Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0847097 (acidity)
 15,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Helicobacter pylori is a neutralophilic, gram-negative, ureolytic organism that is able to colonize the human stomach but does not survive in a defined medium with a pH <4.0 unless urea is present. In order to live in the gastric environment, it has developed a repertoire of acid resistance mechanisms that can be classified into time-independent, acute, and chronic responses. Time-independent acid resistance depends on the structure of the organism's inner and outer membrane proteins that have a high isoelectric point, thereby reducing their proton permeability. Acute acid resistance depends on the constitutive synthesis of a neutral pH optimum urease that is an oligomeric Ni(2+)-containing heterodimer of UreA and UreB subunits. Gastric juice urea is able to rapidly access intrabacterial urease when the periplasmic pH falls below approximately 6.2 owing to pH-gating of a urea channel, UreI. This results in the formation of NH3, which then neutralizes the bacterial periplasm to provide a pH of approximately 6.2 and an inner membrane potential of -101 mV, giving a proton motive force of approximately -200 mV. UreI is a six-transmembrane segment protein, with homology to the amiS genes of the amidase gene cluster and to UreI of Helicobacter hepaticus and Streptococcus salivarius. Expression of these UreI proteins in Xenopus oocytes has shown that UreI of H. pylori and H. hepaticus can transport urea only at acidic pH, whereas that of S. salivarius is open at both neutral and acidic pH. Site-directed mutagenesis and chimeric analysis have identified amino acids implicated in maintaining the closed state of the channel at neutral pH and other amino acids that play a structural role in channel function. Deletion of ureI abolishes the ability of the organism to survive in acid and also to colonize the mouse or gerbil stomach. However, if acid secretion is inhibited in gerbils, the deletion mutants do colonize but are eradicated when acid secretion is allowed to return, showing that UreI is essential for gastric survival and that the habitat of H. pylori at the gastric surface must fall to pH 3.5 or below. The chronic response is from increased Ni(2+) insertion into the apo-enzyme, which results in a threefold increase in urease, which is also dependent on expression of UreI. This allows the organism to live in either gastric fundus or gastric antrum depending on the level of acidity at the gastric surface. There are other effects of acid on transcript stability that may alter levels of protein synthesis in acid. Incubation of the organism at acidic pH also results in regulation of expression of a variety of genes, such as some outer membrane proteins, that constitutes an acid tolerance response. Understanding of these acid resistance and tolerance responses should provide novel eradication therapies for this carcinogenic gastric pathogen.
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PMID:The gastric biology of Helicobacter pylori. 1247 Nov 60

Helicobacter pylori colonizes the antral mucosa of the human stomach. There is a controversy as to whether the microorganism is exposed to acidity in its ecological niche. In vitro, the microorganism requires urease for gastric colonization and survival at pH < 4.0. UreI encodes an acid activated urea channel enabling urea access to intrabacterial urease at acidic pH. UreI is also necessary for survival at pH < 4.0. However, the role of UreI for both intragastric transit and colonization of the epithelial gastric mucosa has never been analyzed in detail. We therefore infected gerbils, whose intragastric pH and response to infection resemble those of man, with H. pylori G1.1 wild type bacteria and their corresponding isogenic ureI mutants. Inhibitors of gastric acid secretion and colonization were used for manipulation of gastric pH. Gastric colonization was determined by urease assay and PCR. Gastric pH was measured with pH electrodes. Whereas H. pylori wild type or ureI complemented ureI knockout bacteria colonized the antrum, ureI deletion mutants were unable to colonize. However, continuous inhibition of acid secretion resulted in gastric colonization by the ureI mutants, as also observed with the wild type strain. Restoration of acid secretion resulted in eradication of ureI mutants but not wild type bacteria. The data show that ureI is essential for both gastric transit after inoculation and mucosal colonization in the untreated stomach. The eradication of ureI mutants following restoration of acid secretion suggests that the organism is exposed to pH < 4.0 at the surface of the antral mucosa and that UreI provides a target for specific monotherapy of H. pylori infections.
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PMID:Expression of UreI is required for intragastric transit and colonization of gerbil gastric mucosa by Helicobacter pylori. 1255 85

