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)

This is a review article on newly developed antisecretory drugs which are now called proton pump inhibitors. Gastric H+ is secreted from the secretory membrane of parietal cells into the lumen of the stomach, using energy obtained by destructing ATP with H+, K+-ATPase (proton pump). Various substituted benzimidazoles such as timoprazole, picoprazole, omeprazole, or NC-1300 potently inhibits this proton pump at pH 6.0, thereby resulting in a strong inhibition of gastric H+ secretion. This inhibition of H+ secretion lasts for a long period, ie, 1-3 days after a single oral or intraduodenal administration, both in experimental animals and humans. This long lasting activity of these compounds appears to be due to their accumulation in the parietal cells because of their low pKa values (about 4.0). Proton pump inhibitors dose-dependently inhibit the development of various experimental ulcers and accelerate healing of chronic gastric ulcers in animals. Since these compounds also potently inhibit the development of HCl X ethanol or HCl X aspirin-induced gastric ulcers in animals, they are considered to have a cytoprotective activity. Some of the compounds (e.g., omeprazole) afforded a complete healing of peptic ulcers in man when it was given once daily for 2 to 4 weeks, without any adverse effects. Therefore, these proton pump inhibitors appear to be promising drugs for the treatment of peptic ulcer diseases.
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PMID:[Effects of gastric proton pump inhibitors on gastric secretion and peptic ulcers]. 287 85

In plant cells, transient changes in cytoplasmic Ca2+ levels can modulate numerous developmental processes. Ca2+ is accumulated in the vacuole via a H+/Ca2+ antiport system that is energized by the tonoplast H+-pumping ATPase. Inositol 1,4,5-triphosphate (InsP3), but not inositol 1,4-bisphosphate, myo-inositol 1-phosphate, or fructose 2,6-bisphosphate, caused a transient reduction of Ca2+ levels in tonoplast vesicles. The decrease was dependent on InsP3 concentration (Km apparent = 0.6 microM). The InsP3-induced Ca2+ release was blocked by the Ca2+ antagonist, 8-(N,N-diethylamino)-octyl 3,4,5-trimethoxybenzoate-HCl. These results suggest that the vacuolar membrane is one target site for InsP3 action and that InsP3 may operate as a second messenger in the mobilization of intracellular Ca2+ in plant cells.
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PMID:Inositol 1,4,5-trisphosphate releases Ca2+ from vacuolar membrane vesicles of oat roots. 288 29

The mechanism of stimulatory action of histamine on gastric alkaline secretion was investigated in anesthetized rats. Intravenous infusion of histamine (2-8 mg/kg/hr) dose-dependently stimulated acid secretion and in the presence of omeprazole (60 mg/kg), an H+/K+-adenosine triphosphatase inhibitor, produced an increase of gastric but not duodenal alkaline secretion; the degree of gastric alkalinization was also dependent on the dose of histamine, reaching the maximal values of approximately 1.0 microEq/10 min. Cimetidine (100 mg/kg s.c.) significantly inhibited both acid and alkaline secretory responses caused by histamine, whereas indomethacin (5 mg/kg s.c.) significantly prevented the increased alkaline secretion caused by histamine as well as mucosal acidification (100 mM HCl for 10 min). Tripelennamine (10 mg/kg s.c.) had no effect on either acid or alkaline secretion. Histamine (8 mg/kg/hr) reduced the arterial blood pressure (25.3%) and increased the mucosal vascular permeability in the stomach as determined by Evans blue (160%), but these vascular responses were significantly prevented only by tripelennamine, excluding the possible contribution of the vascular effects to the increased gastric alkaline secretion. These results suggest that histamine may stimulate gastric alkaline secretion as well as acid secretion, and the mechanism of histamine-induced alkaline secretion may involve both endogenous prostaglandins and stimulation of H2-receptors.
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PMID:Stimulation of gastric alkaline secretion by histamine in rats: possible involvement of histamine H2-receptors and endogenous prostaglandins. 291 81

Ca2+ ATPase molecules in sarcoplasmic reticulum, isolated from rabbit skeletal muscle, have been induced to crystallize into two-dimensional arrays by incubating the vesicles with phospholipase A2 and dialysing against dilute Tris/HCl buffer. These crystals differ in shape and size from those produced by treatment of the sarcoplasmic reticulum vesicles with Na3VO4. However, the unit-cell dimensions of both types of crystals are similar. The differences in shape and size are presumably due to differences in the mechanisms of crystal formation induced by treatment with phospholipase and Na3VO4.
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PMID:Crystallization of Ca2+ ATPase in sarcoplasmic reticulum vesicles by phospholipase treatment. 293 Nov 37

