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)

Urease (urea amidohydrolase; EC 3.5.1.5) catalyzes the hydrolysis of urea to yield ammonia and carbamate. The latter compound spontaneously decomposes to yield another molecule of ammonia and carbonic acid. The urease phenotype is widely distributed across the bacterial kingdom, and the gene clusters encoding this enzyme have been cloned from numerous bacterial species. The complete nucleotide sequence, ranging from 5.15 to 6.45 kb, has been determined for five species including Bacillus sp. strain TB-90, Klebsiella aerogenes, Proteus mirabilis, Helicobacter pylori, and Yersinia enterocolitica. Sequences for selected genes have been determined for at least 10 other bacterial species and the jack bean enzyme. Urease synthesis can be nitrogen regulated, urea inducible, or constitutive. The crystal structure of the K. aerogenes enzyme has been determined. When combined with chemical modification studies, biophysical and spectroscopic analyses, site-directed mutagenesis results, and kinetic inhibition experiments, the structure provides important insight into the mechanism of catalysis. Synthesis of active enzyme requires incorporation of both carbon dioxide and nickel ions into the protein. Accessory genes have been shown to be required for activation of urease apoprotein, and roles for the accessory proteins in metallocenter assembly have been proposed. Urease is central to the virulence of P. mirabilis and H. pylori. Urea hydrolysis by P. mirabilis in the urinary tract leads directly to urolithiasis (stone formation) and contributes to the development of acute pyelonephritis. The urease of H. pylori is necessary for colonization of the gastric mucosa in experimental animal models of gastritis and serves as the major antigen and diagnostic marker for gastritis and peptic ulcer disease in humans. In addition, the urease of Y. enterocolitica has been implicated as an arthritogenic factor in the development of infection-induced reactive arthritis. The significant progress in our understanding of the molecular biology of microbial ureases is reviewed.
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PMID:Molecular biology of microbial ureases. 756 14

The urea breath test exploits the urease enzyme of Helicobacter pylori. The hydrolysis of labelled urea releases labelled carbon dioxide that is excreted in the breath. Distribution of urea throughout the stomach prevents sampling errors and allows for semiquantitative assessment of the extent of Helicobacter pylori infection. The urea breath test is very specific and sensitive and can be proposed as the method of choice for detecting Helicobacter pylori infection in ulcer patients before and after eradicating treatment as well as in epidemiological studies.
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PMID:The urea breath test: a non-invasive clinical tool for detecting Helicobacter pylori infection. 757 92

Noninvasive detection of Helicobacter pylori (HP) requires serum or salivary antibody testing or the CO2 breath test. Since gastric HP produces a potent urease, a meal rich in 13C-labeled urea should lead to a measurable quantity of isotopic CO2 in the serum. This study investigates the feasibility, sensitivity, specificity, and potential of the measurement of serum 13C-bicarbonate (13CHCO3) in determining the presence of gastric HP. Nineteen patients with upper gastrointestinal symptoms assessed by intensity-duration questionnaire underwent endoscopy and biopsies for histology, Giemsa stain, and urease activity testing by CLOtest. Patients also consumed a 13C-urea-rich meal (5 mg/kg body weight, 99% 13C, MSD Isotopes, Montreal Canada). Serum was collected every 30 min for 3 h for quantitative determination of 13C by mass spectrometry. Fractional elevation of 13C after the enriched meal was then correlated with endoscopy, histology, and CLOtest. Fourteen of the 19 patients studied had histologic evidence of gastritis; 11 of 19 had positive CLOtest and had HP by histology and Giemsa stain. All HP-positive patients had significant elevation of 13CHCO3, compared with HP-negative patients. The mean maximum absolute change from baseline was 15.3 delta 13CHCO3 (range, 6.7-29.9) and occurred from 15 to 90 min; 13CHCO3 in HP-negative patients was significantly less (p < 0.05) than HP-positive patients with a mean value of 2.3 delta 13CHCO3 (range, 0-5.3). We conclude that serum 13CHCO3 analysis accurately reflects HP gastritis. This novel method is noninvasive, less labor intensive, less time consuming, and may have a value as a diagnostic screening tool for humans or in the assessment of the results of therapy in patients with HP infection.
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PMID:Serum 13C-bicarbonate in the assessment of gastric Helicobacter pylori urease activity. 767 76

