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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)

Aldehyde analogues of the normal alcohol substrates induce ATPase activities by glycerokinase (D-glyceraldehyde), fructose-6-phosphate kinase (2,5-anhydromannose 6-phosphate), fructokinase (2,5-anhydromannose or 2,5-anhydrotalose), hexokinase (D-gluco-hexodialdose), choline kinase (betaine aldehyde), and pyruvate kinase (glyoxylate). Since purified deuterated aldehydes give V and V/K isotope effects near 1.0 for glycerokinase, fructokinase with 2,5-anhydro[1-2H]talose, hexokinase, choline kinase, and pyruvate kinase, the hydrates of these almost fully hydrated aldehydes are the activators of the ATPase reactions. Fructose-6-phosphate kinase and fructokinase with 2,5-anhydro[1-2H]mannose show V/K deuterium isotope effects of 1.10 and 1.22, respectively, suggesting either that both hydrate and free aldehyde may be activators (predicted values are 1.37 if only the free aldehyde activates the ATPase) or, more likely, that the phosphorylated hydrate breaks down in a rate-limiting step on the enzyme while MgADP is still present and the back-reaction to yield free hydrate in solution is still possible. 18O was transferred from the aldehyde hydrate to phosphate during the ATPase reactions of glycerokinase, fructose-6-phosphate kinase, fructokinase, and hexokinase but not with choline kinase or pyruvate kinase. Thus, direct phosphorylation of the hydrates by the first four enzymes gives the phosphate adduct of the aldehyde, which decomposes nonenzymatically, while with choline kinase and pyruvate kinase the hydrates induce transfer to water (metal-bound hydroxide or water with pyruvate kinase on the basis of pH profiles). Observation of a lag in the release of phosphate from the glycerokinase ATPase reaction at 15 degrees C supports the existence of a phosphorylated hydrate intermediate with a rate constant for breakdown of 0.035-0.043 s-1 at this temperature. Kinases that phosphorylate creatine, 3-phosphoglycerate, and acetate did not exhibit ATPase activities in the presence of keto or aldehyde analogues (N-methylhydantoic acid, D-glyceraldehyde 3-phosphate, and acetaldehyde, respectively), possibly because of the absence of an acid-base catalytic group in the latter two cases. These analogues were competitive inhibitors vs. the normal substrates, and in the latter case, the hydrate of acetaldehyde was shown to be the inhibitory species on the basis of the deuterium isotope effect on the inhibition constant.
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PMID:Mechanisms of aldehyde-induced adenosinetriphosphatase activities of kinases. 609 91

Cation-dependent ATPase activities of rat liver plasmamembranes incubated "in vitro" with 4-hidroxy-2,3-nonenal (HNE, an aldehyde from peroxidative decomposition of biological membrane lipid moieties) are investigated. Mg++-ATPase activity is inhibited significantly by all the doses of HNE used (13,9, 4,1,1,2, 0,35 and 0,10 microM). Evidences for the inhibition of Mg++- Na+- K+- ATPase activity are also presented. Ca++- ATPase activity is strongly increased when rat liver plasmamembranes are incubated in presence of HNE 13,9 microM. Our results suggest that HNE may play a role in the control of intracellular cation levels acting directly on mechanisms of plasmamembranes ion transport.
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PMID:[Changes in the adenosinetriphosphatase activity in plasma membranes incubated in vitro in the presence of 4-hydroxy-2,3-nonenal]. 612 8

To elucidate possible causes of the hepatocyte swelling and necrosis found in alcoholic liver disease, the effects of ethanol and acetaldehyde on the activities of two hepatic plasma membrane ATPases--(Na+K+) ATPase and Mg2+ ATPase--were investigated. The activity of another plasma membrane-bound enzyme, 5' nucleotidase, was also determined to assess the specificity of these effects. Over concentrations ranging from 8 to 90 mM ethanol did not cause significant inhibition of any of the three enzymes. At 120 mM ethanol (Na+K+) ATPase activity was inhibited by 20% (P less than 0.01) and at higher concentrations there was progressive inhibition of all three enzymes that was non-competitive in type. Acetaldehyde produced non-competitive inhibition of (Na+K+) ATPase and Mg2+ ATPase at concentrations of 6 and 56 mM respectively and 5' nucleotidase activity was also inhibited at these concentrations. We conclude that ethanol and acetaldehyde inhibit (Na+K+) ATPase and Mg2+ ATPase activities as part of a generalised effect on the liver plasma membrane. Because the inhibitory concentrations of both substances are higher than are usually found in alcoholic subjects or in experimental animals after alcohol feeding, it seems unlikely that direct suppression of ATPase activity by ethanol or acetaldehyde is responsible for the morphological abnormalities of alcohol-induced liver disease. It could, however, be implicated in the development of hepatocellular necrosis in severe ethanol poisoning.
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PMID:Effects of ethanol and acetaldehyde on hepatic plasma membrane ATPases. 613 22

