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

---

Query: EC:3.6.1.3 (ATPase)
65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The acidity and lipophilicity of the fluorinated arylalkylsulphonamides are determined by the nature of the substituents on their aromatic rings. Herbicidal and anti-inflammatory effects of these compounds appear to increase with their lipophilicity. According to Mitchell's chemiosmotic theory, lipophilic weak-acid uncoupling agents act by transporting protons across the inner mitochondrial membrane and thus destroying the proton-electrochemical potential gradient required for ATP synthesis and ion transport. 1:1:1-Trifluoro-N-[2-methyl-4-(phenylsulphonyl) phenyl]methanesulphonamide (Perfluidone), a pre- and post-emergence herbicide (at 20 microM concentration), in isolated rat-liver mitochondria caused (1) a 2-fold stimulation of metabolic state-4 respiration, (2) a reduction of respiratory control ratio (RCR) by at least 50%, (3) an enhancement of latent ATPase activity by 40%, (4) a significant passive swelling of mitochondria in 0.15 N NH4Cl(delta A520 = -0.46 +/- 0.003), (5) proton intrusion during state-4 respiration (356 ng H+/min/mg protein; ng H+/min/mg protein with 5 microM perfluidone), and (6) at least 100% stimulation of oligomycin-inhibited respiration. These profiles are qualitatively comparable with those of the classical lipophilic weak-acid uncoupler, carbonylcyanide-trifluoro-methoxyphenylene hydrazone (FCCP), which acts by promoting the electrogenic transport of H+ ions across mitochondrial membrane.
...
PMID:Protonophoric properties of fluorinated arylalkylsulfonamides. Observations with perfluidone. 299 24

Oxygen electrode polarographic measurements of the rate of oxygen consumption by isolated rat liver mitochondria revealed that oligomycin inhibition of respiration was offset to different degrees by varying concentrations of perfluidone (1,1,1-trifluoro-N-(2 methyl-4-(phenylsulfonyl) methanesulfonamide). Using any of pyruvate-malate, succinate or ascorbate-TMPD (N,N,N',N'-tetramethyl-p-phenylenediamine) as substrate, this herbicidal and anti-inflammatory agent at 100 microM concentration caused a 5-fold stimulation of oligomycin-inhibited respiration. Higher concentrations of the herbicide (greater than or equal to 120 microM) gave lower stimulatory effects. Similar stimulatory effects were obtained with 1 microM FCCP (carbonylcyanide p-trifluoromethyoxyphenyl-hydrazone), a classical protonophore. Our results also show an enhanced oligomycin-sensitive ATPase action in intact mitochondria incubated with ATP and varying concentrations of perfluidone. Maximum enhancement effect (111.3%) was obtained at 120 microM perfluidone. FCCP (1 microM) stimulated this ATPase action by 130%. An initial inhibition of respiration by oligomycin is due to an interaction with the proton well of FOF1-ATP synthetase (Lardy, H.A. et al., Arch. Biochem. Biophys., 78 (1953) 587). Perfluidone probably increases the proton conductance of mitochondrial inner membrane in the same manner as FCCP and thus causes an increase in mitochondrial respiratory rate. As protons move into the matrix, delta mu H+, the proton electrochemical potential gradient becomes very small and the F0F1-ATP synthetase functions in the direction of hydrolysis of ATP rather than its shnthesis (Mitchell, P., Eur. J. Biochem., 95 (1979) 1). These findings therefore indicate that perfluidone acts in a way similar to FCCP, a classical uncoupler and protonophore.
...
PMID:Sensitivity of oligomycin-inhibited respiration of isolated rat liver mitochondria to perfluidone, a fluorinated arylalkylsulfonamide. 316 Jan 38

When cells of Streptococcus lactis or Escherichia coli were suspended in a potassium-free medium, a membrane potential (negative inside) could be artificially generated by the addition of the potassium ionophore, valinomycin. In response to this inward directed protonmotive force, ATP synthesis catalyzed by the membrane-bound ATPase (EC 3.6.1.3) was observed. The formation of ATP was not found in S. lactis that had been treated with the ATPase inhibitor, N,N'-dicyclohexylcarbodiimide, nor was it observed in a mutant of E. coli lacking the ATPase. Inhibition of ATP synthesis in S. lactis was also observed when the membrane potential was reduced by the presence of external potassium, or when cells were first incubated with the proton conductor, carbonylcyanidefluoromethoxyphenylhydrazone. These results are in agreement with predictions made by the chemiosmotic hypothesis of Mitchell.
...
PMID:A protonmotive force drives ATP synthesis in bacteria. 427 6