The Malachite Green method for determination of inorganic phosphate (Pi) (Itaya K. & Ui, M. (1966) Clin. Chim. Acta 14, 361-366) was modified to measure Pi in the range of 0.2-15 nmol per ml of ATPase reaction mixture. An ATPase reaction mixture is quenched with an equal volume of 0.6 M PCA; the supernatant after centrifugation is mixed with an equal volume of the Malachite Green/molybdate reagent containing 2 g of sodium molybdate, 0.3 g of Malachite Green and 0.5 g of Triton X-100 or Sterox SE in 1 liter of 0.7 M HCl, and the absorbance at 650 nm is then measured after a 35-40 min incubation at 25 degrees C. Owing to the high sensitivity and simplicity of the modified method, the slow time course of myosin ATP hydrolysis in the presence of Mg2+ and the size of initial phosphate burst can be determined accurately using relatively low concentrations of native myosin and its subfragment-1. The phosphate burst size varied with changes in pH, ionic strength, and temperature. A typical value was 0.8-0.9 mol per site in 0.1 M KCl, 10 mM MgCl2, pH 8.0 at 25 degrees C for fresh enzyme preparations.
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PMID:The initial phosphate burst in ATP hydrolysis by myosin and subfragment-1 as studied by a modified malachite green method for determination of inorganic phosphate. 294 Feb 37

Dynein 1 was extracted from sperm flagella of the sea urchin Tripneustes gratilla with 0.6 M NaCl and dialyzed against 0.5 mM EDTA, 14 mM 2-mercaptoethanol, 5 mM imidazole/HCl buffer, pH 7.0, for 24-48 h. In some cases, fractions containing the alpha heavy chain and the beta/intermediate chain 1 complex (beta/IC1) were separated by density gradient centrifugation in the same solution. Treatment of the samples at a trypsin:protein ratio of 1:10 w/w for 32 min at room temperature yields a crude digest from which Fragment A is purified by density gradient centrifugation. The purified Fragment A consists of two principal peptides (Mr = 195,000 and 130,000) that cosediment with the peak of ATPase activity at 12.5 S, which is slightly faster than the 11 S of the original beta/IC1 complex. When digests of the separated alpha chain and of the beta/IC1 complex are followed as a function of time, the early cleavages of the two heavy chains (Mr = 428,000) resemble each other in that both lead to similarly sized peptides of Mr 316,000 and 296,000, but only in the beta/IC1 fraction does the digestion proceed to form Fragment A. The remainder of the beta chain, termed Fragment B, occurs as an Mr 110,000 peptide sedimenting at 5.7 S with no associated ATPase activity. Fragment A has a specific ATPase activity of 4.3 mumol Pi X min-1 X mg-1, with a Km of 29 microM in 0.1 M NaCl medium, and an apparent Ki for inhibition by vanadate of 1.2 microM in the absence of salt, and 22 microM in 0.6 M NaCl. Photoaffinity labeling with [alpha-32P]8-azidoadenosine 5'-triphosphate indicates that the ATP binding site on the beta chain of dynein 1 is located on the Mr 195,000 peptide of Fragment A. The possibility that Fragments A and B of the beta/IC1 complex may correspond to the head and tail regions of the tadpole-shaped particle seen by electron microscopy is discussed.
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PMID:Tryptic digestion of dynein 1 in low salt medium. Origin and properties of fragment A. 295 97

The Na+,K+-ATPase activity of human leucocytes was assayed by measuring the release of inorganic phosphate (Pi) from ATP. The maximum enzyme activity was achieved under the following conditions: concentration (mmol/l), Tris/HCl 50, Na 100, K 15, ATP 5, Mg 7, EDTA 1; pH 7.2 and temperature 37 degrees C, were optimal. Ouabain showed maximal inhibition at a concentration of 10-100 mumol/l. Ethanol, the solvent for ouabain, had a dose-related inhibitory effect. Heparin or citrate used as an anticoagulant gave similar results. Leucocyte samples could be stored at -20 degrees C for up to 6 days without loss of activity. Hypotonic lysis had advantages over sonication as the technique for cell disruption. The leucocyte Na+,K+-ATPase enzyme activity in healthy subjects was 186 mumol of Pi h-1g-1 of protein (median) with a range 136-243 mumol of Pi h-1g-1 of protein. The within-batch coefficient of variation was 6.4% and the between-batch precision was 9.6%.
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PMID:Optimal conditions for measurement of Na+,K+-ATPase activity of human leucocytes. 298 51

