Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.6.1.3 (ATPase)
 65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The influence of occupancy by ouabain of its specific binding site on the stability and conformation of the Na+/K+-ATPase has been investigated. When native Na+/K+-ATPase is exposed to guanidinium chloride or diluted acid, tryptophanyl fluorescence falls to 50% of the initial value. If ouabain is bound, higher concentrations of GdmCl or acidity are needed to reach the same decrease in fluorescence. The rotational diffusion coefficient (relaxation time), shows higher values for the Na+/K+-ATPase (ouabain) complex compared to the enzyme alone, suggesting an increase in molecular asymmetry. This observation is confirmed by the Stern-Volmer analysis that shows an increase in the accessibility of the fluorophores in the Na+/K+-ATPase (ouabain) (KSV = 15.6 M-1) with respect to the native enzyme (KSV = 12.5 M-1). Iodine perturbation of the enzyme labelled with FITC, demonstrates a decrease in the accessibility of the fluorescein probe in the Na+/K+-ATPase(ouabain) (KSV = 4 M-1) compared to the Na+/K+-ATPase (KSV = 7 M-1) indicating that after ouabain binding this site of the enzyme is less exposed to the solvent. These data, in agreement with other reports, suggest an allosteric effect of ouabain binding on the Na+/K+-ATPase conformation.
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PMID:Effect of ouabain binding on the fluorescent properties of the Na+/K+-ATPase. 284 33

Several divalent metal ions were used as kinetic probes of the beef heart mitochondrial adenosinetriphosphatase (F1) under a variety of conditions, and the relationship between the properties of the catalytic metal ion and the catalytic activity of the enzyme was examined. Vmax for ATP hydrolysis was largest when metal ions characterized by intermediate values of acidity of coordinated water molecules (pKa) and metal-nucleotide stability constants (Kstab) were present. As temperature increased, the peak of Vmax vs. pKa (or Kstab) shifted to lower initial values of pKa or Kstab. The solvent deuterium isotope effect on Vmax (DV) was normal and largest when the metal ion present during F1-catalyzed ATP hydrolysis was most acidic and the metal nucleotide stability constant was large. When an active site tyrosine on F1 was nitrated, Vmax was most affected when the metal ion present was least acidic and the metal nucleotide stability constant was small. The isotope effect on V/K (DV/K) was normal, small, and apparently independent of the metal ion present. ADP inhibition of F1-catalyzed ATP hydrolysis is competitive, and the Ki is independent of the metal ion present. The degree of Pi inhibition of F1 is dependent on the metal ion present. The inhibition by Pi is competitive at low temperature and becomes noncompetitive as temperature increases. These and previous results support a mechanism whereby a water molecule coordinated to the metal ion of an enzyme-bound gamma-monodentate metal-ATP complex is deprotonated to begin a series of events whereby a beta,gamma-bidentate metal-ATP complex is produced. Upon hydrolysis, the bond between the metal ion and the beta-phosphate of ADP in the Pi-metal-ADP complex is broken before products (ADP and metal-Pi) are released.
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PMID:Dependence of the activity of beef heart mitochondrial adenosinetriphosphatase on the properties of the catalytic metal ion. 288 48

Membranes from Halobacterium saccharovorum contained a cryptic ATPase which required Mg2+ or Mn2+ and was activated by Triton X-100. The optimal pH for ATP hydrolysis was 9-10. ATP or GTP were hydrolyzed at the same rate while ITP, CTP, and UTP were hydrolyzed at about half that rate. The products of ATP hydrolysis were ADP and phosphate. The ATPase required high concentrations (3.5 M) of NaCl for maximum activity. ADP was a competitive inhibitor of the activity, with an apparent Ki of 50 microM. Dicyclohexylcarbodiimide (DCCD) inhibited ATP hydrolysis. The inhibition was marginal at the optimum pH of the enzyme. When the ATPase was preincubated with DCCD at varying pH values, but assayed at the optimal pH for activity, DCCD inhibition was observed to increase with increasing acidity of the preincubation medium. DCCD inhibition was also dependent on time of preincubation, and protein and DCCD concentrations. When preincubated at pH 6.0 for 4 h at a protein:DCCD ratio of 40 (w/w), ATPase activity was inhibited 90%.
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PMID:Dicyclohexylcarbodiimide-sensitive ATPase in Halobacterium saccharovorum. 293 Oct 49