The aim of this study was to investigate the dietary and physiological effects of condensed tannin ingestion on foregut fermenters, using Thallomys nigricauda, a folivorous rodent, as a model. We initially investigated the variability in physiological parameters, such as daily body mass (DMb), daily feed intake, daily fecal energy loss (FE), daily energy intake (DEI), daily urine pH, and daily urinary ammonia and urea concentrations, in response to different diets with low condensed tannin levels. This experiment was conducted to identify which physiological variables showed the least variation in the absence of tannin. In a second experiment, we investigated the response of the same dietary and physiological parameters to the effects of high dietary condensed tannin ingestion in T. nigricauda. We hypothesized that DMb, daily feed intake, FE, and DEI of T. nigricauda would be adversely affected by high dietary tannin content. We predicted that detoxification activity by T. nigricauda would increase at higher tannin levels. Ingestion of tannins affected the nutritional status of T. nigricauda, as shown by a decrease in body mass at high tannin levels. We also found that fewer ammonium ions were excreted in the urine by T. nigricauda, as would be expected if this were a means of regulating metabolic acidosis. The urine produced was more alkaline. This result indicates that T. nigricauda is not metabolizing these allelochemicals. Urea production was initially reduced, indicating conservation of bicarbonate ions that will neutralize blood acidity if there is detoxification. A diet choice experiment showed that tree rats avoid high tannin diets, even to the extent that they lose body mass on an alternative diet. This last-mentioned result is noteworthy because previous studies of the effects of tannins on herbivorous mammals have shown that there is physiological control rather than behavioral avoidance of the negative effects of tannin ingestion.
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PMID:Effects of Acacia condensed tannins on urinary parameters, body mass, and diet choice of an Acacia specialist rodent, Thallomys nigricauda. 1277 47

A new method for the determination of micro amount of gold with N1923 levextrel resin by flow injection on-line separation and flame atomic absorption spectrometry is described. Au (III) absorbed on the resin can be eluted quantitatively using sulphuric-urea solution. The absorption is carried out in 1.0 mol.L-1 HCl medium and the enhancement factor of 32 is achieved for a loading period of 90 s. The detection limit is 0.001 microgram.mL-1. The flow rate of sample injection, the time of extraction, the flow rate of enrichment, the concentration and acidity of eluting and the effect of coexistence element are studied by flame atomic absorption spectrometry. The recoveries of Au are 98.3%-101%. The developed method has been applied to the determination of trace gold in water samples with satisfactory results.
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PMID:[Determination of trace gold by on-line enrichment flow injection flame atomic absorption spectrometry with N1923 levextrel resin]. 1293 75

Metal-free tetrasulfophthalocyanine was synthesized by the reaction of triammonium salt of 4-sulfophalic acid with urea, using antimony powder as catalyst. The aggregation of this compound in aqueous and aqueous alcoholic solutions(MeOH, EtOH, ArOH) has been studied by electronic absorption spectra. The result shows that several factors such as the composition of the solvent, the acidity of solution, influence the extent of the aggregation. The dimerisation constant (Kd) of the titled compound in different solvents is reported.
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PMID:[Study on the aggregation of metal-free tetrasulfophthalocyanine in solutions]. 1294 17

Changes characteristic of an inflammatory reaction caused by the injection of an injurious agent into the peritoneal cavity were measurable by the quantity of peritoneal fluid, by the number of leucocytes that entered the cavity, and by the abundance of exuded protein. Inflammation increased in severity along with ion dissociation and increase of the valence of electrolytes. With chlorides, sulfates, and nitrates it increased in each instance with the valence of their basic ions. The reactions caused by sodium chloride, sodium sulfate, and sodium citrate increased with the valence of their acid ions. Salts of heavy metals which fix and precipitate proteins caused more active inflammation than did other electrolytes. Histamine and arginine caused active inflammatory reactions with similar characteristics. The amino compounds, urea, citrulline, and creatinine, glycine, alanine, histidine, arginine, and histamine, produced inflammatory reaction in the order of severity with which, in foregoing experiments, they had caused necrosis when injected into the dermis. The acids and alkalis that were tested caused active inflammation when their acidity approached pH 1 or their alkalinity pH 11 respectively, but with approximate neutrality the inflammatory reaction became scant. These changes were in accord with the extent of necrosis when acid or alkalis, in foregoing experiments, were injected into the dermis. When histamine or arginine combines with hydrochloric acid to form histamine dihydrochloride or arginine monohydrochloride alkalinity is lost and inflammatory reactions caused by the hydrochlorides are relatively mild. The characteristic changes which accompany histamine and arginine do not occur. The combination of histamine with phosphoric acid to form histamine acid phosphate has similar relation to histamine. Inflammatory reactions caused by monobasic, dibasic, and tribasic sodium phosphate increased in activity in accord with increasing alkalinity referable to the basic ions of these salts. The activity of inflammatory reactions has been found to vary in accord with the chemical constitution of the injurious agents that have been tested.
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PMID:On the relation of inflammation to the chemical constitution of injurious agents. On the pharmacology of inflammation. 1394 Feb 8

