Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20020 (adenosine triphosphatase)
 3,299 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous experiments (Fukushima, Y., and Post, R.L. (1978) J. Biol. Chem. 253, 6853-6862) demonstrated that the Ca x phosphoenzyme of sodium- and potassium-transport adenosine triphosphatase gradually becomes stable after dissociation of Ca2+ in the presence of a chelating agent such as 1,2-cyclohexylenedinitrilo-tetraacetic acid. In the present study, we investigated whether the ADP- and K+-sensitive forms of the Ca x phosphoenzyme show different affinities for divalent cations. Our findings were as follows. (a) As the concentraion of Na+ was increased during phosphorylation of the enzyme with ATP at pH 7.4 and 0 degrees C, both the sensitivity to ADP and the amount of calcium-free phosphoenzyme increased in parallel. (b) For this Na+-dependent change, kidney enzyme required higher concentrations of Na+ than did brain enzyme. (c) In addition, the rate of dissociation of Ca2+ from the ADP-sensitive Ca x phosphoenzyme was faster than that from the K+-sensitive phosphoenzyme. It was thus concluded that Ca2+ binds to the ADP-sensitive phosphoenzyme less tightly than to the K+-sensitive phosphoenzyme.
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PMID:Changes in affinity of Na+- and K+-transport ATPase for divalent cations during its reaction sequence. 624 14

Monensin concentrations between 0.5 and 30 microM produced dose-dependent positive inotropy when administered to normal, electrically driven rabbit left atria. These doses did not produce contracture. When monensin was combined with very low concentrations of ouabain (10 or 50 nM), irreversible contracture, irregular responses to electrical stimulation, or both, occurred in a significant number of atria treated with both drugs. This was apparently due to intracellular Na+ overload produced by both drugs, with secondary elevations of intracellular Ca++ concentrations. Monensin (17 nM, 1.7 or 170 microM) did not inhibit canine myocardial Na+mK+-adenosine triphosphatase activity. When administered to mitochondria isolated from normal rabbit hearts, monensin concentrations greater than 10 nM significantly depressed ADP-stimulated (State 3) respiratory rates and calculated respiratory control ratios. Maximum inhibition of the respiratory control ratio (85% decrease) occurred with monensin concentrations of 1 microM or more. These concentrations also significantly decreased calculated ADP:0 ratios. The data show that monensin concentrations required to increase contractility of isolated myocardium can produce marked inhibitory effects on isolated mitochondria, but apparently do not do so when the drug is administered to intact, normal cardiac tissue.
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PMID:Subcellular actions and potential adverse cardiac effects of the cardiotonic ionophore monensin. 624 11

The rate of phosphorylation of sodium and potassium ion-transport adenosine triphosphatase by 10 microM [gamma-32P]ATP was much slower with Ca2+ than with Mg2+ (0.13-10 mM) in the presence of 16 to 960 mM Na+ at 0 degrees C and pH 7.4. In the presence of a fixed concentration of Mg2+ or Ca2+, the rate became slower with increasing Na+ concentration. When the Na+ concentration was fixed, the rate became slower with decreasing divalent cation concentration. Sodium ions appear to antagonize the divalent cation in the phosphorylation to slow its rate. In the presence of 1 mM Ca2+ and 126 or 270 mM Na+, the rate was slow enough to permit the manual addition of a chasing solution at various times before the phosphorylation reached the steady state. Therefore, we studied the time-dependent change of the sensitivity to ADP or to K+ of the phosphoenzyme by a chase with unlabeled ATP containing ADP or K+ during the time range from the transient to the steady state of the phosphorylation. The ADP sensitivity decreased and the K+ sensitivity increased with the progress of the phosphorylation. With 270 mM Na+, the phosphoenzyme found at 1 s, when its amount was 5.5% of the maximum level, was virtually completely sensitive to ADP. Under these conditions, it was concluded that the form of the phosphoenzyme initially produced from the enzyme.ATP complex has ADP sensitivity and that the phosphoenzyme acquires K+ sensitivity later. The initially produced ADP-sensitive phosphoenzyme partially lost its normal instability and sensitivity upon adding a chelating agent, probably because of dissociation of a divalent cation from the phosphoenzyme.
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PMID:Transient state in the phosphorylation of sodium- and potassium- transport adenosine triphosphatase by adenosine triphosphate. 626 64