The toxicity of 31 phenols was studied by electro-rotation of yeast cells. Control yeast cells show both anti-field and co-field rotation, depending upon the field frequency applied. After treatment with supra-threshold amounts of phenols the anti-field rotation is weakened or abolished and a stronger co-field rotation can be seen. The proportion of cells showing the co-field rotation was found to be a sensitive measure of toxicity. Doses of 2.2 mumol/l of pentachlorophenol, or of 0.3 mumol/l of pentabromophenol were detectable after 3 h incubation at pH 4.0. At a given pH, the toxicity of the chlorophenols correlated extremely well with their octanol:water partition coefficients (Pow). The complete set of phenols showed fair overall correlation with Pow, but less good correlation with their acidity constants (pKa). In particular the toxicity of a given phenol was less than predicted from its pKa if the incubation pH was higher than the pKa. Biochemical assays on 23 of the phenols showed that the rotational sensitivity runs closely parallel to the sensitivities of cell growth rate and of the plasmamembrane ATPase, but less closely to the inhibition of purine incorporation. It appears that the electro-rotation method provides a useful and rapid test for the presence of organic ecotoxins. The test enables us to distinguish differences between single cells, and is comparable in sensitivity to biochemical tests that use vesicles or homogenates derived from a cell population.
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PMID:The comparative influence of substituted phenols (especially chlorophenols) on yeast cells assayed by electro-rotation and other methods. 296 20

Calciosomes are small cytoplasmic vacuoles identified in various nonmuscle cell types by their content of protein(s) similar to calsequestrin (CS), the Ca2+ storage protein of the muscle sarcoplasmic reticulum (SR). These entities have been interpreted as the "primitive" counterpart of the SR, and suggested to be the organelle target of inositol-1,4,5-triphosphate action (Volpe, P., K. H. Krause, S. Hashimoto, F. Zorzato, T. Pozzan, J. Meldolesi, and D. P. Lew. Proc. Natl. Acad. Sci. USA. 85:1091-1095). Immunoperoxidase and immunogold experiments carried out in both thick and ultrathin cryosections of rat hepatocytes and pancreatic acinar cells by using antimuscle CS antibodies revealed a specific labeling widely distributed in the entire cytoplasm, while nuclei were negative. Individual calciosomes appeared as small (105 nm) membrane-bound vacuoles intermingled with, and often apposed to ER cisternae and mitochondria. Other calciosomes were scattered in the Golgi area, in between zymogen granules and beneath the plasma membrane. The cumulative volume of the CS-positive organelles was measured to account for the 0.8 and 0.45% of the cytoplasm in liver and pancreas cells, respectively. The real total volume of the calciosome compartment is expected to be approximately twice as large. In hepatocytes, structures similar to CS-positive calciosomes were decorated by antibodies against the Ca2+ ATPase of muscle SR, while ER cisternae were not. By dual labeling, colocalization was revealed in 53.6% of the organelles, with 37.6% positive for the ATPase only. CS appeared preferentially confined to the content, and the Ca2+ ATPase to the contour of the organelle. The results suggested a partial segregation of the two antigens, reminiscent of their well-known segregation in muscle SR. Additional dual-label experiments demonstrated that hepatic calciosomes express neither two ER markers (cytochrome-P450 and NADH-cytochrome b5 reductase) nor the endolysosome marker, luminal acidity (revealed by 3-[2,4-dinitroanilino]-3'-amino-N-methyl dipropylamine). Calciosomes appear as unique cytological entities, ideally equipped to play a role in the rapid-scale control of the cytosolic-free Ca2+ in nonmuscle cells.
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PMID:Immunocytochemistry of calciosomes in liver and pancreas. 297 58

The acidity and lipophilicity of the fluorinated arylalkylsulphonamides are determined by the nature of the substituents on their aromatic rings. Herbicidal and anti-inflammatory effects of these compounds appear to increase with their lipophilicity. According to Mitchell's chemiosmotic theory, lipophilic weak-acid uncoupling agents act by transporting protons across the inner mitochondrial membrane and thus destroying the proton-electrochemical potential gradient required for ATP synthesis and ion transport. 1:1:1-Trifluoro-N-[2-methyl-4-(phenylsulphonyl) phenyl]methanesulphonamide (Perfluidone), a pre- and post-emergence herbicide (at 20 microM concentration), in isolated rat-liver mitochondria caused (1) a 2-fold stimulation of metabolic state-4 respiration, (2) a reduction of respiratory control ratio (RCR) by at least 50%, (3) an enhancement of latent ATPase activity by 40%, (4) a significant passive swelling of mitochondria in 0.15 N NH4Cl(delta A520 = -0.46 +/- 0.003), (5) proton intrusion during state-4 respiration (356 ng H+/min/mg protein; ng H+/min/mg protein with 5 microM perfluidone), and (6) at least 100% stimulation of oligomycin-inhibited respiration. These profiles are qualitatively comparable with those of the classical lipophilic weak-acid uncoupler, carbonylcyanide-trifluoro-methoxyphenylene hydrazone (FCCP), which acts by promoting the electrogenic transport of H+ ions across mitochondrial membrane.
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PMID:Protonophoric properties of fluorinated arylalkylsulfonamides. Observations with perfluidone. 299 24