The crystal structure of urease from Klebsiella aerogenes has been determined at 2.2 A resolution and refined to an R factor of 18.2 percent. The enzyme contains four structural domains: three with novel folds playing structural roles, and an (alpha beta)8 barrel domain, which contains the bi-nickel center. The two active site nickels are 3.5 A apart. One nickel ion is coordinated by three ligands (with low occupancy of a fourth ligand) and the second is coordinated by five ligands. A carbamylated lysine provides an oxygen ligand to each nickel, explaining why carbon dioxide is required for the activation of urease apoenzyme. The structure is compatible with a catalytic mechanism whereby urea ligates Ni-1 to complete its tetrahedral coordination and a hydroxide ligand of Ni-2 attacks the carbonyl carbon. A surprisingly high structural similarity between the urease catalytic domain and that of the zinc-dependent adenosine deaminase reveals a remarkable example of active site divergence.
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PMID:The crystal structure of urease from Klebsiella aerogenes. 775 94

Assembly of protein metallocenters is not well understood. Urease offers a tractable system for examination of this process. Formation of the urease metallocenter in vivo is known to require four accessory proteins: UreD, postulated to be a urease-specific molecular chaperone; UreE, a nickel(II)-binding protein; and UreF and UreG, of unknown function. Activation of purified Klebsiella aerogenes urease apoprotein was accomplished in vitro by providing carbon dioxide (half-maximal activation at approximately 0.2 percent carbon dioxide) in addition to nickel ion. Activation coincided with carbon dioxide incorporation into urease in a pH-dependent reaction (pKa > or = 9, where Ka is the acid constant). The concentration of carbon dioxide also affected the amount of activation of UreD-urease apoprotein complexes. These results suggest that carbon dioxide binding to urease apoprotein generates a ligand that facilitates productive nickel binding.
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PMID:Requirement of carbon dioxide for in vitro assembly of the urease nickel metallocenter. 785 93

Recently many reports have shown a strong association between Helicobacter pylori infection in the stomach and recurrent peptic ulcer. Moreover, prospective cohort serological studies showed that H. pylori infected individuals have significantly increased rate of gastric cancer in the USA. H. pylori is a gram-negative spiral organism which has urease activity and produces ammonia and CO2 from urea, and nestles in the gastric pits and overlaying mucus gel layer. Many diagnostic methods of H. pylori infection are available; ie bacterial culture, 13C-urea breath test, histology, serum IgG antibody against H. pylori. We developed a new method, ie tissue IgA antibody against H. pylori and detection of H. pylori DNA in the gastric juice by PCR method. Triple therapies with metronidazole, bismuth compounds, and amoxicillin or tetracyclin are difficult to use in Japan because of their sever side effects. Thus, new methods with proton pump inhibitor (PPI) and amoxicillin have been introduced. We treated 14 patients of whom were H. pylori positive-active peptic ulcer with 30 mg/day of lansoprazole, a new PPI, plus 1,500 mg/day of amoxicillin for 2 weeks and 8 (57%) patients were eradicated. Gastric carcinogenesis are multi-steps and multifactorials process. Hypothetical sequence of intestinal type of gastric cancer is that superficial gastritis-->atrophic gastritis-->intestinal metaplasia-->dysplasia-->gastric cancer and H. pylori infection may play a role in the early stage of the sequence. We examined mucosal IgA antibody against H. pylori in chronic gastritis and intestinal metaplasia detected by the Tes-Tape method in 25 resected specimens after gastrectomy for gastric cancer. Positivity rates of tissue H. pylori IgA antibody were lower in the mucosa of intestinal metaplasia than in non-metaplastic gastric mucosa and were negative in carcinoma. Causal relationship between H. pylori infection and gastric cancer is not proven and factors other than H. pylori infection are also important in the gastric carcinogenesis. Finally we introduce 2 reports: (1) NIH Consensus Conference: Helicobacter pylori in peptic ulcer disease (JAMA. 1994; 272: 65-69). The consensus panel concluded that 1. ulcer patients with H. pylori infection require treatment with antimicrobial agents in addition to antisecretory drugs whether on first presentation with the illness or on recurrence; 2. the value of treating nonulcerative dyspepsia patients with H. pylori infection remains to be determined; and 3. the interesting relationship between H. pylori infection and gastric cancer requires further exploration. (2) World Health Organization: Working Group Meeting (Reported in World Congress of Gastroenterology, Los Angeles, 1994). H. pylori plays a causal role in the chain of events leading to cancer of the stomach. Group I: definite carcinogen.
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PMID:[Helicobacter pylori in peptic ulcer and gastric cancer]. 785 88

