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)

The relative effectiveness of the ligands Mg2+, Na+, and ATP in preparing sodium plus potassium ion transport adenosine triphosphatase for phosphorylation was studied by means of a rapid mixing apparatus. Addition of 2 mM MgC12, 120 mM NaC1, and 5 muM [gamma-32P]ATP simultaneously to the free enzyme gave an initial phosphorylation rate of about 0.3 mu mol-mg-1-min-1 at 25 degrees and pH7.4. Addition of Mg2+ to the enzyme beforehand, separately or in combination with Na+ or ATP, had little effect on the initial rate. Addition of Na+ only to the enzyme beforehand increased this rate 1.5- to 3-fold. Early addition of ATP 130 ms before Na+ plus Mg2+ increased the rate 6- to 7-fold. Early addition of Na+ plus ATP was most effective; it increased the rate about 10-fold. The data indicate that Na+ and ATP bind in a random order and that each ligand potentiates the effect of the other. The rate of dissociation of ATP from the enzyme was estimated by a chase of unlabeled ATP of variable duration. This rate was slowest in the presence of Mg2+ (k = 540 min-1), most rapid in the presence of Na+ (k = 2000 min-1), and intermediate (k = 1100 min-1) in the absence of metal ions. The effect of Na+ concentration on the rate of phosphorylation was estimated when Na+ with Mg2+ was added to the enzyme-ATP complex. The rate followed Michaelis-Menten kinetics with a maximum of 2.9 mu mol-mg-1 and a Km of 8 mM. The effect of Na+ concentration was also estimated on the increment in the rate of phosphorylation produced by the presence of Na+ with the enzyme-ATP complex beforehand. The increment followed the same kinetics with a maximum of 3.75 mu mol-mg-1-min-1 and a Km of 5.4 mM. In both cases estimation of the Hill coefficient failed to show cooperativity between binding sites for Na+. In contrast, the dependence of ouabain-sensitive ATPase activity on Na+ concentration in the absence of K+ indicated two sites for Na+ with apparent Km values of 0.16 and 8.1 mM, respectively.
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PMID:Phosphorylation from adenosine triphosphate of sodium- and potassium-activated adenosine triphosphatase. Comparison of enzyme-ligand complexes as precursors to the phosphoenzyme. 13 2

The portion of Escherichia coli adenosine triphosphatase (ATPase) which is peripheral to the membrane (ECFl) is composed of five separate polypeptides referred to as alpha, beta, gamma, delta, and epsilon. Treating purified ECFl with pyridine precipitated the three larger polypeptides (alpha, beta, and gamma), but the two smaller ones (delta and epsilon), which represent only about 10% of ECFl, remained in solution. After removing the pyridine, both delta and epsilon were active and both were obtained in essentially pure form after chromatography on a single molecular-seive column. epsilon strongly inhibited the ATPase activity of ECFl, indicating that epsilon has a regulatory role in the enzyme. epsilon inhibited ECFl missing delta, indicating that delta is not required for inhibition by epsilon. However, enzyme containing just the alpha and beta subunits, which was prepared by treating ECFl with a protease, was fully active hydrolytically but not at all sensitive to inhibition by epsilon. This result suggests that the gamma polypeptide is required for the inhibition of the ATPase by epsilon. delta restored the capacity of ECFl missing delta to recombine with ECFl-depleted membrane vesicles. The ECFl, which became attached to the vesicles by the added delta, was functional in energy transduction, as evidenced by the coupling of ATP hydrolysis to the transhydrogenase reaction in the vesicles. The rebinding of ECFl missing delta was directly proportional to the amount of delta added until all the ECFl receptors in the membranes were occupied. delta may be a stalk which connects the Fl headpiece to the membrane, since the attachment of ECFl to the membrane exhibited an absolute dependence on delta. Although delta is known to have an apparent molecular weight of about 20,000 by gel electrophoresis in the presence of sodium dodecyl sulfate, the active delta eluted from a molecular-seive column with an apparent molecular weight of about 35,000, suggesting that in the active form delta is a dimer or rather elongated in shape. The active epsilon subunit eluted from the same column with an apparent molecular weight of about 16,000.
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PMID:Purification of membrane attachment and inhibitory subunits of the proton translocating adenosine triphosphatase from Escherichia coli. 13 33

