Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Uncouplers of oxidative phosphorylation in mitochondria inhibit the coupling between the electron transport and phosphorylation reactions and thus inhibit ATP synthesis without affecting the respiratory chain and ATP synthase (H(+)-ATPase). Miscellaneous compounds are known to be uncouplers, but weakly acidic uncouplers are representative because they show very potent activities. The most potent uncouplers discovered so far are the hindered phenol SF 6847, and hydrophobic salicylanilide S-13, which are active in vitro at concentrations in the 10 nM range. For induction of uncoupling, an acid dissociable group, bulky hydrophobic moiety and strong electron-withdrawing group are required. Weakly acidic uncouplers are considered to produce uncoupling by their protonophoric action in the H(+)-impermeable mitochondrial membrane. For exerting these effects, the stability of the respective uncoupler anions in the hydrophobic membrane is very important. High stability is achieved by delocalization of the polar ionic charge through uncoupler (chemical)-specific mechanisms. Such an action of weakly acidic uncouplers is characteristic of the highly efficient membrane targeting action of a nonsite-specific type of bioactive compound.
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PMID:Uncouplers of oxidative phosphorylation. 217 86

The Na+/K+-ATPase of Chinese Hamster Ovary (CHO) cells, a plasma membrane bound protein was used as a test system to evaluate the toxicity of several phenol derivatives on membranes. Taking only 2 physico-chemical parameters into consideration, viz., the logarithm of the octanol/water partition coefficient as an indicator for the lipophilicity and the sigma-Hammett constant as a measure for the polarity of the phenol substitutes, it was possible to predict the toxicity with high significance. A multivariate regression analysis calculated a correlation coefficient of 0.99. The results confirm studies performed in our laboratory on cytotoxicity and on functional membrane proteins of fungal and mammalian cells [1,2], suggesting a common mechanism of toxicity by the action of hydrophobic xenobiotics on biomembranes. Taking into account the different sensitivities of the test systems, Quantitative Structure-Activity Relationship (QSAR) analyses could help to explain the basic toxicity of several classes of environmental chemicals.
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PMID:Correlation between the lipophilicity of substituted phenols and their inhibition of the Na+/K+-ATPase of Chinese hamster ovary cells. 255 18

Bis(2-hydroxy-3-tert-butyl-5-methylphenyl)methane (bis-phenol) is the most potent inhibitor of the (Ca2+ + Mg2+)-ATPase of skeletal muscle sarcoplasmic reticulum yet identified. The compound behaves as a reversible, tight-binding inhibitor with apparent Ki = 0.3 microM. Butylated hydroxytoluene, butylated hydroxyanisole, and 4-nonylphenol are also effective inhibitors. These observations are of particular interest in light of the widespread use of such phenolic antioxidants and stabilizers in the food industry and in the manufacture of rubbers and plastics and the ease with which the compounds are extracted into organic solvents.
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PMID:Phenolic antioxidants: potent inhibitors of the (Ca2+ + Mg2+)-ATPase of sarcoplasmic reticulum. 294 19

A model of nonischemic hypoxia of the jejunum was designed in dogs, by shunting of blood from the inferior vena cava directly into the regional mesenteric arterial supply, thereby lowering the PaO2 of the blood that reached the jejunal wall from 98.6 +/- 3 to 62 +/- 5 mm Hg. Absorption rates of sodium, glucose, fructose, glycine, and the dibasic aminoacid lysine were studied by in situ luminal perfusion of a 30-cm proximal jejunal segment with a bicarbonate buffer solution containing phenol red as a nonabsorbable marker for determination of water fluxes. During periods of control, hypoxia, and after discontinuation of the venoarterial admixture (recovery), effluent perfusate was collected and mucosal biopsies were obtained for assay of lactase, maltase and sucrase activity, mucosal ATPase activity and ATP content, and for light- and electron microscopic examination. Mesenteric supply with hypoxic blood was associated with a significant inhibition of Na+,K+-ATPase activity (p less than 0.001) and a rise in mucosal ATP content (p less than 0.05). There was a significant reduction in the absorption rates of sodium (p less than 0.001), glucose, and glycine (p less than 0.01), but no change in the transport of fructose and of lysine. Brush border enzymes were unaltered. The histological appearance of the mucosa remained normal throughout the experiment, but on electron microscopy a distinct swelling of the enterocyte mitochondria was noted during the hypoxia period.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of nonischemic hypoxia on jejunal mucosal structure and function: study of an experimental model in dogs. 294 46

The in vitro effects of phenol and p-halogenated phenols on mitochondrial energy transfer reactions were examined using isolated rat liver mitochondria. The relationship between physiochemical properties of phenolic compounds and their effects on mitochondria were studied. Phenol and p-halogenated phenols induced the release of K+ ions from mitochondria, suggesting a change in permeability to K+ ions. A decrease in the respiratory control index, an increase in K+ release and stimulation of latent ATPase activity were observed with these compounds in the descending order of p-iodophenol, p-bromophenol, p-chlorophenol, p-fluorophenol and phenol. The concentrations of the phenolic compounds resulting in fifty percent inhibition of the respiratory control index and those resulting in fifty percent release of K+ ions significantly correlated with Hammett's substituent constant (sigma) and the hydrophobic binding constant (pi) of the compounds.
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PMID:Effect of phenol and halogenated phenols on energy transfer reactions of rat liver mitochondria. 296 43