Chitose-6-P (2,5-anhydromannose-6-P) induces ATPase activity of fructose-6-P kinase with a Vmax 2-3% that of the normal kinase reaction with fructose-6-P or 2,5-anhydromannitol. Chitose (and presumably also chitose-6-P) is 52% hydrated in water while chitose deuterated at C-1 is 60% hydrated because of the equilibrium isotope effect of 0.73 on aldehyde hydration. Deuterated chitose-6-P gave a normal isotope effect on V/K of 1.23, but no effect on Vmax, showing that the free aldehyde is the activator and the hydrated form does not bind appreciably. With fructokinase, chitose can act either as a substrate, being phosphorylated at C-6 when adsorbed with C-6 next to MgATP, or as an inducer of ATPase activity when adsorbed with C-1 next to MgATP. The ATPase has a rate about 25% that of the kinase.
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PMID:Aldehyde-induced adenosine triphosphatase activities of fructose 6-phosphate and fructose kinases. 624 37

The interaction of synthetic ATP analogs, containing active groups in the triphosphate moiety and in the 8-position of the nucleotide molecule, with highly purified Na, K-ATPase from the medullar layer of porcine kidney was studied. It was found that 11 out of 17 ATP analogs studied irreversibly inhibit the ATPase activity of the enzyme. The pH optimum of the enzyme inactivation by adenosine-5'-(beta-chloroethylphosphate) and adenosine-5'-(p-fluorosulfonylphenylphosphate) beside the pronounced protective effect of ATP suggests possible covalent blocking of histidine and dicarboxylic amino acid residues in the enzyme active center. The irreversible inhibition of the enzyme by "oxo-ATP" containing aldehyde groups in the modified ribose residue in the presence of sodium borohydride suggests a possible presence of the lysine residue epsilon-amino group in the ATP binding site of the enzyme. Na, K-ATPase was found to possess an inorganic phosphate binding site, which is specifically blocked by chloromethylphosphonic acid. the accessibility of this site for modification depends on ATP, NA+ and K+.
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PMID:[Interaction of Na,K-ATPase with modifying ATP analogs and chloromethylphosphonic acid]. 626 76

In this report the disturbances in biochemistry of the heart muscle exposed to alcohol are delineated. All elements of cellular substructures are affected. In plasma membranes, (Na+ + K+)-activated ATPase (EC 3.6.1.3) is inhibited. Mitochondrial damage consists in diminished respiratory function and calcium uptake and binding. High-energy phosphates remain intact. Alcohol also affects the malate-aspartate shuttle. Acetaldehyde, a metabolite of ethanol, has a direct effect on myocardial protein synthesis through microsomal inhibition; however, the development of cardiac hypertrophy is not affected. Malfunction of sarcoplasmic reticulum is evidenced by disturbances in calcium binding and uptake. Effects of ethanol on the contractile machinery are deficiencies in the turnover rate of chemical into mechanical energy (diminished Vmax), and in the number of cross-bridges formed (P0). It increases stiffness of series elastic elements. There is diminished fatty acid oxidation with increased esterification. The involvement of CoA synthetase (EC 6.2.1.1), palmityl-carnitine transferase (EC 2.3.1.7), and pyruvate dehydrogenase complex in disturbed fatty acid oxidation is not certain. The role of catalase in myocardial ethanol oxidation was examined. Ethanol activates myocardial catalase-H2O2 complex (EC 1.11.1.6). The biochemical basis of fetal alcohol syndrome is low hepatic alcohol dehydrogenase (EC 1.1.1.1) activity during fetal life.
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PMID:Effect of alcohol on the heart and cardiac metabolism. 628 54

