Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

The cellular mechanisms by which nephrotoxic heavy metals injure the proximal tubule are incompletely defined. We used extracellular electrodes to measure the early effects of heavy metals and other sulfhydryl reagents on net K+ and Ca2+ transport and respiration (QO2) of proximal tubule suspensions. Hg2+, Cu2+, and Au3+ (10(-4)M) each caused a rapid net K+ efflux and a delayed inhibition of QO2. The Hg2(+)-induced net K+ release represented passive K+ transport and was not inhibited by barium, tetraethylammonium, or furosemide. Both Hg2+ and Ag+ promoted a net Ca2+ uptake that was nearly coincident with the onset of the net K+ efflux. A delayed inhibition of ouabain-sensitive QO2 and nystatin-stimulated QO2, indicative of Na+, K(+)-ATPase inhibition, was observed after 30 sec of exposure to Hg2+. More prolonged treatment (2 min) of the tubules with Hg2+ resulted in a 40% reduction in the CCCP-uncoupled QO2, indicating delayed injury to the mitochondria. The net K+ efflux was mimicked by the sulfhydryl reagents pCMBS and N-ethylmale-imide (10(-4) M) and prevented by dithiothreitol (DTT) or reduced glutathione (GSH) (10(-4) M). In addition, both DTT and GSH immediately reversed the Ag(+)-induced net Ca2+ uptake. Thus, sulfhydryl-reactive heavy metals cause rapid, dramatic changes in the membrane ionic permeability of the proximal tubule before disrupting Na+, K(+)-ATPase activity or mitochondrial function. These alterations appear to be the result of an interaction of the metal ions with sulfhydryl groups of cell membrane proteins responsible for the modulation of cation permeability.
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PMID:Sulfhydryl-reactive heavy metals increase cell membrane K+ and Ca2+ transport in renal proximal tubule. 230 68

Respiration, membrane potential generation and motility of the marine alkalotolerant Vibrio alginolyticus were studied. Subbacterial vesicles competent in NADH oxidation and delta psi generation were obtained. The rate of NADH oxidation by the vesicles was stimulated by Na+ in a fashion specifically sensitive to submicromolar HQNO (2-heptyl-4-hydroxyquinoline N-oxide) concentrations. The same amounts of HQNO completely suppressed the delta psi generation. Delta psi was also inhibited by cyanide, gramicidin D and by CCCP + monensin. CCCP (carbonyl cyanide m-chlorophenylhydrazone) added without monensin exerted a much weaker effect on delta psi. Na+ was required to couple NADH oxidation with delta psi generation. These findings are in agreement with the data of Tokuda and Unemoto on Na+-motive NADH oxidase in V. alginolyticus. Motility of V. alginolyticus cells was shown to be (i) Na+-dependent, (ii) sensitive to CCCP + monensin combination, whereas CCCP and monensin, added separately, failed to paralyze the cells, (iii) sensitive to combined treatment by HQNO, cyanide or anaerobiosis and arsenate, whereas inhibition of respiration without arsenate resulted only in a partial suppression of motility. Artificially imposed delta pNa, i.e., addition of NaCl to the K+ -loaded cells paralyzed by HQNO + arsenate, was shown to initiate motility which persisted for several minutes. Monensin completely abolished the NaCl effect. Under the same conditions, respiration-supported motility was only slightly lowered by monensin. The artificially-imposed delta pH, i.e., acidification of the medium from pH 8.6 to 6.5 failed to activate motility. It is concluded that delta mu Na+ produced by (i) the respiratory chain and (ii) an arsenate-sensitive anaerobic mechanism (presumably by glycolysis + Na+ ATPase) can be consumed by an Na+ -motor responsible for motility of V. alginolyticus.
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PMID:The sodium cycle. I. Na+-dependent motility and modes of membrane energization in the marine alkalotolerant vibrio Alginolyticus. 242 48

The initial mechanisms of injury to the proximal tubule following exposure to nephrotoxic heavy metals are not well established. We studied the immediate effects of silver (Ag+) on K+ transport and respiration with extracellular K+ and O2 electrodes in suspensions of renal cortical tubules. Addition of silver nitrate (AgNO3) to tubules suspended in bicarbonate Ringer's solution caused a rapid, dose-dependent net K+ efflux (Km = 10(-4) M, Vmax = 379 nmol K+/min/mg protein) which was not inhibited by furosemide, barium chloride, quinine, tetraethylammonium, or tolbutamide. An increase in the ouabain-sensitive oxygen consumption rate (QO2) (13.9 +/- 1.1 to 25.7 +/- 4.4 nmol O2/min/mg, P less than 0.001), was observed 19 sec after the K+ efflux induced by AgNO3 (10(-4) M), suggesting a delayed increase in Na+ entry into the cell. Ouabain-insensitive QO2, nystatin-stimulated QO2, and CCCP-uncoupled QO2 were not significantly affected, indicating preserved function of the Na+,K+-ATPase and mitochondria. External addition of the thiol reagents dithiothreitol (1 mM) and reduced glutathione (1 mM) prevented and/or immediately reversed the effects on K+ transport and QO2. We conclude that Ag+ causes early changes in the permeability of the cell membrane to K+ and then to Na+ at concentrations that do not limit Na+,K+-ATPase activity or mitochondrial function. These alterations are likely the result of a reversible interaction of Ag+ with sulfhydryl groups of cell membrane proteins and may represent initial cytotoxic effects common to other sulfhydryl-reactive heavy metals on the proximal tubule.
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PMID:Silver ion (Ag+)-induced increases in cell membrane K+ and Na+ permeability in the renal proximal tubule: reversal by thiol reagents. 245 93