The H+K+-ATPase is supposed to be the terminal step in the acid-secreting pathway in the parietal cell. Omeprazole blocks this enzyme, resulting in a marked inhibition of basal and stimulated acid secretion. With omeprazole 20 mg daily, 24-hour intragastric acidity is decreased by about 90%. Several clinical studies have now been published in which omeprazole has been compared with the H2-receptor antagonists cimetidine and ranitidine. Omeprazole in doses between 20 and 40 mg daily resulted in healing rates between 65% and 82% after treatment for 2 weeks and between 90% and 100% after treatment for 4 weeks. Treatment with omeprazole also gave faster and more pronounced pain relief. One comparative study in gastric ulcer has also been published showing healing rates equal to those with ranitidine. Placebo-controlled trials have also shown very pronounced therapeutic effect in reflux esophagitis. Omeprazole seems to be the drug of choice in Zollinger-Ellison syndrome, giving beneficial clinical effects and pronounced and long-lasting reduction in gastric acid secretion.
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PMID:Clinical perspectives of drugs inhibiting acid secretion--H+K+-ATPase inhibitors. 302 57

The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of omeprazole are reviewed. Omeprazole, a substituted benzimidazole, has a unique site and mechanism of action because it inhibits the proton pump--i.e., hydrogen, potassium adenosine triphosphatase (H+,K+-ATPase)--and consequently blocks the final common step in the gastric acid secretory pathway. Omeprazole inhibits basal and histamine-, gastrin- and pentagastrin-stimulated gastric hydrochloric acid secretion. It produces a dose-dependent reduction in gastric acidity, gastric acid output, and gastric juice volume and has variable effects on pepsin secretion. Omeprazole has no documented effect on esophageal motility or lower esophageal sphincter pressure. Omeprazole is variably absorbed from the gastrointestinal tract, and food appears to decrease the rate, but not the extent, of drug absorption. The drug is approximately 95% bound to plasma proteins and is metabolized to inactive components that are enterohepatically or renally eliminated. Omeprazole is more effective (in most studies) than H2-receptor antagonists in treating duodenal ulcer, at least as effective in treating benign gastric ulcer, and more effective in treating reflux esophagitis. Omeprazole has been used successfully in patients with Zollinger-Ellison syndrome refractory to treatment with H2-receptor antagonists. Gastrointestinal complaints (nausea and diarrhea) are the most commonly reported adverse effects associated with omeprazole therapy. The most frequently reported laboratory abnormality occurring with omeprazole use is elevation of serum aspartate aminotransferase and alanine aminotransferase concentrations. Omeprazole will serve a valuable role in the management of gastrointestinal tract ulcers and hypersecretory conditions.
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PMID:Therapeutic evaluation of omeprazole. 306 85

The effect of gastric anacidity on the absorption of food-bound cobalamins is uncertain. Omeprazole, an inhibitor of the enzyme H-K-ATPase in the parietal cell, is the most potent inhibitor of gastric acidity known so far. In 17 healthy male volunteers the absorption of liver-bound cobalamins was assessed after a single intravenous dose of omeprazole (80 mg) or placebo in a double-blind, crossover manner. The effect of omeprazole on pH, gastric acidity, and intrinsic factor (IF) concentration was measured in aspirates of gastric juice 5 min before and 30 and 60 min after the administration of liver homogenate containing 0.74 nmol of 57Co-labelled cobalamins. Omeprazole treatment resulted in anacidity (pH values above 6.0) in 14 individuals 30 min after the liver dose and in 15 individuals after 60 min. The IF concentration was unchanged in the omeprazole experiment as compared with the placebo experiment. The absorption of liver-bound cobalamins was 310 pmol (189-501 pmol) in the omeprazole experiment as compared with 415 pmol (150-549 pmol) in the placebo experiment (median values and range, p = 0.5228). We suggest that anacidity induced by omeprazole does not reduce the absorption of liver-bound cobalamins.
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PMID:The effect of omeprazole on gastric acidity and the absorption of liver cobalamins. 357 26

Gastric ulcerations induced in rats by a combination of indomethacin and cold-stress (5 +/- 1 degrees C) for 6 hr were more severe than those induced by indomethacin or cold-stress alone. The acidity of gastric juice was increased in rats treated with indomethacin plus cold-stressed. Histamine H2 receptor antagonists, (H+-K+) ATPase inhibitors and prostaglandins inhibited gastric ulcer formation in indomethacin plus cold-stress treated rats, whereas anticholinergics aggravated the ulceration. The indomethacin plus cold-stress induced acid secretion was inhibited by cimetidine and omeprazole in pylorus-ligated rats. Atropine had less effect on the increase in acidity than cimetidine and omeprazole. These findings indicate that the ulcer formation in indomethacin plus cold-stress treated rats is related the increased in acidity of gastric juice. This gastric ulcer model may be useful for evaluating antiulcer agents.
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PMID:Effects of indomethacin and cold-stress on gastric acid secretion and ulceration. The effects of anti-acid secretory agents in rats. 367 83


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