We have demonstrated recently that grayanotoxin I (GTX I) produces a positive inotropic effect in isolated guinea-pig atria. In order to determine whether this effect of GTX I is related to the reported action of this compound to increase the sodium permeability of cytoplasmic membranes, the effect of GTX I and alpha-dihydrograyanotoxin II (alpha-2H-GTX II) on electrical and mechanical properties and transmembrane cation movements were studied in guinea-pig myocardium. In electrically driven guinea-pig left atrial preparations, both grayanotoxins produced a slight depolarization and appear to decrease the upstroke velocity of the action potential, with a concomitant increase in isometric contractile force in the presence or absence of propranolol. Pretreatment with propranolol shifted the dose-response curves for the inotropic effect of both grayanotoxins slightly to the right. The magnitudes of changes in the electrical and mechanical properties induced by GTX I and alpha-2H-GTX II were similar. The rate of development and subsequent washout of the positive inotropic effects, however, was faster with alpha-2H-GTX II than with GTX I, consistent with a previous report that the action of alpha-2H-GTX II to increase membrane sodium permeability develops more rapidly than that of GTX I. At higher concentrations, both grayanotoxins produced arrhythmias. Arrhythmias induced by GTX I were characterized by extrasystoles whereas those induced by alpha-2H-GTX II were characterized by initial extrasystoles followed by a failure of the atria to follow electrical stimulation. Positive inotropic and arrhythmic effects of both grayanotoxins were reversible after the washout of the drug. Both types of arrhythmias produced by either GTX I or alpha-2H-GTX II were reversed by tetrodotoxin, an agent which has been demonstrated to antagonize the action of the grayanotoxins to increase membrane sodium permeability. Although both grayanotoxins had no marked effect on partially purified Na+, K+-adenosine triphosphatase, they produced dose-dependent increases in ouabain-sensitive 86Rb uptake of ventricular slices under conditions in which the intracellular sodium concentration determines the rate of active monovalent cation transport by the Na+, K+-adenosine triphosphatase system. These data suggest that the positive inotropic effects of grayanotoxins are due to an increased membrane sodium permeability and are consistent with a hypothesis that alterations in transmembrane sodium movements result in an altered myocardial contractility.
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PMID:The effects of grayanotoxin I and alpha-dihydrograyanotoxin II on guinea-pig myocardium. 13 34

Antisera against each of the two major subunits of detergent-solubilized electroplax (sodium plus potassium)-activated adenosine triphosphatase from Electrophorus electricus were prepared. Antiserum against the small subunit (a glycoprotein, Mr = 58,000) partially inhibits [3H]ouabain binding to the enzyme, but does not interfere with the phosphorylation of enzyme. Conversely, antiserum against the large subunit (the catalytic subunit Mr = 96,000) partially inhibits phosphorylation of the enzyme, but does not interfere with the binding of [3H]ouabain to the enzyme. Since ouabain only interacts with enzyme from the outer surface of the membrane and phosphorylation of enzyme takes place on the inner surface of the membrane, the results suggest that the small subunits are exposed on the outer surface of the membrane, whereas the large subunits are oriented predominantely facing the cytoplasmic side.
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PMID:Molecular organization of subunits of electroplax (sodium plus potassium)--activated adenosine triphosphatase. 13 8

The effects of CdCl2 on adenosine triphosphatase (ATPase) were studied microsomal fractions or tissue homogenates of outer cortex, inner cortex and outer medulla of dog kidney. Cd was found to be an inhibitor of Na+ +K+ Atpase with 150 value of 2.1 to 3.2 X 10(-4) M regardless of type or source of the enzyme preparation tested. Mg++ ATPase was about 10-fold less sensitive to inhibition by Cd than Na+ +K+ ATPase. The inhibition of microsomal NA+ +K+ ATPase from outer medulla was characterized by irreversible kinetics. The inhibitory effect was not altered by varying Na+ or K+ concentrations, but was decreased by disodium ethylenediaminetetracetic acid (EDTA). EDTA was more effective in preventing than in reversing the inhibition. Na+ +K+ ATPase from kidneys of several other mammalian species showed a similar sensitivity to Cd.
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PMID:Inhibition of renal adenosine triphosphatase by cadmium. 13 65

Effect of digitalis on central sympathetic neurons have been proposed to alter sympathetic influences on the heart and to contribute to the induction of arrhythmias. Recently, however, we have presented evidence which indicates that the involvement of a direct central action of digitalis is negligible in the alteration of sympathetic nerve activity after i.v. administration of the drug. Thus, a group of experiments were designed to determine if central drug concentrations or biochemical events in the brain would suggest a central action of the drug. Tritiated digoxin (20 microng/kg) was injected i.v. into cats every 15 minutes until ventricular fibrillation occurred. The concentrations of digoxin in cerebrospinal fluid and serum increased linearly with time as the cumulative dose of digoxin was increased. At the mean arrhythmic dose, 140 microng/kg, cerebrospinal fluid contained approximately 10 nM digoxin whereas free digoxin concentration in serum was approximately 30 nM and total digoxin concentration in serum was approximately 120 nM. Since inhibition of Na+,K+-adenosine triphosphatase (Na+,K+-ATPase) is often associated with the pharmacological effects of digitalis, effects of nanomolar concentrations of digoxin on Na+,K+-ATPase activity were determined in vitro. The concentration of digoxin faund in cerebrospinal fluid at arrhythmia inhibited Na+,K+-ATPase only slightly (5-10%). Activity of Na+,K+-ATP-ase was also examined in brains of cats which had died in ventricular arrhythmias due to treatment with lethal dose of digitoxin. After ventricular fibrillation, the cat brains were removed and Na+,K+-ATPase activity and ouabain binding were determined in eight areas. No reduction in Na+,K+-ATPase activity or [3H]ouabain binding was observed in any area. Thus, it appeared that toxic doses of digitalis did not cause sail to provide evidence for central effects of toxic doses of digoxin or digitoxin.
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PMID:Digitalis toxicity: lack of marked effect on brain na+,k+-adenosine triphosphatase in the cat. 13 66