The release of Ca2+ from the terminal cisternae of sarcoplasmic reticulum in muscle fiber triggers muscle contraction. The signal for Ca2+ release is mediated via the triad junction, i.e. the junctional association of terminal cisternae and transverse tubule. Recently, highly purified morphologically intact triads were isolated from rabbit skeletal muscle (Mitchell, R. D., Palade, P., and Fleischer, S. (1983) J. Cell Biol. 96, 1008-1016). In this study, biochemical characterization of two variants of purified triad preparations (Pyrophosphate and Standard) is provided. Terminal cisternae of triads sequester Ca2+ at rates comparable to those of purified heavy sarcoplasmic reticulum which is referable to terminal cisternae (Meissner, G. (1975) Biochim. Biophys. Acta 389, 51-68). The permeability for calcium ions, as reflected by a 2-3-fold stimulation of (Ca2+, Mg2+)-ATPase activity in the presence of the Ca2+ ionophore A23187, and by the Ca2+ leak rate, is comparable in triads and heavy sarcoplasmic reticulum. Several transverse tubule characteristics are present in triads. Four of them, i.e. cholesterol content, ouabain binding, dihydroalprenolol binding (beta-adrenergic receptor), and ouabain-sensitive (Na+, K+)-ATPase activity, are comparably enriched in the Pyrophosphate triads and therefore appear to be quantitative indices of the amount of transverse tubule. Adenylate cyclase and basal ATPase are unreliable in this regard. Methodology for analyzing membrane integrity and sidedness was applied (adenylate cyclase activity) and modified (ouabain-sensitive (Na+, K+)-ATPase activity) to characterize the transverse tubule of the triad. In addition, a new method was developed making use of ouabain binding to study sidedness. These studies show that the transverse tubule is largely sealed and inside out in orientation, i.e. with the cytoplasmic face exposed. This report indicates that the t-tubule and sarcoplasmic reticulum components of the triads possess transport capability and retain permeability barriers for ions. Therefore, the isolated triads appear to be suitable for studying the physiological Ca2+ release process in vitro.
...
PMID:Biochemical characterization, integrity, and sidedness of purified skeletal muscle triads. 613 6

Ammonium chloride, an uncoupler of photophosphorylation which stimulates the membrane-bound chloroplast coupling factor ATPase when added after light/dithiothreitol activation, causes a decrease in the number of extra water oxygens incorporated into the phosphate formed during ATP hydrolysis. This observation is in contrast to the long-reported insensitivity of intermediate Pi:H2O oxygen exchange to uncoupler dinitrophenol in the mitochondrial F1 ATPase system. The effect of ammonium chloride on the CF1-catalyzed oxygen exchange reaction is consistent with ATPase activity stimulation caused by increased partitioning forward of the enzyme . products complex. In line with the oxygen exchange data, ammonium chloride causes an increase in the apparent Km of the enzyme for substrate ATP. The effect of ammonium chloride on the pattern of the intermediate Pi:H2O oxygen exchange is not a threshold phenomenon; the extent of exchange decreases in a continuous fashion, paralleling the stimulation of ATPase activity. The uncoupler CF3OPhzC(CN)2 also decreases the extent of oxygen exchange upon stimulating the membrane-bound ATPase, while phlorizin, an energy-transfer inhibitor, has essentially no effect on exchange although it inhibits the ATPase reaction. Similar to the effect of chemical uncoupling on the membrane-bound enzyme, physical removal of the coupling factor ATPase from the thylakoid membrane also results in an increase in forward partitioning of the enzyme . ADP . Pi complex. The modulation of oxygen exchange observed by altering the degree of coupling is similar to that which accompanies changing ATP concentration in the mitochondrial ATPase system [Russo, J. A., Lamos, C. M. and Mitchell, R. A. (1978) Biochemistry 17,473-480 and Choate, G. L., Hutton, R. L. and Boyer, P. D. (1979) J. Biol. Chem. 254, 286-290]. However, the uncoupler modulation is not readily correlated with the degree to which multiple catalytic sites are occupied by substrate.
...
PMID:Kinetic effects of chemical and physical uncoupling on the energy-transducing ATPase from spinach chloroplasts. 622 86