Cellular oxygen consumption was monitored during stimulation and inhibition of the Na+- and K+-dependent adenosine triphosphatase in a suspension of intact tubules isolated from the rabbit renal cortex. Respiratory rates were compared to the ADP-stimulated respiratory rate (state 3 rate) obtained in mitochondria released directly from the renal tubules by digitonin shock. At 37 degrees C, in the presence of NADH-linked substrates and fats, isolated renal cells respire at 50 to 60% of the state 3 rate. Inhibition of the (Na+,K+)-ATPase with the cardiac glycoside, ouabain, results in a decline in respiration to 25 to 30% of the state 3 rate. Stimulation of the (Na+,K+)-ATPase produced as a result of nystatin-mediated dissipation of plasma membrane Na+ and K+ gradients results in increased respiration with an oxygen consumption rate characteristic of optimal ATP synthesis (state 3). The relationship between metabolic substrate regimen, mitochondrial respiratory capacity, and cellular energy demand is examined in the context of these findings.
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PMID:Mitochondrial respiratory capacity and Na+- and K+-dependent adenosine triphosphatase-mediated ion transport in the intact renal cell. 627 Jan 7

Adenosine triphosphatase activity of U. urealyticum is an integral membrane-bound protein which cannot be detached from the membrane by mild treatment with EDTA in low-ionic strength media nor by ionic detergents which rapidly inactivated the enzyme. The enzyme was Mg++ dependent; Mn++ and Co++ could replace Mg++ to some extent. A slight stimulatory effect was also exerted by sodium and lithium. The enzyme showed a nucleotide triphosphatase activity, but ADP was hydrolyzed at close to 40% the rate of ATP and other nucleotide monophosphatase were hydrolyzed at a very slow rate. Oubain and oligomycin did not inhibit the adenosine triphosphatase activity, whereas DCCD, NBD-Cl and several sulfhydryl-blocking reagents strongly reduced its activity. The enzyme could not be stimulated by trypsin pretreatment. It seems that the complex enzyme is tightly linked to the lipid bilayer of the membrane and differs in many aspects from the F0-F1 (Mg++, Ca++)-ATPase of bacteria.
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PMID:Adenosine triphosphatase activity of Ureaplasma urealyticum. 628 75

The gene product of the pleiotropic lon (also called capR) locus in Escherichia coli, the CapR protein, is an ATP hydrolysis-dependent protease and a nonspecific nucleic acid-binding protein. We demonstrated that it is also a DNA-stimulated adenosine triphosphatase (ATPase). This new activity is distinct from the protease-associated ATPase activity and occurs in the absence of proteolytic substrate. The reaction requires the presence of a divalent cation and has a pH optimum of 8.0. The products of the reaction are ADP and inorganic phosphate. No adenylation or phosphorylation of the DNA or proteins was detected. The maximum rate of ATP hydrolysis occurs in the presence of supercoiled (form I) DNA. Relaxed circles (form II), double-stranded DNA, and single-stranded DNA are less effective in promoting ATPase activity, whereas RNA is inactive. The DNA-stimulated ATPase activity is inhibited by a mutationally altered form of the CapR protein called the CapR9 protein. The interaction of the CapR and CapR9 subunits suggests that this enzymatic activity of the CapR protein is oligomeric in the presence of DNA. Our in vitro experiments indicate a possible role for nucleic acids in the regulation of all lon (capR) activity.
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PMID:DNA-stimulated ATPase activity on the lon (CapR) protein. 632 86

The catalytic and allosteric sites of proton translocating adenosine triphosphatase (ATPase) were studied by measuring the binding of nucleotides to the ATPase, and its alpha and beta subunits purified from thermophilic bacterium PS3, with a circular dichroic spectrometer. In contrast to mesophilic ATPases, this thermophilic enzmye contained no tightly bound nucleotides, and its subunits were stable after their purification. These properties were advantageous for analyzing both catalytic and allosteric sites. The former site showed rapid and loose binding, but the latter slow (t 1/2 = 1 h, for ADP) and tight binding. When a nucleotide was bound, the beta subunits showed a negative ellipticity at 275 nm corresponding to a tyrosyl residue, while the alpha subunits showed an ellipticity change corresponding to the absorption curve of the bound nucleotide. This difference enabled us to distinguish the binding sites in ATPase. At a low concentration, ADP selectively bound to alpha subunits in the ATPase, while at a high concentration, it bound to both subunits. This finding suggests that the tight binding sites are located in the alpha subunits. Although ADP and ATP bound to both the purified alpha and beta subunits, CTP did not bind to beta but only to alpha subunits, and ITP bound to beta but hardly to alpha. These nucleotide specificities also supported the idea that the catalytic sites are located in the beta subunits and the allosteric sites are located in the alpha subunits.
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PMID:Nucleotide binding to isolated alpha and beta subunits of proton translocating adenosine triphosphatase studied with circular dichroism. 644 45

