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)

Photodissociation of fully reduced, carbonmonoxy cytochrome bo3 causes ultrafast transfer of carbon monoxide (C triple bond O) from heme iron to CuB in the binuclear site. At low temperatures, the C triple bond O remains bound to CuB for extended times. Here, we show that the binding of C triple bond O to CuB perturbs the IR stretch of an un-ionized carboxylic acid residue, which is identified as Glu286 by mutation to Asp or to Cys. Before photodissociation, the carbonyl (C=O)-stretching frequency of this carboxylic acid residue is 1726 cm-1 for Glu286 and 1759 cm-1 for Glu286Asp. These frequencies are definitive evidence for un-ionized R-COOH and suggest that the carboxylic acids are hydrogen-bonded, though more extensively in Glu286. In Glu286Cys, this IR feature is lost altogether. We ascribe the frequency shifts in the C=O IR absorptions to the effects of binding photodissociated C triple bond O to CuB, which are relay ed to the 286 locus. Conversely, the 2065 cm-1 C triple bond O stretch of CuB-CO is markedly affected by both mutations. These effects are ascribed to changes in the Lewis acidity of CuB, or to displacement of a CuB histidine ligand by C triple bond O. C triple bond O binding to CuB also induces a downshift of an IR band which can be attributed to an aromatic C-H stretch, possibly of histidine imidazole, at about 3140 cm-1. The results suggest an easily polarizable, through-bond connectivity between one of the histidine CuB ligands and the carboxylic group of Glu286. A chain of bound water molecules may provide such a connection, which is of interest in the context of the proton pump mechanism of the heme-copper oxidases.
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PMID:Fourier transform infrared evidence for connectivity between CuB and glutamic acid 286 in cytochrome bo3 from Escherichia coli. 934 Dec 7

Symptomatic gastro-oesophageal reflux disease is a common disorder characterized by pathological exposure of the distal oesophagus to acid. The management requires the control of symptoms, prevention of relapse and complications. Proton pump inhibitors are without doubt the most effective agents in the management of gastro-oesophageal reflux disease. In Helicobacter pylori-negative individuals the efficacy of ranitidine, but more pronounced of omeprazole, on the nocturnal intragastric acidity, is less than in Helicobacter pylori-positive patients. Curing the Helicobacter pylori infection in gastro-oesophageal reflux disease patients might, therefore, have the disadvantage of losing efficacy of antisecretory therapy. Conversely, several studies have shown that long-term use of proton pump inhibitors is associated with progression and worsening of body gastritis exclusively in Helicobacter pylori-positives. This observation makes Helicobacter pylori eradication indicated before starting long-term treatment with proton pump inhibitors for gastro-oesophageal reflux disease and other acid-related diseases. The data reported, so far, however, are not conclusive. The Federal Drugs Administration Advisory Committee concluded on available data, that there is no evidence that longterm proton pump inhibitors treatment leads to gastric atrophy, intestinal metaplasia or gastric cancer. Eradication of Helicobacter pylori infection might lead to reduction in the efficacy of antisecretory agents, but might prevent worsening of the gastric corpus gastritis. More data are needed to really answer these clinically relevant questions.
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PMID:Should Helicobacter pylori be eradicated before starting long-term proton pump inhibitors? 951 35

ATP-driven acidification of internal compartments of Trypanosoma cruzi epimastigotes was assayed spectrophotometrically with Acridine Orange and cells permeabilized with filipin. H+-ATPase activity was not inhibited fully by either 500 nM concanamycin A or 500 microM orthovanadate, but a combination of 5 nM concanamycin A and 25 microM vanadate completely inhibited activity, suggesting the operation of separate V-type (concanamycin-sensitive) and P-type (vanadate-sensitive) H+-ATPase activities in the permeabilized cells. This was supported by different kinetics of Acridine Orange uptake seen in the presence of the different inhibitors, and by different optimal protein (cell) concentrations for the two apparent activities. The use of different buffers further distinguished the ATPases. The V-H+-ATPase activity was stimulated by K+ and inhibited by a lack of anions or the replacement of Cl- with gluconate. The P-type H+-ATPase activity was not affected by a lack of Cl- or K+ but was substantially inhibited in a largely anion-free buffer. This inhibition could be annulled by the addition of the K+ ionophore valinomycin, which probably acted via the establishment of a countercurrent efflux of K+ from the compartment containing the P-type H+-ATPase and the relief of the potential difference generated by the electrogenic proton pump. Valinomycin showed some stimulation of P-type activity in all buffers tested, but its effects on V-H+-ATPase activity were at best transient except in a K+-free buffer, which suggested that the V-H+-ATPase was located in an organelle with relatively low [K+] that was different from that which accommodated the P-type activity. On the basis of acidity and K+ content, these organelles might correspond, in part at least, to the acidocalcisomes (V-H+-ATPase activity) and the reservosomes (P-type activity) previously identified in these cells. Both activities could also be found in the human-infective forms of the parasite, amastigotes and trypomastigotes, but the P-type activity was relatively weak in these cells types, which is correlated with a lack of reservosomes in these forms.
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PMID:Two types of H+-ATPase are involved in the acidification of internal compartments in Trypanosoma cruzi. 953 1