Hydrogen gas production was observed to occur during ATP-driven H+/K+ exchange in anaerobically grown E. coli. Neither process was found in aerobically grown cells or anaerobic cells grown on nitrate medium or when the osmotic pressure was decreased or K+ removed, or finally when DCCD, arsenate or CCCP was applied. Dithiothreitol restored the process even in the presence of CCCP but not in other cases of inhibition. A model of a multienzyme transport super-complex is proposed. The supercomplex consists of three genetically independent mechanisms: F0F1 H+-ATPase to provide energy, the K+-transporting Trk system as energy sink and formate-hydrogen lyase as donor of reducing equivalents. Within this supercomplex direct transduction of energy is accomplished via oxidation of 2 SH to S-S.
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PMID:Formation of an ion transport supercomplex in Escherichia coli. An experimental model of direct transduction of energy. 246 24

In microsomal vesicles, as isolated from exocrine pancreas cells, MgATP-driven H+ transport was evaluated by measuring H+-dependent accumulation of acridine orange (AO). Active H+ uptake showed an absolute requirement for ATP with simple Michaelis-Menten kinetics (Km for ATP 0.43 mmol/liter) with a Hill coefficient of 0.99. H+ transport was maximal at an external pH of 6.7, generating an intravesicular pH of 4.8. MgATP-dependent H+ accumulation was abolished by protonophores, such as nigericin (10(-6) mol/liter) or CCCP (10(-5) mol/liter), and by inhibitors of nonmitochondrial H+ ATPases, such as NEM or NBD-Cl, at a concentration of 10(-5) mol/liter. Inhibitors of both mitochondrial and nonmitochondrial H+ pumps, such as DCCD (10(-5) mol/liter) or Dio 9 (0.25 mg/ml), reduced microsomal H+ transport by about 90%. Vanadate (2 x 10(-3) mol/liter), a blocker of those ATPases, which form a phosphorylated intermediate, did not inhibit H+ transport. The stilbene derivative DIDS (10(-4) mol/liter), which inhibits anion transport systems, abolished H+ transport completely. MgATP-dependent H+ transport was found to be anion dependent in the sequence Cl- greater than Br- greater than gluconate-; in the presence of SO2-4, CH3COO- or No-3, no H+ transport was observed. MgATP-dependent H+ accumulation was also cation dependent in the sequence K+ greater than Li+ greater than Na+ = choline+. As shown by dissipation experiments in the presence of different ion gradients and ionophores, both a Cl- and a K+ conductance, as well as a small H+ conductance, were found in the microsomal membranes. When membranes containing the H+ pump were further purified by Percoll gradient centrifugation (ninefold enrichment compared to homogenate), no correlation with markers for endoplasmic reticulum, mitochondria, plasma membranes, zymogen granules or Golgi membranes was found. The present data indicate that the H+ pump located in microsomes from rat exocrine pancreas is a vacuolar- or "V" -type H+ ATPase and has most similarities to that described in endoplasmic reticulum, Golgi apparatus or endosomes.
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PMID:Characterization of MgATP-driven H+ uptake into a microsomal vesicle fraction from rat pancreatic acinar cells. 246 2

Pyranine was employed as a sensitive pH indicator in a low light level microspectrofluorometer. The in vivo and in vitro standard curves of the 460/410-nm fluorescence excitation ratio of pyranine as a function of pH are identical. Therefore, pyranine is specifically sensitive to cytoplasmic pH in Dictyostelium. The cytoplasmic pH of single cells in a population of Dictyostelium discoideum amoebae was obtained for the first time. The median cytoplasmic pH of vegetative amoebae was 7.19. Carbonyl cyanide m-chlorophenylhydrazone, a mitochondrial uncoupler and a protonophore, lowered the median cytoplasmic pH to 6.12 when the extracellular pH was 6.1. This result is in accord with the protonophore activity of carbonyl cyanide m-chlorophenylhydrazone. Interest in the cytoplasmic pH of Dictyostelium has been greatly stimulated by the theory that cytoplasmic acidification promotes development of pre-stalk cells, while cytoplasmic alkalinization favors the pre-spore pathway (Gross, J. D., J. Bradbury, R. R. Kay, M. J. Peacey. 1983. Nature (Lond.). 303:244-245). The theory postulates that diethylstilbestrol (DES), an inducer of stalk cell differentiation and a plasma membrane proton translocating ATPase inhibitor, should cause acidification of the cytosol. Previous measurements of the effects of stalk cell inducers including DES on intracellular pH using 31P nuclear magnetic resonance measurements have failed to confirm the predictions of the theory, and have suggested that significant modification of the model may be required. Using pyranine as the pH indicator, we find that the median cytoplasmic pH in cells treated with 10 microM DES dropped from 7.19 to pH 6.02. This effect is consistent with the pharmacological action of DES and with the proposal that DES, a stalk cell inducer, should acidify the cytosol. These results provide direct support for the theory that cytoplasmic pH is an essential regulator of the developmental pathway in Dictyostelium.
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PMID:Measurement of the cytoplasmic pH of Dictyostelium discoideum using a low light level microspectrofluorometer. 284 8

