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)

A great deal of knowledge has been gained concerning the activation of adenylate and guanylate cyclase in epidermal cells. Adenylate cyclase is activated by 4 different independent receptors-responding respectively to catecholamine (beta), to prostaglandins (E), to histamine (H2), and to adenosine and it phosphorylated derivatives. Upon activation, each of these receptors becomes unresponsive to further stimulation by its specific stimulator. Guanylate cyclase, on the other hand, is activated by histamine (H1) and epidermal growth factor (EGF). Unlike EGF, the histamine activation is extremely rapid (less than 5 minutes). Epidermal cells are permeable (leak) to cyclic GMP but not cyclic AMP. When the skin is traumatized or injured in any way (even by intradermal injection) there is a sudden catastrophic change in the intracellular levels of the cyclic nucleotides (and of ATP). Cyclic AMP rapidly rises to perhaps 5-10 times its normal resting level while cyclic GMP falls to 10-20% of its level in vivo. The rise in cyclic AMP is due to activation of adenylate cyclase while the fall in cyclic GMP is due in major part to activation of cyclic GMP phosphodiesterase (and perhaps the fall in ATP is due to activation of ATPase). The changes in ATP and cyclic AMP can be reversed by incubating the tissue in a buffered salt solution containing glucose, but this does not normalize the cyclic GMP content. The fall in cyclic GMP can be prevented by a phosphodiesterase inhibitor (IBMX ). This series of events has been called the "ischemia effect." However, it implies that a lack of oxygen is at fault, and that has not been shown to be the case. Its underlying cause and possible physiologic significance are not known. Do these changes in cyclic nucleotides have effects on epidermal proliferation? And does EGF? Agents which increase cyclic AMP do inhibit the epidermal outgrowth and mitotic activity of explant cultures of pig skin. Cyclic GMP does increase outgrowth at a particular concentration. Histamine, which elevates both cyclic nucleotides, has a biphasic action depending on its concentration. These findings imply that these nucleotides do act as one of the controls of epidermal proliferation. The action of cyclic GMP is not accompanied by detectably increased phosphorylation of epidermal proteins. On the other hand, EGF action which also enhances epidermal outgrowth is characterized by an increased protein phosphorylation that precedes any increase in cellular cyclic GMP. We conclude that the action of EGF is independent of the cyclic nucleotide system.
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PMID:Cyclic GMP system in the epidermis. 626 50

The interaction between the (Na+ +K+)-ATPase and the adenylate cyclase enzyme systems was examined. Cyclic AMP, but not 5'-AMP, cyclic GMP or 5'-GMP, could inhibit the (Na+ +K+)-ATPase enzyme present in crude rat brain plasma membranes. On the other hand, the cyclic AMP inhibition could not be observed with purified preparations of (Na+ +K+)-ATPase enzyme. Rat brain synaptosomal membranes were prepared and treated with either NaCl or cyclic AMP plus NaCl as described by Corbin, J., Sugden, P., Lincoln, T. and Keely, S. ((1977) J. Biol. Chem. 252, 3854-3861). This resulted in the dissociation and removal of the catalytic subunit of a membrane-bound cyclic AMP-dependent protein kinase. The decrease in cyclic AMP-dependent protein kinase activity was accompanied by an increase in (Na+ +K+)-ATPase activity. Exposure of synaptosomal membranes containing the cyclic AMP-dependent protein kinase holoenzyme to a specific cyclic AMP-dependent protein kinase inhibitor resulted in an increase in (Na+ +K+)-ATPase enzyme activity. Synaptosomal membranes lacking the catalytic subunit of the cyclic-AMP-dependent protein kinase did not show this effect. Reconstitution of the solubilized membrane-bound cyclic AMP-dependent protein kinase, in the presence of a neuronal membrane substrate protein for the activated protein kinase, with a purified preparation of (Na+ +K+)-ATPase, resulted in a decrease in overall (Na+ +K+)-ATPase activity in the presence of cyclic AMP. Reconstitution of the protein kinase alone or the substrate protein alone, with the (Na+ +K+)-ATPase has no effect on (Na+ +K+)-ATPase activity in the absence or presence of cyclic AMP. Preliminary experiments indicate that, when the activated protein kinase and the substrate protein were reconstituted with the (Na+ +K+)-ATPase enzyme, there appeared to be a decrease in the Na+-dependent phosphorylation of the Na+-ATPase enzyme, while the K+-dependent dephosphorylation of the (Na+ +K+)-ATPase was unaffected.
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PMID:Regulation of rat brain (Na+ +K+)-ATPase activity by cyclic AMP. 628 69