We have examined the coupling between somatostatin, gastrin, and gastric acidity, using sheep chronically immunized against somatostatin. All immunized sheep had high-titer (3.2 x 10(5) +/- 1.1 x 10(4) M), high-affinity (1.5 x 10(11) +/- 1.2 x 10(10) l/mol) antibodies. However, basal gastrin and gastric acidity were similar to those in control animals, indicating that an inhibitory somatostatin tone was not required for the maintenance of normal basal gastrin and gastric acidity. Omeprazole (a proton pump inhibitor) increased gastric pH to a similar extent in both the control and immunized groups but resulted in a smaller increase in plasma gastrin in the immunized sheep, thus calling into question the assumption that hypergastrinemia associated with hypochlorhydria is the result of somatostatin withdrawal. Pentagastrin- or histamine-stimulated somatostatin secretion reversed or attenuated the omeprazole-induced hypergastrinemia in control but not immunized sheep, demonstrating a functional role for somatostatin and the biological efficacy of the somatostatin immunization. In a separate series of omeprazole-treated sheep, restoration of an acidic gastric pH with intragastric HCl reversed the hypergastrinemia in both control and immunized animals. We conclude that somatostatin is not essential for the acid-mediated regulation of gastrin. The use of a chronically immunized model as opposed to the acute administration of somatostatin antibodies has important advantages in determining the steady-state regulatory role of somatostatin.
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PMID:Active immunization against somatostatin alters regulation of gastrin in response to gastric acid secretagogues. 957 58

The reverse transcription polymerase chain reaction (RT-PCR) was performed to detect genes of RNA viruses in the freshly biopsied gastric mucosa of seven patients with low gastric acidity. Although nucleoprotein genes of Sendai virus and hemmaglutinin genes of influenza virus A were not detected, nucleoprotein genes of influenza virus B were detected in samples from three of the seven patients. The first patient had had antrectomy and vagotomy for gastric ulcer, the second patient was receiving a histamine type 2 receptor blocker for gastritis, and the third patient was receiving a proton pump inhibitor for gastric ulcer. Virus isolation from gastric mucosa and from gargles was negative for all seven patients. These findings suggest that genes of influenza viruses may exist in the gastric mucosa of patients with low gastric acidity.
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PMID:Detection of genes of RNA viruses from freshly biopsied gastric mucosa by reverse transcription polymerase chain reaction. 960 41

Eukaryotic cells have developed an array of endomembrane systems that have differentiated to carry out various functions. They are involved in the pathways of endocytosis and exocytosis, and have an acidic lumenal pH ranging from 4.5 to 6.5. This review describes recent studies on the animal cell organelles and how they relate to the well studied systems of yeast. We focus mainly on (i) the primary proton pump (vacuolar type H+-ATPase) and other factors that establish acidic pH, and (ii) functions of the organelles as related to lumenal acidity.
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PMID:Diverse roles of single membrane organelles: factors establishing the acid lumenal pH. 968 12

The ability of Helicobacter pylori to survive in the varying acidity of the stomach is considered to be linked to its ability to maintain a tolerable pH in its periplasmic space by acid dependent activation of internal urease activity. Whereas survival of H pylori can occur between a periplasmic pH of 4.0 to 8.0, growth can only occur between a periplasmic pH of 6.0 to 8.0. When urease activity is only able to elevate periplasmic pH to between 4.0 and 6.0, the organisms will survive but not divide. In the absence of division, antibiotics such as clarithromycin and amoxycillin are ineffective. Proton pump inhibitors, by elevating gastric pH, would increase the population of dividing organisms and hence synergise with these antibiotics.
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PMID:The life and death of Helicobacter pylori. 976 42