The F0F1-ATPase of the inner mitochondrial membrane catalyzes the conversion of a proton electrochemical energy into the chemical bond energy of ATP (Boyer, P.D., Chance, B., Ernster, L., Mitchell, P., Racker, E., and Slater, E.C. (1977) Annu. Rev. Biochem. 46, 955-1026). To assess the role of the membrane potential (delta psi) in this process and to study the effect of very short pulses on ATP synthesis, we employed a high voltage pulsation method (Kinosita, K., and Tsong, T.Y. (1977) Proc. Natl. Acad. Sci. U.S.A. 74, 1923-1927) to induce a delta psi of controlled magnitude and duration in a suspension of submitochondrial particles and F0F1-ATPase vesicles. Cyanide-treated submitochondrial particles were exposed to electric pulses of 10-30 kV/cm of magnitude (generating a peak delta psi of 150-450 mV) and 1-100 microseconds duration. Net [32P]ATP synthesis from [32P]Pi and ADP was observed with maximal values of 410 pmol/mg X pulse for a 30 kV/cm-100-microseconds pulse. This corresponds to a yield of 10-12 mol of ATP per mol of F0F1 complex per pulse. As many as 4 nmol/mg were produced after pulsing the same sample 8 times. By varying the ionic strength of the suspending medium, and consequently the pulse width, it is clearly shown that the synthesis was electrically driven and did not correlate with Joule heating of the sample. Titrations using specific inhibitors and ionophores were performed. The voltage-induced ATP synthesis was 50% inhibited by 0.11 microgram/mg of oligomycin and 2.4 nmol/mg of N,N'-dicyclohexylcarbodiimide. Ionophores and uncouplers had varying degrees of inhibition. The dependence of ATP synthesis on pulse width was nonlinear, exhibiting a threshold at 10 microseconds and a biphasic behavior above this value. Isolated F0F1-ATPase reconstituted into asolectin vesicles also synthesized ATP when pulsed with electric fields. A 35 kV/cm pulse induced the synthesis of 115 pmol of ATP per mg of protein, which corresponds to approximately 0.34 mol of ATP per mol of F0F1-ATPase. This synthesis was also sensitive to oligomycin and dicyclohexylcarbodiimide. The possibility of turnover of the ATPase in microseconds is considered.
...
PMID:Voltage-driven ATP synthesis by beef heart mitochondrial F0F1-ATPase. 623 68

A combined electron microscopic and graded tryptic dissection analysis of the catalytic protein of pure Na,K-motive ATPase reveals that the aspartyl phosphate residue-carrying catalytic center is located at the utmost radius of the hydrophilic cytoplasmic domain. This makes the cation-phosphate symport mechanism of Na/K transport across plasma membrane as proposed by Mitchell topologically unrealistic, and indirectly favors the mechanism of conformational coupling between the catalytic and ionophoric function of the transport system.
...
PMID:Utmost cytoplasmic location of catalytic center in Na,K-motive ATPase disfavors Mitchell's phosphate-cation symport mechanism of Na/K transport across plasma membrane. 631 46

The discovery in 1861 by Louis Pasteur that more yeast is formed aerobically than anaerobically per gram of glucose was the first clue to the difference in efficiency of glycolysis and oxidative phosphorylation. During the first half of the 20th century the pathway of glycolysis was untraveled. Individual enzymes and cofactors were isolated and characterized. A reconstituted system of all enzymes and cofactors catalyzed steady-state glycolysis, provided an appropriate ATPase was added. The need for an ATPase, clearly demonstrated in 1945 by Otto Meyerhof, remains an important aspect of glycolysis that has been sorely neglected by textbooks. The coupling of oxidation and phosphorylation and the formation of the high-energy intermediate 1,3-diphosphoglycerate, discovered by Otto Warburg, are the key reactions of glycolysis. A high-energy intermediate formed during this process was identified as a thiolester. Early concepts of the mechanism of oxidative phosphorylation based on this model led to some frustrating and confusing years of search for high-energy intermediates. Important contributions from the laboratories of Boyer, Cohn, Chance, Green, Lardy, and Lehninger elucidated the properties of the mitochondrial process. Then Peter Mitchell proposed in 1961, 100 years after the publication by Pasteur, that the "high-energy intermediate" is an electrochemical proton gradient generated by the electron transport chain and utilized by a proton turbine (the mitochondrial ATPase complex) to generate ATP. This concept is now widely accepted. Several problems remain to be solved. How are the protons translocated during electron transport? How many protons per site? What is the mechanism of ATP generation during proton flux via the mitochondrial ATPase?
...
PMID:From Pasteur to Mitchell: a hundred years of bioenergetics. 644 90