The effects of mild periodate exposure on the kinetics of (Na+ + K+)-ATPase and K+-p-nitrophenylphosphatase were studied using rat cerebral microsome preparations. Fifty percent inhibition of both enzyme activities was attained near 3 microM periodate concentrations. This inhibition was biphasic with time. Mg2+-ATPase and Mg2+-p-nitrophenylphosphatase activities were much less inhibited by periodate. Periodate inhibition was partially reversed by dimercaprol and dithiothreitol but not by diffusion. The possible reaction products formic acid, formaldehyde, glyceraldehyde, and acetaldehyde had no inhibitory effects in similar concentrations. Periodate exposure produced no detectable changes in the activation of (Na+ + K+)-ATPase by Na+, K+, Mg2+, or ATP. Residues shared by both (Na+ + K+)-ATPase and K+-p-nitrophenylphosphatase are both critical to hydrolytic function and sensitive to mild oxidation by periodate.
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PMID:Inhibition of rat brain microsomal (Na+ + K+)-ATPase and K+-p-nitrophenylphosphatase by periodic acid. 628 25

To determine whether and how ethanol and acetaldehyde alter brain oxidative metabolic activity, reduction/oxidation shifts of components of the mitochondrial respiratory chain were optically measured, in situ, from cat cerebral cortex. Oxidative shifts of nicotinamide adenine dinucleotide (NADH) were recorded in response to increased energy demand provoked by stimulation of the cortical surface by electrical pulses. Ethanol or acetaldehyde did not alter the direction of the responses but each slowed the rates of oxidation with little effect upon the rates of subsequent re-reduction. There was no apparent change produced by either drug upon the kinetics of the negative shifts of the cortical steady potential in response to the stimulation. However, stimulus-evoked electrical and metabolic responses were decreased in amplitude with increasing drug doses. It is suggested that the slowed mitochondrial oxidation results from inhibition of Na+, K+-ATPase. This supports the concept that ethanol or acetaldehyde inhibit the processes that lead to increased oxygen consumption following cell depolarization in vivo, as has been demonstrated in vitro.
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PMID:Ethanol and acetaldehyde alter brain mitochondrial redox responses to direct cortical stimulation in vivo. 629 68

Maternal ethanol consumption produces a reduction in postnatal growth. We have studied especially changes of liver and brain. This reduction is more marked if the alcoholic offspring are maintained with their biological mothers than if they are kept with surrogate mothers. Rats exposed prenatally to alcohol show a marked accumulation of fat in the liver and a significant proliferation of liver endoplasmic reticulum. No change in the postnatal development of liver alcohol (ADH) and acetaldehyde dehydrogenases (ALDH) (high and low Km) is observed in offspring from alcoholic mothers, with the exception of slightly higher ALDH (low Km) for the offspring that remain with alcoholic mothers. The postnatal development of the liver (Na+-K+) ATPase is also similar in control and alcoholic groups. However, in the case of the enzyme from the brain, a lower ATPase activity is observed in the group derived from alcoholic mothers. Interestingly, at 20 days of postnatal period, an induction of the ATPase (from liver and brain) was observed when the group of offspring from alcoholic mothers were kept on an alcohol diet.
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PMID:Effects of prenatal and postnatal exposure of rats to alcohol: changes in (Na+-K+) ATPase. 629 87

The incubation of isolated factor F1 with the di-aldehyde derivative of ADP (oxADP) which is formed as a result of ADP treatment by periodate, causes the covalent binding of 0.9--1 molecules of the oxADP with a molecule of the enzyme. This modification of factor F1 is not accompanied by any changes in the ATPase activity of the enzyme. The modification of factor F1 is preceded by the reversible binding of oxADP with the enzyme with a Kd of 80 micro M. ADP partly prevents factor F1 from modification by oxADP. The electrophoresis of modified factor F1 in polyacrylamide gel in the presence of sodium dodecyl sulphate showed that oxADP binds with the alpha-subunit(s) of factor F1. When submitochondrial particles are incubated with [3H]oxADP, the main part of the radioactive label may be discovered in the polypeptide with a molecular weight of some 30 000 which is probably the adenine nucleotides' translocase. The isolation of factor F1 from particles preincubated with [3H]oxADP showed that the membrane-bound factor F1 covalently binds 0.2--0.3 mol of oxADP per mol of enzyme. Here again, all the oxADP is bound with the alpha subunit(s) of factor F1. The modification of membrane-bound factor F1 by oxADP is accompanied by the partial inhibition of the particles' ATPase activity. The results obtained testify to the fact that the non-catalytic site of mitochondrial ATP ase located on the alpha-subunit(s) of factor F1 may participate in the mechanism of ATP hydrolysis by membrane-bound ATPase.
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PMID:The non-catalytic nucleotide-binding site of mitochondrial ATPase is localised on the alpha-subunit(s) of factor F1. 644 65


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