ATP and GTP have been compared as substrates for (Na+ + K+)-ATPase in Na+-activated hydrolysis, Na+-activated phosphorylation, and the E2K----E1K transition. Without added K+ the optimal Na+-activated hydrolysis rates in imidazole-HCl (pH 7.2) are equal, but are reached at different Na+ concentrations: 80 mM Na+ for GTP, 300 mM Na+ for ATP. The affinities of the substrates for the enzyme are widely different: Km for ATP 0.6 microM, for GTP 147 microM. The Mg-complexed nucleotides antagonize activation as well as inhibition by Na+, depending on the affinity and concentration of the substrate. The optimal 3-s phosphorylation levels in imidazole-HCl (pH 7.0) are equally high for the two substrates (3.6 nmol/mg protein). The Km value for ATP is 0.1-0.2 microM and for GTP it ranges from 50 to 170 microM, depending on the Na+ concentration. The affinity of Na+ for the enzyme in phosphorylation is lower with the lower affinity substrate: Km (Na+) is 1.1 mM with ATP and 3.6 mM with GTP. The GTP-phosphorylated intermediate exists, like the ATP-phosphorylated intermediate, in the E2P conformation. Addition of K+ increases the optimal hydrolytic activity 30-fold for ATP (at 100 mM Na+ + 10 mM K+) and 2-fold for GTP (at 100 mM Na+ + 0.16 mM K+). K+ greatly increases the Km values for both substrates (to 430 microM for ATP and 320 microM for GTP). Above 0.16 mM K+ inhibits GTP hydrolysis. GTP does not reverse the quenching effect of K+ on the fluorescence of the 5-iodoacetamidofluorescein-labeled enzyme. ATP fully reverses this effect, which represents the transition from E1K to E2K. Hence GTP is unable to drive the E2K----E1K transition.
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PMID:The locus of nucleotide specificity in the reaction mechanism of (Na+ + K+)-ATPase determined with ATP and GTP as substrates. 298 22

Gastric mucosal damage was produced in rats after pyloric ligation by intragastric administration of 200 mg/kg aspirin diluted in 2 ml 150 mmol/l HCl. The animals in the control group received 2 ml saline solution, or submitted to pyloric ligation only. The animals were killed 4 h after the pyloric ligation, when the number and severity of gastric lesions (ulcers), and the gastric fundic mucosal level of adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), cyclic adenosine monophosphate (cAMP) and lactate, were noted and measured. The adenylate pool (ATP + ADP + AMP) and the energy charge (ATP + 0.5ADP). (ATP + ADP + AMP)-1 were calculated. It was found that: the gastric H+ output decreased significantly in the pylorus-ligated plus aspirin-treated animals; the number and severity of gastric lesions increased significantly in the pylorus-ligated aspirin-treated animals; the extent of ATP transformation into the ADP decreased significantly in the pylorus-ligated aspirin-treated animals; the extent of ATP transformation into the cAMP decreased significantly during the aspirin treatment; the values of adenylate pool and of "energy charge" remained unchanged in the different groups of animals. It is concluded that: the decreased H+ output in the pylorus-ligated plus aspirin-treated group can be obtained by the decreased extent of ATP transformation into the ADP by membrane ATPase, and the biochemical changes in the gastric mucosa indicate a decreased energy turnover.
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PMID:Biochemical background of the development of gastric mucosal damage in pylorus-ligated plus aspirin-treated rats. 300 88

The reasons for differences in the Na,K-ATPase activity in rat erythrocyte ghosts obtained by hypoosmotic hemolysis in 10 mM Tris-HCl buffer pH 7.6 in the absence ("Tris-ghosts") and presence ("EDTA-ghosts") were investigated. Structurally different detergents (Triton X-100, Tween-20 and sodium deoxycholate) taken at optimal concentrations increased the enzyme activity in a similar way, i. e., 4-fold in "Tris-ghost" and by 30% in "EDTA-ghosts", the absolute activity of Na,K-ATPase in both preparations being levelled out. In the absence of EDTA, only 50-60% of the maximal enzyme activity could be revealed. Thus, in non-nuclear erythrocyte ghosts the maximal Na,K-ATPase activity can be revealed only upon a combined use of a detergent and chelator. It is concluded that the activating effect of the detergents consisting in the increase of the membrane permeability is realized on the outer surface of the membrane, whereas that of EDTA is localized on its inner surface, which is probably due to the disintegration of the cytoskeleton as a result of attachment of membrane-bound Ca2+.
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PMID:[Mechanism of the activating effect of detergents and chelating agents on the Na, K-ATPase activity of erythrocyte ghosts]. 300 61


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