Tests were conducted to determine the effects of Profenfos [(0-(4-bromo-2-chlorophenyl) 0-ethyl S-n-propyl-phosphorothioat] on fungal populations and some activities in soil. Profenfos (at 5.4 micrograms active ingredient/g dry soil), has a significant adverse effect on the count of total fungi after 2, 4 and 6 weeks after treatment. This effect was completely alleviated after longer incubation. Incorporation of this insecticide into the agar medium inhibited the total count of soil fungi at 6.4 and 38.4 micrograms ml-1. Initial activation followed by a decrease in CO2 output occurred in soil treated with 5.4 micrograms a.i./g. The two doses of Profenfos accelerated urease activity for 6 weeks after soil treatment, but inhibited the enzyme activity after longer periods. An inhibitory effect on nitrate reductase activity was observed with some insecticide treatments in the early stages of incubation followed by an activation in certain cases.
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PMID:Effect of soil treatment with the organophosphorus insecticide Profenfos on the fungal flora and some microbial activities. 792 96

Urease is an enzyme found in plants and bacteria, but not mammals. It catalyzes the conversion of urea to carbon dioxide and ammonia. Ammonia shortens the life span of cells; and higher concentrations cause tissue necrosis and cytolysis. Twenty percent of total body urea is converted to ammonia by bacterial urease in the colon. Small injections of urease immunize animals by producing antiurease, a gamma globulin, which inactivates urease. Immunization eliminates the colonic conversion of urea to ammonia. Injection of urease produces ammonia intoxication making immunization hazardous. Although previously impossible, a non enzymatic urease antigen was synthesized by covalently bonding jack bean urease with glutaraldehyde. This antigen stimulated the production of antiurease that inactivates native urease. Helicobacter pylori, a potent urease producer, has been implicated in peptic ulcer, gastritis and other inflammatory bowel lesions. The pathogenicity of H pylori is dependent on its urease production. Immunization to urease can render H pylori non pathogenic. Cirrhotics develop encephalopathy and hyperammonemia because their livers fail to convert all the ammonia in portal venous blood to urea and collaterals develop by passing the liver. Colonic ammonia increases the turnover rate of colonic mucosa. Ammonia absorbed into the portal venous system is transported to the liver where it is reconverted to urea. Absorbed ammonia adversely influences liver function. Infections with urease producing organisms destroy the renal parenchyma and produce struvite stones. Urease immunization aids colonic healing and prevents uremic colitis. Absorbed ammonia is a noxious influence on the liver. Animals immunized to urease regenerate the liver faster and are less susceptible to hepatotoxins. Immunization to urease ameliorates cirrhosis. Proteus and other urease producers become non toxic and do not damage the renal parenchyma. Urease is responsible for the pathogenicity of infections with urease producing organisms. Immunization to urease renders urease producing organisms non pathogenic.
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PMID:Awakenings to the pathogenicity of urease and the requirement for continuous long term therapy. 799 80

Four microbial enzymes are known to require nickel: hydrogenase, methyl coenzyme M reductase, carbon monoxide dehydrogenase, and urease. Recent biochemical and molecular biological experiments have provided clear evidence for the existence of multiple auxiliary genes that facilitate nickel incorporation into urease and hydrogenase. Similarly, accessory factors are also likely to be required for the other two enzymes. One of the urease-related genes (ureE) encodes a cytoplasmic protein that has been purified and shown to bind nickel reversibly. We propose that the UreE protein serves as a nickel donor to urease apoprotein. A second urease-related auxiliary gene (ureG) possesses a sequence motif that is found in ATP- and GTP-binding proteins. We have shown that nickel incorporation into urease requires energy and speculate that the UreG protein may serve as an energy transducer, coupling the energy of NTP hydrolysis to metallocenter incorporation. The UreG protein is related in sequence to HypB, a protein that has been proposed to function in nickel processing in hydrogenases. Hence, the mechanisms for metallocenter biosynthesis in these two dissimilar enzymes may have evolved from a common nickel incorporation system.
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PMID:Nickel enzymes in microbes. 802 91

Two of 23 strains of Helicobacter pylori adapted from microaerobic to aerobic growth on blood agar plates incubated in humidified air. The air-adapted strains remained urease and phenylalanine deaminase positive and did not require the buffering effect of an enriched CO2 atmosphere for growth. The significance of this phenomenon remains to be determined as the two strains capable of aerobic metabolism were laboratory-adapted.
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PMID:Adaptation of Helicobacter pylori to aerobic growth. 807 Apr 55


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