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)

Fluoride ions inhibit several membrane enzymes in a manner that is dependent on membrane fluidity. Inhibition of (Na+, K+)-ATPase by fluoride ions may be a model for membrane effects on (Na+, K+)-ATPase. Therefore, we have examined properties of fluoride inhibition relative to interactions with ethanol and to ligands that alter sensitivity of (Na+, K+)-ATPase to ethanol. Fluoride ion reduced the K0.5 and Hill coefficient for K+ activation of p-nitrophenylphosphatase. Ethanol decreased the Hill coefficient and apparent affinity for inhibition of phosphatase activity by fluoride ion while dimethylsulfoxide had the opposite effects. Chronic ethanol treatment in vivo, which produced behavioral tolerance, had effects on fluoride inhibition opposite to those of ethanol in vitro. Inhibition by fluoride therefore may provide a useful marker for physiologic or pharmacologic conditions that alter regulation of (Na+, K+)-ATPase by membrane properties.
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PMID:Inhibition of (Na+, K+)-ATPase by fluoride: evidence for a membrane adaptation to ethanol. 215 28

We investigated interactions between ethanol and active cation transport mediated by Na,K-ATPase in rat brain synaptoneurosomes. Conditions that increased internal sodium also increased sensitivity of transport to ethanol, whereas low-sodium medium had the opposite effect. Ethanol also blocked the stimulation of ouabain-sensitive transport, glucose uptake and hyperpolarization associated with sodium influx. Low calcium decreased, while the calcium ionophore A23187 increased, sensitivity to ethanol. Inhibition of mitochondrial respiration or incubation under anaerobic conditions increased sensitivity of transport to inhibition by ethanol, but did not prevent the effect of A23187. Consistent with increased sensitivity to ethanol by cell calcium, ethanol potentiated the inhibition of transport by A23187. Although transport under basal conditions does not appear very sensitive to ethanol, these data suggest that sensitivity to ethanol may be increased under conditions associated with increased neural activity, and that ethanol may reduce the transport response to electrical activity.
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PMID:Ethanol inhibition of active 86Rb(+)-transport: evidence for enhancement by sodium or calcium influx. 216 86

A central belief about ethanol is that it acts mainly by partitioning into the lipid bilayer of membranes. Newer ideas focus on the neuronal synapse and suggest that ethanol can allosterically change protein conformation, as is suggested by studies on GABA-receptor-mediated chloride uptake and on (Na(+)-K+)-ATPase. Several studies from my laboratory suggest that ethanol enhances enzymatic cleavage of sialic acid (SA) from gangliosides, and perhaps also glycoproteins, but does so without stimulating enzyme activity, suggesting conformational changes that affect accessibility. I propose a new model for the cell membrane in the synaptic region, which features gangliosides surrounding membrane proteins, with an interspersed film of water creating hydrogen bonds that anchor SA moieties to membrane protein. I believe that we should consider the possibility that an important action of ethanol, and polar anesthetics, is due to hydrophilic, not hydrophobic, properties and the ability to dehydrate the cell-surface microdomain. Our laboratory has recently advanced the theory that ethanol dehydrates a "solvent regulatory site" of membrane (Na(+)-K+)-ATPase. This principle might be extended to other enzymes and receptor proteins, as well as to the accessibility of sialoglycoconjugates to sialidase (neuraminidase). Hydrogen bonding between SA and polar regions of receptor protein, and the conformation on both imposed by it, would surely be changed by minor degrees of dehydration and substitution of alcohol molecules for water. Ethanol, unlike water, can only hydrogen bond "at one end." Displacement of water by ethanol would not only "free" the SA groups and make them more vulnerable to enzymatic cleavage but also could simultaneously change the conformation of receptor protein. Similarly, ethanol may displace water that links the polar heads of phospholipids to polar portions of receptors proteins. Ethanol may have an even more important and direct effect of substituting for hydrogen-bonded water within protein itself.
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PMID:Dehydration: a new alcohol theory. 217 30

Using isolated healthy human leucocytes and erythrocytes as model cells, we investigated the inhibitory effect of ethanol, its metabolites and of other toxic alcohols on the active fluxes of rubidium (Rb: equivalent to K) and sodium (Na), and on Na,K-ATPase activity. Ethanol (80 mmol X l-1) inhibited total and ouabain-sensitive 86Rb influx and 22Na efflux in leucocytes, this being dose-related for total, ouabain-sensitive and ouabain-insensitive fluxes at higher concentrations. In erythrocytes inhibition occurred at 20 mmol X l-1 for 86Rb influx, dose-related at higher concentrations as for leucocytes. 22Na efflux was inhibited at 80 mmol X l-1 and above. Acetaldehyde (0.1 and 0.2 mmol X l-1), 1,2-propanediol (0.8 mmol X l-1) and 2,3-butanediol (0.4 mmol X l-1) inhibited all fractions of 86Rb influx in erythrocytes, but not in leucocytes. Methanol, 2-propanol and 1,2-ethanediol (16 and 32 mmol X l-1) inhibited 86Rb influx in erythrocytes, but not in leucocytes. The order of potency was 2-propanol greater than 1,2-ethanediol greater than methanol. Na,K-ATPase activity was inhibited in lysed leucocyte and erythrocyte preparations only at very high concentrations of the alcohols--suggesting that inhibition is due to an alteration in membrane structure and not to a direct effect on the enzyme.
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PMID:The acute in vitro effect of ethanol, its metabolites and other toxic alcohols on ion flux in isolated human leucocytes and erythrocytes. 242 65