In this study, we examined the effect of rabeprazole (E3810), a novel proton pump inhibitor, on gastric acidity under physiological conditions in healthy volunteers using 24-hour intragastric pH monitoring. Twenty-four-hour intragastric pH monitoring was performed three times to seven subjects randomly assigned in a cross over fashion to one of the following groups; without drug administration (basal), and with 10 mg or 20 mg of rabeprazole for four days. The median pH for 24 hours was 2.15 in the basal study, while the corresponding median pH were 5.05 and 5.90 after treatment with 10 mg and 20 mg of rabeprazole, respectively. Significant differences in the median pH were observed between the basal study and that after administration of the 10 mg and 20 mg doses of rabeprazole. The cumulative percentage of pH readings above the threshold pH 4 value, was 34.1% in the basal study, and 72.6% and 78.3% after treatment with 10 mg and 20 mg doses of rabeprazole, respectively. This result indicates that the efficacy of rabeprazole allows for substantial control of gastric acidity with once-daily dosing, and that both the 10 mg and 20 mg doses result in potent inhibition of gastric acid secretion.
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PMID:Effect of rabeprazole (E3810), a novel proton pump inhibitor, on intragastric pH in healthy volunteers. 991 6

Archaea are the most extremophilic of the acidophilic microbes, combining, in many cases, acidophilicity with hyperthermophilicity. They form one of the three branches of the phylogenetic tree, and they are specifically found within the so-called crenarchaeota, typical members of which thrive at pH 1-3 and at temperatures of 75 degrees C to nearly 100 degrees C. Despite this, these cells can maintain a near neutral cytosol, and they use H+ for chemiosmotic coupling of ADP phosphorylation. These phenomena require efficient exclusion and disposal of protons. This is achieved by multiple synergistic mechanisms that act in parallel. One strategy is to use bipolar tetraether lipids as a matrix of their plasma membranes, providing low ion permeabilities, even at high temperatures. Additionally, an inverted membrane potential can help to balance a large pH gradient of up to 4 at a proton motive force of delta p = 140-180 mV. This is not a general rule, because in several species the membrane potential contributes only minimally. Also, local buffering capacity and charge profiles across the membrane may significantly influence adaptation to bulk phase acidity. Neither complex I nor complex III electron transport-coupled proton pump equivalents have been found in aerobic archaea. Only terminal oxidases seem to provide either H+ pumping or the generation of a proton gradient by chemical charge separation. Organization, redox centres and primary structures of some archaeal terminal quinol oxidase complexes are known and will be discussed. Much less is known about anaerobic sulfur reducers. For those a possible mechanism for proton exclusion is proposed.
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PMID:How can archaea cope with extreme acidity? 1020 17

Active proton transfer through membrane proteins is accomplished by shifts in the acidity of internal amino acids, prosthetic groups, and water molecules. The recently introduced step-scan attenuated total reflection Fourier-transform infrared (ATR/FT-IR) spectroscopy was employed to determine transient pKa changes of single amino acid side chains of the proton pump bacteriorhodopsin. The high pKa of D96 (>12 in the ground state) drops to 7.1 +/- 0.2 (in 1 M KCl) during the lifetime of the N intermediate, quantitating the role of D96 as the internal proton donor of the retinal Schiff base. We conclude from experiments on the pH dependence of the proton release reaction and on point mutants where each of the glutamates on the extracellular surface has been exchanged that besides D85 no other carboxylic group changes its protonation state during proton release. However, E194 and E204 interact with D85, the primary proton acceptor of the Schiff base proton. The C==O stretching vibration of D85 undergoes a characteristic pH-dependent shift in frequency during the M state of wild-type bacteriorhodopsin with a pKa of 5.2 (+/-0.3) which is abolished in the single-site mutants E194Q and E204Q and the quadruple mutant E9Q/E74Q/E194Q/E204Q. The double mutation E9Q/E74Q does not affect the lifetime of the intermediates, ruling out any participation of these residues in the proton transfer chain of bacteriorhodopsin. This study demonstrates that transient changes in acidity of single amino acid residues can be quantified in situ with infrared spectroscopy.
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PMID:In situ determination of transient pKa changes of internal amino acids of bacteriorhodopsin by using time-resolved attenuated total reflection Fourier-transform infrared spectroscopy. 1031 12


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