The ATP-H2O back-exchange reaction catalyzed by membrane-bound chloroplast coupling factor 1 (CF1) in the light is known to be extensive; each reacting ATP molecule nearly equilibrates its gamma-PO3 oxygens with H2O before it dissociates from the enzyme. Pi, ASi, ADP, and GDP, alternate substrates of photophosphorylation, each inhibit the exchange reaction. At all concentrations of these substrate/inhibitor molecules tested, the high extent of exchange per molecule of ATP that reacts remains the same, while the number of ATP molecules experiencing exchange decreases. Thus, these inhibitors appear to act in a competitive-type manner, decreasing ATP turnover, as opposed to modulating the rate constants responsible for the partitioning of E X ATP during the exchange reaction. This is consistent with the identity of CF1 catalytic sites for ATP-H2O back-exchange and ATP synthesis. Carbonyl cyanide m-chlorophenylhydrazone and NH4Cl (uncouplers of photophosphorylation) and phloridzin (an energy-transfer inhibitor) also lower the rate of ATP-H2O back-exchange; they too are found to act by decreasing the turnover of the ATP pool, not the extent of exchange per reacting ATP molecule. The extent of ATP-H2O forward oxygen exchange, which occurs during net ATP synthesis prior to product dissociation, is unaffected by uncouplers, whether catalyzed by native CF1 (ATPase latent) or the dithiothreitol/light-activated ATPase form. The mode of NH4Cl inhibition of the ATP synthesis reaction, therefore, is not through a change in the partitioning of the E X ATP complex.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mechanisms by which reactions catalyzed by chloroplast coupling factor 1 are inhibited: ATP synthesis and ATP-H2O oxygen exchange. 286 51

Escherichia coli batch cultures were grown under aerobic and anaerobic conditions on glucose with the substrate addition at pH 7.0. The cultures accumulated acetate in the medium at concentrations sufficient to inhibit the growth. This inhibitory effect of acetate was mediated apparently via its action on the intracellular pH. The inhibition of E. coli growth by acetate increased when the redox proton pump was switched off in the course of transition from aerobiosis to anaerobiosis and when the regulation of K+ fluxes was disordered in the presence of valinomycin. H+-ATPase was not essentially involved in maintaining the high rate of E. coli growth in the presence of acetate under aerobic conditions. If the activity of H+-ATPase was inhibited under anaerobic conditions at pH 7.0, the growth ceased after the dissipation of ionic gradients on the membrane. When CCCP was added under aerobic conditions, the growth did not stop at once if the medium had a pH of 7.6, but ceased immediately at pHout 7.0 in the glucose-salt medium.
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PMID:[Effect of the activity of primary proton pumps on the growth of Escherichia coli in the presence of acetate]. 290 16

Oligomycin-sensitive ATPase activity was studied in isolated yeast mitochondria. The protonophore CCCP, at a concentration which completely inhibited ATP synthesis, induced only a low rate of hydrolysis of externally added ATP, and the extent of hydrolysis was dependent upon phosphate (Pi) concentration. CCCP promoted hydrolysis of intramitochondrial ATP. However, hydrolysis of externally added ATP was total in a medium containing potassium phosphate plus valinomycin. Without ionophores, ATPase activity was only observed at high external pH or with detergent-treated mitochondria. Under state 4 conditions, external ATP had access to the catalytic nucleotide site of ATPase as shown by 32Pi-ATP exchange experiments. These results are discussed in terms of a limitation of the translocase-mediated ATP/ADP exchange in uncoupled mitochondria.
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PMID:Deficiency of uncoupler-stimulated adenosine triphosphatase activity in yeast mitochondria. 294 1

Subcellular vesicles of Vibrio alginolyticus hydrolyze ATP and accumulate Na+ in an ATP-dependent fashion. The Na+ uptake is (i) strongly stimulated by delta psi-discharging agents, i.e., the protonophorous uncoupler CCCP or valinomycin + K+ and (ii) arrested by DCCD at a concentration strongly inhibiting ATP hydrolysis. Lower concentrations of DCCD stimulate the Na+ accumulation supported by ATP hydrolysis as well as by NADH oxidation. It is concluded that there is an electrogenic DCCD-sensitive Na+-ATPase in the cytoplasmic membrane of V. alginolyticus.
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PMID:The ATP-driven primary Na+ pump in subcellular vesicles of Vibrio alginolyticus. 296 82


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