48 patients with cerebral arteriosclerosis were found to have a manifest release of adenylate kinase (AK) into cerebrospinal fluid (CSF). This release was most probably due to an increased leak in the brain cells subsequent to a lowered adenylate charge potential followed by a diminished electrochemical potential in these cells suffering from disturbed oxygen supply. A further increase of AK release into CSF was noted for the 22 patients receiving cardiac glycosides compared to the 26 patients not treated with these drugs. The mean AK value of the former group was 0.119 +/- 0.028 U/l compared to that of the latter group, being 0.089 +/- 0.025 U/l, and this difference was significant (p less than 0.001). The effect of cardiac glycosides is most probably explained by an additional lowering of the membrane electrochemical potential in brain cells of these patients due to the direct action of cardiac glycosides on the Na+- and K+-dependent ATPase system in these cells, resulting in an increased leak in the plasma membrane.
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PMID:Effect of cardiac glycosides on the release of adenylate kinase into cerebrospinal fluid of patients with cerebral arteriosclerosis. 628 88

Influence of antiestrogen and antiandrogen derivatives of acylhydrazine, potentiating the antitumoral effect of cytostatics, on properties of nucleoside triphosphatases (NTPases), adenylate content in nuclea of normal and tumoral cells was studied. It was shown that acylhydrazines activated specifically the intranuclear NTPase of normal and tumoral cells. Activity of nuclear membrane-linked NTPases from liver cells was also increased after administration of acylhydrazines, sex hormones or phenobarbital. The increase in activity of intranuclear NTPase (namely ATPase) correlated with decrease of adenylates (ADP, ATP) in nuclea isolated from tumors after simultaneous treatment with acylhydrazines and thiophosphamide. Distinct increase in sensitivity of tumoral cell DNA to the effect of these alkylating preparations appear to be due to noncompensated decrease in content of ATP.
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PMID:[Effect of antiestrogen and antiandrogen derivatives of acylhydrazines on properties of nucleoside triphosphatases and adenyl nucleotide content of nuclei of normal and tumor cells]. 630 Nov 57

Gastric ulcer was elicited in rats by reserpine (5 mg x kg-1 sc.) administration. Ulcer formation (number and severity) was measured 6, 12, 18 and 24 hr after reserpine administration. At the time of killing of the animals, tissue levels of adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), cyclic adenosine monophosphate (cAMP) were measured enzymatically and by radioimmunoassay in the gastric fundal mucosa. The sum of ATP + ADP + AMP (adenylate pool) and the ratio of ATP x ADP-1 were calculated. It was found that (1) the tissue levels of ATP, AMP, cAMP, sum of ATP / ADP + AMP (adenylate pool) and ratio of ATP x ADP-1 increased significantly in the gastric fundal mucosa 6 hr after reserpine administration, thereafter these values decreased gradually and significantly; (2) the tissue level of ADP increased significantly in the gastric fundal mucosa 6 hr after reserpine administration, meanwhile its level increased significantly at 18 and 24 hr; (3) the value of energy charge (ATP + 0.5 ADP x ATP + ADP + AMP-1) remained unchanged; (4) the peaks of biochemical alterations in the gastric fundus mucosa preceded he appearance of ulcers. It was concluded that (1) reserpine ulcer appears after an active metabolic response in the rat gastric fundal mucosa; (2) hypoxaemic damage in the gastric fundal mucosa can be excluded as a possible underlying mechanism of ulcer formation produced by reserpine administration; (3) before the appearance of reserpine ulcer, significant changes in the feedback mechanism, system, i.e. between the ATP--membrane ATPase--ADP and the ATP--adenylate cyclase--cAMP energy systems, can be observed in the rat gastric fundal mucosa.
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PMID:Cellular energy systems and reserpine ulcer in rats. 632 19