The influence of different denaturants on the phosphorescence spectrum and lifetime decay of Escherichia coli alkaline phosphatase (AP) was investigated. Phosphorescence intensity and lifetime of tryptophan residue (Trp-109) decrease upon addition of guanidine hydrochloride, ethylene diamine tetraacetic acid, and urea or decreasing acidity. The experiments show that AP undergoes different pathways with different denaturants and that the activation energy data, DeltaS degrees (not equal) and deltaH degrees (not equal) further confirm that there is a stable intermediate state between the folded and unfolded AP states in solution.
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PMID:Study on Escherichia coli alkaline phosphatase conformation by phosphorimetry in the presence of denaturant. 1458 94

Ureagenesis in the liver consumes up to 1,000 mmol of HCO3-/day in humans as a result of 2NH4+ + 2HCO3- --> urea + CO2 + 3H2O. Whether the liver contributes to the regulation of acid-base equilibrium by controlling the rate of ureagenesis and, therefore, HCO3- consumption in response to changes in plasma acidity has not been adequately evaluated in humans. Rates of ureagenesis were measured in eight healthy volunteers during control, chronic metabolic acidosis (induced by oral administration of CaCl2 3.2 mmol.kg body wt-1.day-1 for 11 days), and recovery as well as during bicarbonate infusion (200 mmol over 240 min; acute metabolic alkalosis). Rates of ureagenesis were correlated negatively with plasma HCO3- concentration both during adaption to metabolic acidosis and during the chronic, steady-state phase. Thus ureagenesis, an acidifying process, increased rather than decreased in metabolic acidosis. During bicarbonate infusion, rates of ureagenesis decreased significantly. Thus ureagenesis did not appear to be involved in the regulated elimination of excess HCO3-. The finding of a negative correlation between ureagenesis and plasma HCO3- concentration over a wide range of HCO3- concentrations, altered both chronically and acutely, suggests that the ureagenic process per se is maladaptive for acid-base regulation and that ureagenesis has no discernible homeostatic effect on acid-base equilibrium.
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PMID:Ureagenesis: evidence for a lack of hepatic regulation of acid-base equilibrium in humans. 1465 59

The aim of this study was to investigate the effects of the oral administration of stobadine (STB), a neuro- and cardioprotective drug with high antioxidant properties, on selective biochemical variables in pregnant and lactating mice. STB was administered orally at a dose of 50 mg/kg from day 15 of gestation to day 21 of lactation. Creatinine and urea were determined in serum, while acidity, proteins, glucose, ketones, bilirubin, urobilinogen, blood and creatinine were determined in urine from females on days 0, 15 and 18 of gestation and on days 7, 14, 21, and 28 postpartum (pp). In the biochemical variables investigated, no significant differences in STB-treated animals compared with controls were recorded on any of the days studied. Histopathological examination of kidney tissue did not reveal any adverse effect of STB administration.
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PMID:Determination of selective biochemical variables in pregnant and lactating mice after stobadine administration. 1468 99

The size and complexity of many pH-gated channels have frustrated the development of specific structural models. The small acid-activated six-membrane segment urea channel of Helicobacter hepaticus (HhUreI), homologous to the essential UreI of the gastric pathogen Helicobacter pylori, enables identification of all the periplasmic sites of proton gating by site-directed mutagenesis. Exposure to external acidity enhances [(14)C]urea uptake by Xenopus oocytes expressing HhUreI, with half-maximal activity (pH(0.5)) at pH 6.8. A downward shift of pH(0.5) in single site mutants identified four of six protonatable periplasmic residues (His-50 at the boundary of the second transmembrane segment TM2, Glu-56 in the first periplasmic loop, Asp-59 at the boundary of TM3, and His-170 at the boundary of TM6) that affect proton gating. Asp-59 was the only site at which a protonatable residue appeared to be essential for pH gating. Mutation of Glu-110 or Glu-114 in PL2 did not affect the pH(0.5) of gating. A chimera, where the entire periplasmic domain of HhUreI was fused to the membrane domain of Streptococcus salivarius UreI (SsUreI), retained the pH-independent properties of SsUreI. Hence, proton gating of HhUreI likely depends upon the formation of hydrogen bonds by periplasmic residues that in turn produce conformational changes of the transmembrane domain. Further studies on HhUreI may facilitate understanding of other physiologically important pH-responsive channels.
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PMID:Mechanism of proton gating of a urea channel. 1470 5


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