Ethanol, in vitro, decreases muscle fiber twitch tension by a mechanism unrelated to the electrical events of the motor end-plate or muscle surface membranes, an effect which may be attributable to a primary ethanol effect on the calcium release process of the sarcoplasmic reticulum. In this study, ethanol was found to progressively decrease a form of calcium release from isolated sarcoplasmic reticulum vesicles seen after calcium loading in high-phosphate media (spontaneous calcium release). Elevated extravesicular free calcium concentrations are known to inhibit spontaneous calcium release, and the ability of sarcoplasmic reticulum to achieve and maintain submicromolar extravesicular free calcium concentrations in the presence of ethanol was therefore determined. Ethanol had no effect on the low extravesicular free calcium concentrations achieved by isolated sarcoplasmic reticulum, and had no effect on residual ATPase activity remaining after cessation of calcium pumping. This latter result suggests that efflux of vesicular calcium and persistent calcium reaccumulation do not occur in the presence of ethanol. These results suggest that ethanol-induced depression of spontaneous calcium release is not attributable to ethanol effects on sarcoplasmic reticulum membrane calcium leakage or on sarcoplasmic reticulum calcium pumping. Ethanol inhibition of spontaneous calcium release from isolated sarcopasmic reticulum may reflect an effect of ethanol on the calcium release process in intact muscle fibers responsible for ethanol-induced decreases in muscle fiber twitch tension.
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PMID:Ethanol inhibition of spontaneous calcium release from isolated sarcoplasmic reticulum. 253 74

In the present work we have analyzed the effect of prenatal ethanol exposure on the activity of several glial marker and functional enzymes during the development of astrocytes isolated from rat brain as well as in primary culture. The activity of marker enzymes glutamine synthetase and butylcholinesterase showed no differences between isolated astrocytes from 15 and 70 day old control rats. However, the activity of the membrane-bound enzymes (Na+K)ATPase and 5'-nucleotidase was higher in astrocytes from 70 day old control rats than in those from 15 day old animals. Although the pattern found in astrocytes from alcohol-exposed rats was similar to that of controls, the levels of activity of the enzymes were lower in alcoholic than in control animals. When control astrocytes in primary culture were used, the activity of (Na+K)ATPase and 5'-nucleotidase increased throughout the entire culture period. In contrast, the maximal activity of glutamine synthetase was found at 7 days of culture. Ethanol also induced a decrease in the activity of all enzymes, which was more evident at the end of the culture period. These results indicate that the activity of the enzyme markers analyzed increased mainly during the first weeks of life and remained constant after this period. By contrast, the membrane-bound enzymes studied showed a progressive increase with age. In conclusion, since these astrocyte enzymes are important in the regulation of several neuronal functions through the control of the composition of extracellular fluid, the effect of ethanol on their activities could explain some of the neuronal alterations reported in children and animals exposed to ethanol during development.
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PMID:Effect of prenatal exposure to alcohol on membrane-bound enzymes during astrocyte development in vivo and in primary culture. 257 55

We have characterized the interactive effects of ethanol and dimethylsulfoxide on synaptosomal uptakes of gamma-aminobutyric acid (GABA) and choline. Ethanol is a membrane-disordering agent which has been shown to inhibit synaptosomal high-affinity choline uptake at pharmacologically relevant ethanol concentrations, and to inhibit synaptosomal GABA uptake at higher ethanol concentrations. Dimethylsulfoxide (DMSO) is an organic solvent which has been shown to have a stabilizing effect on artificial phospholipid bilayers, and to have effects on conformation of and cation binding to brain (Na+, K+)-ATPase which are opposite those of ethanol. DMSO alone (2-10% v/v) inhibited synaptosomal uptakes of GABA and of choline in a concentration-dependent fashion, with choline uptake inhibited to a greater degree than GABA uptake. This result is qualitatively similar to the effects of ethanol on these uptake processes. DMSO at low concentrations (0.3-1.5% v/v) had no effect on inhibition of GABA and choline uptake by 0.6 M ethanol, and higher DMSO concentrations resulted only in further inhibition. Similarly, ethanol (0.3 M) had no effect on inhibition of GABA and choline uptake by 5% (v/v) DMSO, and higher ethanol concentrations (0.6-1.2 M) resulted only in further inhibition. We conclude that the inhibiting effects of ethanol on synaptosomal GABA and choline uptake are not reversed by DMSO.
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PMID:Synaptosomal uptake of choline and of gamma-aminobutyric acid: effects of ethanol and of dimethylsulfoxide. 262 18