Incubation of African green monkey kidney (BS-C-1) cells and mouse fibroblasts (3T6) in the presence of adenosine for 4 hours resulted in increases in the nuclear compartment pools of adenosine 5'-triphosphate (ATP) and nuclear ATP/adenosine 5'-diphosphate (ADP) ratios. Adenine and inosine, which yield increases in total cellular ATP pools and ATP/ADP ratios similar to those promoted by adenosine, do not produce similar increases in the nuclear compartment. Adenosine-promoted increases in nuclear ATP pools were higher in the untransformed, serially propagated, BS-C-1 cells than in the spontaneously transformed 3T6 cells. Adenosine-promoted compartmentalized ATP pools in primary chick embryo fibroblasts were reduced upon transformation of these cells with Rous sarcoma virus, resulting in free mixing of all of the ATP pools synthesized from various salvage precursors. The growth regulatory properties of the nuclear compartment pools of adenine nucleotides is suggested by the big increases in nuclear ATPase and adenosine 5'-monophosphate (AMP) deaminase activities upon the entry of 3T6 cells into the S phase of their cycle. These enzymatic activities would tend to lower the nuclear ATP/ADP ratios and reduce the total adenine nucleotide pools in these nuclei respectively--conditions which were shown by earlier in vitro studies to be favorable to DNA replication.
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PMID:Compartmentalized ATP pools produced from adenosine are nuclear pools. 645 Jul 72

Rat heart mitochondria oxidizing pyruvate (in the presence of 20% as much malate) took up nearly the amount of oxygen required for complete oxidation to CO2. Thus pyruvate, a physiological substrate of the citrate cycle, is oxidized through the entire cycle in these mitochondria, and they seem suitable for study of regulation of integrated mitochondrial energy transduction. By addition of graded amounts of hexokinase or pyruvate kinase to the suspending medium (in the presence of excess glucose or phosphoenolpyruvate), a wide range of steady-state values of the ATP/ADP concentration ratio was obtained. At a constant concentration of phosphate, the steady-state rate of oxygen uptake by rat heart mitochondria oxidizing pyruvate was a function of the adenylate energy charge or of the ATP/ADP ratio, and relatively independent of the absolute concentrations of these nucleotides. The oxygen uptake rates typically spanned a range of about 20-fold. At very high values of the ATP/ADP ratio, the rate of oxygen uptake is much lower than the "state 4" rate seen after added ADP has been phosphorylated. This result suggests that "state 4" respiration, at least in these freshly prepared mitochondria, measures the rate at which ADP is made available by ATPase activity, rather than indicating uncoupling of electron transport from phosphorylation. The concentration of orthophosphate affected the rate of oxygen uptake and the pattern of response to the ATP/ADP ratio or the energy charge, but the effects did not seem interpretable in terms of the mass-action expression for hydrolysis of ATP, (ATP)/ (ADP) (Pi).
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PMID:Adenine nucleotide control of the rate of oxygen uptake by rat heart mitochondria over a 15- to 20-fold range. 671 43