In order to determine the target portion of acetaminophen-induced hepatotoxicity, 750 mg per kg of body weight of acetaminophen was administered to male Wistar strain rats with or without the pretreatment of thiol compounds. In the liver, glutathione content decreased throughout the observation periods, and glutathione S-transferase initially, and later adenosine triphosphatase decreased, followed as elevations of aminotransferases and ornithione carbamoyltransferase in serum. The pretreatment of thiol compounds could not restore hepatic enzyme activities, but partially hepatic glutathione content and serum enzyme elevations. Although distinct time lag existed in biochemical alterations in the liver, hepatic glutathione content was significantly correlated solely with hepatic glutathione S-transferase. The mechanism of acetaminophen hepatotoxicity was discussed from the aspect of biochemical events in cytosol and membrane structure in hepatocytes. The mechanism of acetaminophen induced hepatotoxicity has been extensively investigated, and the hepatotoxicity seems to be related to the toxic metabolites generated by biotransformation process (Gillette et al., 1974, Mitchell et al., 1976). Since the toxic metabolites are conjugated with glutathione (GSH), it is generally accepted that when the hepatocellular GSH content has critically depleted, the metabolites seem to react with hepatocyte macromolecules and/or to produce lipid peroxidation, resulting in biochemical and structural changes leading to cell death (Black, 1980). A hepatotoxic dose of labelled acetaminophen was found throughout the liver and the highest concentration was found in centrilobular area, where considerable disruption and vacuolation of the plasma membrane and of the endoplasmic reticulum also occurred (Jollow et al., 1973, Chiu and Bhakthan, 1978). However remarkably little impairment of several enzyme systems in microsome, such as cytochrome P450 content, arylhydrocarbon hydroxylase and glucuronyl transferase has been reported (Thorgeirsson et al., 1976, Chiu and Bhakthan, 1978: Willson and Hart, 1977, Yamada et al., 1981). To elucidate the exact mechanism of acetaminophen hepatotoxicity, we observed time related biochemical alterations of hepatic GSH content, some marker enzymes in hepatocyte subfractions and serum enzymes. The present results indicated that acetaminophen reduced hepatic GSH content, followed as depletions of glutathione S-transferases (GSTs) and finally adenosine triphosphatase (ATPase), associated with elevations of serum enzymes.
...
PMID:The target portion of acetaminophen induced hepatotoxicity in rats: modification by thiol compounds. 666 1

Different inhibitors of the energy metabolism have been assayed in Escherichia coli K12 for their ability to increase the level of guanosine 5'-diphosphate 3'-diphosphate (ppGpp) as a consequence of a restriction of its degradation. Inhibitors of the respiration and uncouplers of oxidative phosphorylations had effects similar to carbon-source-induced downshifts while the ATPase inhibitor dicyclohexylcarbodiimide was less efficient. The effects of dicyclohexylcarbodiimide and of the uncoupler carbonylcyanide p-fluoro methoxyphenylhydrazone (FCCP) on ppGpp degradation were compared in a drug-permeable envelope mutant. At concentrations of inhibitors sufficient to deplete the pool of ATP by 50%, only FCCP was able to block ppGpp degradation. Moreover, FCCP also inhibited ppGpp degradation in a ATPase-deficient strain growing on glucose as carbon source while, as expected, it did not change the level of ATP. It is concluded, according to Mitchell's chemiosmotic hypothesis, that, in vivo, the integrity of the transmembrane proton gradient rather than the ATP pool size is a prerequisite for the normal processing of the energy-dependent degradation of ppGpp.
...
PMID:The energy-dependent degradation of guanosine 5'-diphosphate 3'-diphosphate in Escherichia coli. Lack of correlation with ATP levels in vivo and role of the transmembrane proton gradient. 698 54


<< Previous 1 2 3 4 Next >>

---