The activities of 5'-nucleotidase, K+, Na+-activated Mg2+-dependent adenosine triphosphatase (ATPase) and leucine-beta-naphthylamidase were determined from 17 rheumatoid synovial fluids and from extracts of the corresponding synovial tissues. There was little correlation between the enzyme activities in the synovial fluids and those in the respective synovial-tissue extracts. In seropositive cases of rheumatoid arthritis the activities of 5'-nucleotidase and leucine-beta-naphthylamidase in the synovial-tissue extract were higher than in seronegative cases. Also, the ratios of the enzyme activities in the synovial fluids to the resepctive activities in synovial tissue were lower in the seropositive cases. The activity of 5'-nucleotidase in the synovial tissue decreased during gold treatment.
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PMID:The activities of plasma-membrane marker enzymes in rheumatoid synovial tissues and fluids. 13 78

The synthesis of a 3beta-thioacetylcardenolide is described. The thioacetate exhibited effects similar to those seen with digitoxigenin acetate on the isolated frog and guinea pig hearts at 1 X 10(-7) dilution. In the intact rat heart, the lethal dose was 5 mg/kg for the thioacetate and 2.5 mg/kg for digitoxigenin acetate. The thioacetate inhibited sodium- and potassium-activated adenosine triphosphatase to the same extent as digitoxigenin, but it was somewhat less inhibitory than digitoxigenin acetate.
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PMID:Thiocardenolides II: synthesis and pharmacological evaluation of 3beta-thioacetyl-14beta-hydroxy-5beta-card-20(22)-enolide. 14 Feb 33

This study was undertaken to localize the enzyme sodium-potassium dependent adenosine triphosphatase in unstimulated human small lymphocytes using the histochemical technique of McClurkin [1964]. The substrate adenosine 5' triphosphate is hydrolyzed by the ATPase resulting in a lead phosphate precipitate at the site of enzyme action, subsequently visualized as lead sulphide. The enzyme was demonstrated in three different patterns, and for each donor the pattern was constant both on all four of the test slides, and on different occasions. The patterns observed were: clusters of granules related to the cell membrane; positive staining localized to portions of the cell membrane, and, less commonly, the whole cell circumference. The significance of this distribution may relate to areas with large numbers of antigen recognition sites on the lymphocyte membrane.
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PMID:Adenosine triphosphatase located on unstimulated human small lymphocyte cell membranes. 14 Apr 12

The possibility that augmentation of cardiac Na+-K+-dependent adenosine triphosphatase (Na-K-ATPase) by L-3,5,3'-triiodothyronine (T3) was mediated by early changes in intracellular ion concentrations ([Na+]1, [K+]1) was explored by time-course analysis after a single injection of T3 in thyroid-ablated (131I) rats. At 6 and 16 h after injection, T3 had no significant effect on cardiac [Na+]1, [K+]1, or microsomal Na-K-ATPase activity. At 24 and 48 h, however, T3 elicited proportionate increases in [K+]1 and Na-K-ATPase activity. Thus, no evidence was adduced that the T3-dependent increase in ventricular Na-K-ATPase activity is an adaptive response to prior changes in intracellular ion concentrations. The increase in [K+]1 is attributable to an increase in Na+ pump activity. Administration of T3 to hypothyroid rats had no effect on the transition temperature or the activation energy of ventricular microsomal Na-K-ATPase, as analyzed by an Arrhenius plot. Thus, the lipid microenvironment and the properties of the enzyme may be independent of thyroid status. The latter inference was supported by kinetic analysis, in that T3 had no effect on the Km for ATP or the K1/2's for Na+ and K+. Injection of T3 of the hypothyroid rat, however, significantly increased the Vmax's for ATP, Na+, and K+ of ventricular microsomal Na-K-ATPase. These results are in accord with the inference of thyroidal induction of Na-K-ATPase indistinguishable from those present in the athyroid state.
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PMID:Characteristics of thyroid-stimulated Na+-K+-ATPase of rat heart. 14 Jun 7


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