Treatment of a variety of human tumor cells in monolayer cultures with low levels (40 to 80 microM) of adenosine 5'-diphosphate (ADP) or adenosine 5'-triphosphate (ATP) was recently shown to produce arrest of cellular growth in the S phase of the cell cycle (E. Rapaport, J. Cell. Physiol., 114: 279-283, 1983). We now demonstrate that exposure of two well-characterized colonic adenocarcinoma (HT-29 and SW-620) and two pancreatic adenocarcinoma (CAPAN-1 and PANC-1) cell lines in soft-agar cultures to exogenously supplied 5 to 20 microM ATP results in substantial inhibition of cellular growth. Exposure of the cells to 5 to 20 microM ADP produces slightly smaller growth-inhibitory effects, while 20 microM adenosine 5'-monophosphate or adenosine have marginal effects on cellular proliferation in these systems. Successful demonstration of these effects requires the use of heat-inactivated fetal bovine serum, since normal fetal bovine serum possesses enzymatic activities which catalyze the rapid degradation of adenine nucleotides. Tumor cell growth was assayed by the well-established colony formation assay as well as by [3H]thymidine incorporation into acid-insoluble material. [3H]Thymidine incorporation is performed 4 to 14 days after plating and correlates well with results obtained by colony formation assays. Due to the ectoenzymatic activities of the cells which include adenosinetriphosphatase and adenosinediphosphatase catalyzing the dephosphorylation of ATP and ADP, the effective levels of ATP that inhibit the growth of human tumor cells in this system, which is widely claimed to predict the in vivo response of a tumor, are lower than the 5 to 20 microM which are exogenously supplied. The two previously characterized, well-differentiated pancreatic and colonic tumor cell lines (CAPAN-1 and HT-29) were shown to exhibit higher chemosensitivity towards treatment with ATP and ADP than did the lesser-differentiated pancreatic and colonic tumor cell lines (PANC-1 and SW-620).
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PMID:Growth inhibition of human tumor cells in soft-agar cultures by treatment with low levels of adenosine 5'-triphosphate. 687 73

The mathematical modelling of human erythrocyte energy metabolism has shown that stabilization of ATP concentration can be achieved if the curve representing the relation between glycolysis rate and ATP concentration (glycolysis characteristic) is bell-shaped with steeply descending part at physiologically normal ATP concentration. The glycolysis characteristic of human erythrocytes has been obtained experimentally. In erythrocytes of different donors the glycolysis characteristics are greatly different quantitatively, but have qualitatively similar bel-like shape with steeply descending part at physiologically normal ATP concentration. This characteristics can be made coincident for all donors if they are plotted in relative units taking for 100% the physiologically normal values of glycolysis rate and ATP for every individual donor. The coincidence of the normalized erythrocyte glycolysis characteristics for different donors can be achieved in the mathematical model of erythrocyte energy metabolism under the assumption that the phosphofructokinase rate depends effectively on the relation of ATP to adenylate pool and the total erythrocyte ATPase is strongly inhibited by AMP.
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PMID:Regulation of glycolysis in human erythrocytes. The mechanism of ATP concentration stabilization. 733 40

Arginyl-tRNA synthetase from Bacillus stearothermophilus (NCA 1518) has been purified 880-fold to apparent homogeneity as demonstrated by electrophoresis in the presence of sodium dodecyl sulphate. The molecular weight is 59 000 as confirmed by Sephadex G-100 and by sucrose gradient ultracentrifugation. The enzyme is monomeric, no subunits were detected. Its cognate tRNA induces an apparent increase in molecular weight suggesting the dimerisation of the enzyme. Nevertheless, it is not obvious that the enzyme dimer forms prior to the aminoacylation reaction catalysed by the enzyme. An ATPase activity was found associated to the synthetase but can be neglected because the ATP consumption is too low for hampering the arginyl-tRNA synthetase activity. The order of addition of substrates and release of products has been studied by measurements of initial velocity, product inhibition and dead-end inhibition. The nature of the kinetic patterns indicates that the aminoacylation reaction conforms to the classical concept of the mechanism which includes the formation of an enzyme-bound aminoacyl-adenylate as an intermediate in the first step followed by transfer of the amino acid to tRNA. The first partial reaction, measured by the ATP-32PPi exchange or AMP synthesis in the presence of ATP and arginine, requires tRNA, which is consistent with the model in which tRNAArg is an activator of the arginyladenylate synthesis.
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PMID:Arginyl-transfer ribonucleic acid synthetase of Bacillus stearothermophilus. Purification and kinetic analysis. 735 46


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