We have found that when the ATP hydrolysis activity of beef heart mitochondrial adenosine triphosphatase (F1) is eliminated by either cold treatment or chemical modification, the enzyme attains the ability to catalyze the Pi in equilibrium ATP exchange reaction. The ATP hydrolysis activity of isolated F1 was lost upon chemical modification by phenyglyoxal, butanedione, or 7-chloro-4-nitrobenzene-2-oxa-1,3-diazole. The F1 thus chemically modified was able to catalyze an ADP-dependent Pi in equilibrium ATP exchange reaction. In addition F1 that had been cold-treated to eliminate ATP hydrolysis activity, also catalyzed the Pi in equilibrium ATP exchange reaction. The Pi in equilibrium ATP exchange catalyzed by modified F1 was shown to be totally inhibited by the F1-specific antibiotic efrapeptin. We have previously shown that isolated beef heart mitochondrial ATPase will catalyze the formation of a transition state analog of the ATP synthesis reaction (Bossard, M. J., Vik, T. A., and Schuster, S. M. (1980) J. Biol. Chem. 255, 5342-5346). While the F1-catalyzed ATP hydrolysis activity was lost rapidly upon chemical modification or cold treatment, the ability of the enzyme to produce Pi . adenosine 5'-diphosphate (chromium(III) salt) from phosphate and monodentate adenosine 5'-diphosphate (chromium(III) salt) was unimpaired. The implications of these data with regard to the mechanism of ATP synthesis are discussed.
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PMID:Catalysis of partial reactions of ATP synthesis by beef heart mitochondrial adenosine triphosphatase. 645 Jul 58

The ribose-modified nucleotides 2',3'-O-(2,4,6-trinitrophenyl) adenosine 5'-triphosphate (TNP-ATP) and TNP-ADP were used to probe the catalytic sites on soluble beef heart mitochondrial adenosine triphosphatase (F1). Both compounds were potent competitive inhibitors of ATP hydrolysis catalyzed by F1, Ki = 5.5 and 10 nM, respectively, and by submitochondrial particles, Ki (TNP-ATP) = 21 nM. Both compounds also were potent competitive inhibitors of ATP synthesis during oxidative phosphorylation (Ki = 1300 nM). Both analogs inhibited the 32Pi-ATP exchange reaction and the ATP-dependent reduction of NAD+ by succinate, catalyzed by submitochondrial particles. TNP-ATP and TNP-ADP were bound by F1. The presence of two binding sites on the enzyme for TNP-adenine nucleotides was determined by titrations of difference absorbance spectra, of the increase in fluorescence of the analog which occurred upon interaction with protein, and by titrations with the centrifuge column method using 32P-labeled TNP-adenine nucleotides. The first binding site bound the analogs with an affinity too high to be measured. The Kd for analog binding by the second site was 20 to 80 nM. In the presence of Mg2+, the 2 sites were filled with the TNP-ATP at a rate too rapid to be resolved by the procedure used. TNP-[gamma-32P]ATP was hydrolyzed by F1, Km = 0.2 microM, Vmax = 1.1 mol of 32Pi formed/mol of F1/s. It was shown, using the isotope trap technique as well as the inhibitor efrapeptin, that the 2 binding sites for TNP-ATP on F1 are hydrolytic sites.
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PMID:The presence of two hydrolytic sites on beef heart mitochondrial adenosine triphosphatase. 645 54

1. Binding of a P2x receptor specific radioligand, [3H]-alpha,beta-methylene adenosine triphosphate ([3H]-alpha,beta-MeATP) to sections of rat brain was reversible and association/dissociation parameters indicated that it consisted of two saturable components. Non-specific binding was very low (< 7% at 10 nM ligand concentration). 2. The binding was completely inhibited by suramin (IC50 approximately 14-26 microM) but none of the ligands specific for P2y receptors such as 2-methylthio-adenosine triphosphate (2-methyl-S-ATP) and 2-chloro-adenosine triphosphate (2-C1-ATP) nor 2-methylthio-adenosine diphosphate (2-methyl-S-ADP) a ligand for the P2 receptor on blood platelets ('P2T' type) produced strong inhibitions except for P1,P4-di(adenosine-5')tetraphosphate (Ap4A). 3. Inhibitors of Na+,K(+)-dependent adenosine triphosphatase (ATPase) ouabain, P1-ligand adenosine and an inhibitor of transport of, respectively, adenosine and cyclic nucleotides, dilazep, had no effect. 4. The highest density of P2x binding sites was found to be in the cerebellar cortex but the binding sites were present in all major brain regions, especially in areas known to receive strong excitatory innervation.
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PMID:Autoradiography of P2x ATP receptors in the rat brain. 767 Jul 31


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