that of controls pretreated with saline. Ammonia and urea levels in plasma, liver, and brain were also similar in both groups. However, the values were significantly lower than those in mice denied either pretreatment before the ammonium acetate challenge. These results indicate that pretreatment acts to reduce blood and tissue ammonia simply by diminishing the rate of absorption of the challenge, owing to the dilution of ammonium acetate upon mixing with the contents of the peritoneal cavity. Thus, any protocol that does not compare results of a putative protective agent with those obtained with an equal volume of solvents or saline runs the risk of ascribing protective property to the agent when the protection may, in fact, have been afforded by the solvent.
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PMID:Failure of L-carnitine to protect mice against hyperammonemia induced by ammonium acetate or urease injection. 223 23

The correlation between urease activity of Campylobacter pylori and atrophic gastritis was studied. On the basis of fundamental study on the optimal pH of C. pylori urease activity, urease activity of 38 biopsied specimens were measured under pH 5 condition, and compared with the positive ratio of C. pylori. In this study, sensitivity was 86.7%, and specificity was 87.0%, respectively. Mean urease activity of C. pylori positive specimens was 3.69 mIU/mg protein, and under this condition, C. pylori was likely to produce ammonia of 0.0218 mumole per minute, enough to damage the gastric mucosa. In addition, there was encountered high urease activity in the specimens which showed moderate glandular atrophy and severe mucosal inflammation. In conclusion, urea-urease-NH3 sequence is most likely to have some association with gastric glandular atrophy.
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PMID:[Correlation between Campylobacter pylori and chronic atrophic gastritis]. 225 Mar 90


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