The role of lipids in the effect of ethanol on synaptosomal (Na + K)ATPase was studied using native and partially delipidized synaptosomal membranes from control and alcoholic rats. A biphasic effect of alcohol was observed with the (N + K)ATPase from control membranes. Ethanol at low concentrations (less than 100 mM) appears to enhance the enzyme activity, but at higher concentrations (greater than 300 mM) was inhibitory. The biphasic response to ethanol was also observed with the (Na + K)ATPase isolated from alcoholic animals; however, in this case the enzyme showed a resistance to the inhibitory effect of ethanol. Delipidization of synaptic membranes with Lubrol WX or phospholipase A practically abolishes the effects of alcohol on (Na + K)ATPase from both control and alcoholic animals. It thus seems that the effects of ethanol are due mainly to their interaction with the lipids surrounding the enzyme. Furthermore, addition of ethanol to native membranes did not change the Vmax and Km for K+. However, when ethanol at the same concentration was added to delipidized membranes, a decrease in Km with no change in Vmax was observed. Ethanol under these conditions apparently interacts also with the enzyme protein. On the other hand, chronic ethanol intake produces an increase of both Vmax and Km for K+. However, when alcohol was added in vitro, there were no changes in the kinetic parameters of either native or delipidized membranes. These data indicate that although the effects of ethanol on synaptosomal (Na + K)ATPase are mainly due to its interaction with the lipid microenvironment of the enzyme, a direct ethanol action on the enzyme protein also occurs. Our data further suggest that chronic ethanol treatment alters enzyme sensitivity to the effect of ethanol which may be related to the membrane-lipid composition and/or to changes in the conformation of the enzyme protein.
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PMID:Effects of ethanol on rat brain (Na + K)ATPase from native and delipidized synaptic membranes. 282 18

The effects of ethanol at concentrations below 10% on the conformation of tropomyosin, its end-to-end polymerization, its binding to F-actin, and its effects on actomyosin ATPase activity were studied. Ethanol stabilized the tropomyosin conformation by shifting the helix thermal unfolding profile to higher temperatures, and increased the end-to-end polymerization of tropomyosin. Ethanol-induced changes in the excimer fluorescence of pyrene-tropomyosin indicated that its conformation was stabilized by ethanol both free and bound to F-actin. Effects of tropomyosin and tropomyosin-troponin on actomyosin ATPase activity were measured under conditions for which tropomyosin binding to F-actin increases the activity. Under conditions for which the binding of tropomyosin to F-actin is optimum, in the presence of tropomyosin, the actomyosin ATPase activity decreased as the ethanol concentration increased, further indicating that ethanol induces a structural change in the tropomyosin-F-actin complex. Under conditions for which the binding of tropomyosin to F-actin is weak (low salt or high temperature), addition of ethanol increased the ATPase activity due to increased binding of tropomyosin to F-actin. Thus, ethanol appears to modify actomyosin ATPase activity by increasing the binding of tropomyosin to F-actin and affecting the structure of tropomyosin in the tropomyosin-F-actin filament.
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PMID:Effect of ethanol on tropomyosin in solution and in reconstituted thin filaments. 293

The effect of ethanol on the transport of organic ions in rabbit kidney cortical slices was studied. Ethanol at a concentration of 4 to 10% (v/v) reversibly inhibited the slice uptake of the organic anion, p-aminohippurate (PAH), in a dose-dependent manner, but had no significant effect on that of the organic cation, tetraethylammonium (TEA). Overall, the inhibitory effect on PAH uptake increased with the length of the hydrocarbon chain, with an I50 of 7.7, 0.9, and 0.05% for ethanol, butanol, and heptanol, respectively. The efflux of PAH was significantly decreased in the presence of 8% ethanol. Kinetic analysis indicated that ethanol decreased Vmax without a significant change in Km. Lowering the Na concentration in the incubation medium from 130 to 20 mM resulted in a disappearance of the above described inhibitory effect of ethanol on PAH uptake. Although Na-K-ATPase activity of renal cortical microsomes was significantly inhibited by ethanol (6-10%), butanol (1%), and heptanol (0.1%), there was no clear correlation between the effects of alcohols on PAH transport and/or Na-K-ATPase. Nevertheless, the results suggest that ethanol inhibits reversibly the Na-dependent transport of PAH from the medium into the cell across the basolateral membrane through a mechanism yet to be elucidated. The high degree of correlation between I50 and the partition coefficients of the alcohols suggested that their interaction with membrane lipids is important for the inhibition of PAH uptake, and also that PAH (but not TEA) transport is affected by alteration of the lipid environment of the membrane.
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PMID:Effect of ethanol on organic ion transport in rabbit kidney. 294 47


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