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

Experimental data are presented concerning inhibition of Na, K-ATPase in rat heart sarcolemmal and rat brain synaptosomal membranes upon generation of activated oxygen species. It is shown that the activity of Na, K-ATPase is inhibited in membranes of both types during incubation with Fe2+ + ascorbate system, which generates O2 and OH- radicals and thus induces lipid peroxidation. The inhibitory effect is linearly dependent on the amount of the lipid peroxidation products (malondialdehyde) accumulated. Exogenous unsaturated phosphatidylethanolamine, when added to partially inactivated enzyme, does not produce reactivation of Na, K-ATPase. Free radical scavenger 4-methyl-2,6-di-(tertbutyl) phenol exerts both inhibition of lipid peroxidation and protection of Na, K-ATPase. Mg-ATPase is resistant to the action of lipid peroxidation inducing system. Bubbling of oxygen through membrane suspension results in no malondialdehyde accumulation, but is accompanied by Na, K-ATPase inhibition, which could not be prevented by free radical scavengers. It is suggested that generation of activated oxygen species results in oxidation of one of the essential amino acid residues in the active site of the enzyme.
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PMID:Mode of lipid peroxidation-induced inhibition of Na, K-ATPase. 299 67

Prostaglandin (PG) synthesis from [1-14C]-arachidonic acid by bovine dental pulp microsomes was stimulated by 0.1-0.5 mM concentrations of p-chlorophenol (PCP) and inhibited by more than 3 mM. Dual effects (stimulation and inhibition) of phenol, PCP, o-, m-, p- and tri-cresol on PG synthesis by rabbit kidney medullary microsomes were observed. Of various compounds tested, eugenol, thymol and guaiacol were the most potent inhibitors; the inhibitory action was reversible. Phenolic compounds did not affect the activity of glucose-6-phosphatase, adenosine triphosphatase, or lactate dehydrogenase in rabbit kidney medulla within the range of concentrations that stimulated or inhibited PG synthesis. Thus the analgesic effect of phenolic medicaments in endodontic therapy may be due to inhibition of arachidonic-acid metabolism.
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PMID:Effects of phenolic dental medicaments on prostaglandin synthesis by microsomes of bovine tooth pulp and rabbit kidney medulla. 325 25

A microsomal adenosine triphosphatase (ATPase) that requires both sodium and potassium ions is thought to be identical with, or an integral part of, the active cation transport system located in cell membranes. Attempts to isolate and purify (Na(+) + K(+))-ATPase have met with limited success because solubilization of microsomal protein causes partial, if not complete, loss of enzymatic activity. We now report the isolation from rat kidney microsomes of proteins which, though enzymatically inactive, could still be identified as components of the (Na(+) + K(+))-ATPase system. Phosphoproteins known to be intermediates in the hydrolysis of ATP by (Na(+) + K(+))-ATPase were prepared by incubating rat kidney microsomes with gamma-labeled ATP(33) in the presence of sodium or with P(32)-orthophosphate in the presence of ouabain. After the P(32)- and P(33)-labeled microsomes had been dissolved in phenol-acetic acid-urea, the resultant solutions were mixed and subjected to polyacrylamide gel electrophoresis. The radioactivity from both phosphorus isotopes was found almost exclusively in one of the resultant 21 protein bands. In contrast, the radioactive protein from DFP(32)-labeled microsomes moved slightly faster than the radioactive protein from microsomes labeled with P(33)-orthophosphate in the presence of ouabain. DFP inhibits (Na(+) + K(+))-ATPase by reacting with a nucleophilic site at or near the active site. These results suggest that while a single protein component of (Na(+) + K(+))-ATPase accepts the terminal phosphate from ATP, the final splitting of this phosphoprotein intermediate may be catalyzed by nucleophilic sites on a second protein.
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PMID:Identification of components of (Na+ plus K+)-adenosine triphosphatase by double isotopic labeling and electrophoresis. 424 29

Washed membranes of bovine adrenal chromaffin granules contained most of the cholesterol and phospholipids of the particle and 22% of the total protein. The protein/lipid ratio was about 0.45 (w/w). Dopamine(3,4-dihydroxyphenethylamine)beta-hydroxylase, Mg(2+)-activated nucleoside triphosphatase and cytochrome b-559 activities were present in the membrane. ATP was the best substrate for the nucleoside triphosphatase, whose pH optimum was 6.4, K(m) 7x10(-4)m and V(max.) 1.8mumol/h per mg of protein. Treatment of the membranes with various detergents caused a preferential solubilization of protein compared with lipids. Membranes dissolved in sodium dodecyl sulphate or phenol-acetic acid-urea were subjected to polyacrylamide-gel electrophoresis at alkaline and acid pH respectively. The electrophoretic patterns given by the proteins of the chromaffin granule membrane were distinct from those given by the chromogranins, and from those given by mitochondrial and microsomal membrane proteins.
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PMID:Membranes of the adrenal medulla. Behaviour of insoluble proteins of chromaffin granules on gel electrophoresis. 432 Aug 20


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