Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.3.14 (ATP synthase)
 7,042 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Control of mitochondrial ATP synthase capacity was investigated in cultured cardiomyocytes from normotensive (Wistar-Kyoto) and spontaneously hypertensive (SHR) rats. The basal ATP synthase capacity in quiescent cardiomyocytes was raised in the hypertensive rats (2.9 +/- 0.1 mumol.min-1.mg protein-1) compared with normotensive rats (2.2 +/- 0.1 mumol.min-1.mg-1). However, this high value is restored to normal after treatment of the cells with verapamil or ruthenium red; agents that do not affect ATP synthase capacity in normal cells. It is concluded that abnormally high intramitochondrial Ca2+ levels, or an abnormal mitochondrial response to Ca2+ concentration, are responsible for ATP synthase activation in quiescent SHR cells. Cardiomyocytes from normotensive rats respond to increased energy demand (caused by electrical stimulation or treatment with positive inotropic agents) by increasing their ATP synthase capacity up to twofold. Cells from SHR rats are unable to control their ATP synthase in this way. It is concluded that some defect in regulation of the mitochondrial ATP synthase occurs in myocytes from hypertensive rats.
 ...
PMID:Defects in regulation of mitochondrial ATP synthase in cardiomyocytes from spontaneously hypertensive rats. 214 75

A previous communication (Fagian, M. M., Pereira da Silva, L. and Vercesi, A. E. (1986) Biochim. Biophys. Acta 852, 262-268) indicated that intramitochondrial calcium inhibits oxidative phosphorylation by decreasing the availability of adenine nucleotides to both the ADP/ATP translocase and the F0F1-ATP synthase complex. In this work we analyzed the interactions of calcium-nucleotide and magnesium-nucleotide complexes with the ATP synthase during catalysis of ATP in equilibrium with [32P]Pi exchange and net synthesis of ATP by submitochondrial particles. Concerning the ATP in equilibrium with [32P]Pi exchange reaction, calcium was ineffective as divalent cation when assayed alone. Furthermore, the addition of calcium increased the magnesium concentration required for half-maximal activation of the exchange, without changing Vmax. With respect to net ATP synthesis, the inhibition by calcium was shown to be due to formation of the CaADP- complex, which competes with MgADP- for the active site of the F0F1-ATP synthase. Moreover, ATP hydrolysis was competitively inhibited by CaATP2-, showing that calcium is able to interact with the enzyme in both forward and backward reactions in the same manner. That high calcium concentrations are required for significant inhibition of ATP synthesis indicates that this inhibition is relevant under conditions in which cytosolic calcium concentrations rise to pathological levels. Therefore, this mechanism may be responsible, in part, for the decrease in cellular ATP content that has been observed to occur when calcium accumulates in the cytosol.
 ...
PMID:Calcium inhibition of the ATP in equilibrium with [32P]Pi exchange and of net ATP synthesis catalyzed by bovine submitochondrial particles. 214 74

Several mutants of yeast lacking the porin gene have been found stable and viable on glucose or glycerol media. Ethanol-supported respiration of porin-free mutant and wild cells appeared equally coupled in vivo being similarly depressed by inhibitors of ADP/ATP translocase or of ATP synthase and stimulated by the uncoupler FCCP. The absence of porin in isolated mutant mitochondria hardly impaired the electron flux but increased the requirement for Mg2+ (or Ca2+) and for ADP and carboxyatractylate concentrations necessary to drive effectively state 3 - state 4 and state 4 - state 3 transitions, respectively. The existence of another porin species, possibly controlled by bivalent cations, is postulated.
 ...
PMID:The respiration of cells and mitochondria of porin deficient yeast mutants is coupled. 216 77

External electric fields of low intensity stimulated calcium influx in protoplasts isolated from carrot cell suspension cultures in field intensity dependent and frequency-dependent ways. The field-induced calcium uptake involved a temperature-dependent system that was saturable by external calcium. The induction process appeared mainly cumulative as long as the morphology of the protoplasts did not change (up to 10 min). The stimulation elicited by the electric fields was effective even after switching the field off; the influx increased for 5 min and then slowed down to its initial value 15 min later. During electrostimulation, an additional amount of ATP was accumulated; on removal of the stimulatory field, the extra amount of ATP was consumed, whereas the plasma membrane was hyperpolarized and sodium ions were expelled from the protoplasts. Inhibition of either ATP accumulation or consumption results in the inhibition of both calcium influx and sodium efflux, demonstrating that these processes are coupled. From the data obtained in this work, it may be concluded that the electric field stimulates an ATP synthase like activity; the consumption of the ATP thus formed elicits an electric potential (probably due to the efflux of cations and more specifically sodium) that drives the influx of calcium.
 ...
PMID:External electric fields stimulate the electrogenic calcium/sodium exchange in plant protoplasts. 217 97

It is generally believed that the initiation of insulin secretion by nutrient stimuli necessitates the generation of metabolic coupling factors, leading to membrane depolarization and the gating of voltage-sensitive Ca2+ channels. To establish this sequence of events, the kinetics of endogenous fluorescence of reduced pyridine nucleotides [NAD(P)H], reflecting nutrient metabolism, were compared to those of cytosolic calcium ([Ca2+]i) rises in single cultured rat islet beta-cells. In preliminary experiments, the loss of quinacrine fluorescence from prelabelled cells was used as an indicator of secretion. This dye is concentrated in the acidic insulin-containing secretory granules. Both glucose and 2-ketoisocaproate (KIC) raised [Ca2+]i in a dose-dependent manner. There was marked cellular heterogeneity in the [Ca2+]i response patterns. The two nutrient stimuli also increased NAD(P)H fluorescence, again showing cell-to-cell variations. In combined experiments, where the two parameters were measured in the same cell, the elevation of the NAD(P)H fluorescence preceded the rise in [Ca2+]i, confirming the statistical evaluation performed on separate cells. The application of two consecutive glucose challenges revealed coordinated changes in [Ca2+]i and NAD(P)H fluorescence. Finally, quinacrine secretion was stimulated by two nutrients with onset times similar to those recorded for [Ca2+]i elevations. These results clearly demonstrate that increased metabolism occurs during the lag period preceding Ca2+ influx via voltage-sensitive Ca2+ channels, a prerequisite for the triggering of insulin secretion by nutrient stimuli.
 ...
PMID:Single islet beta-cell stimulation by nutrients: relationship between pyridine nucleotides, cytosolic Ca2+ and secretion. 240 30

Ion-selective electrodes recorded the pH (7.49 +/- 0.05, n = 8) and pCa (6.72 +/- 0.03, n = 40) in samples (approximately 1 microliter) of isolated Myxicola axoplasm mounted within 760-micron diameter plastic tubes. We determined the interactions between Ca2+ and H+ on axoplasmic buffers by microinjecting CaCl2 or HCl into the axoplasmic samples at a distance 75-125 micron from the tips of the electrodes (distance = r). When axoplasmic pH was lowered 0.97 +/- 0.095 from its resting value (measured at r = 125 micron) by injecting 4 nmol HCl, pCa dropped 0.30 +/- 0.05 (n = 6). When expressed in units of concentration, these data show that a HCl injection of approximately 4 mmol/l axoplasm increased H+ and Ca2+ activity by approximately 0.3 microM. Lowering axoplasmic pCa 2.20 +/- 0.43 (r = 75 micron) (n = 3) by injecting 40 pmol CaCl2 had only a small effect on pH. In other experiments, two Ca2+ electrodes measured the Ca2+ activity 125 and 375 micron from the site of CaCl2 injection. Evidence of Ca2+ buffering was obtained when the Ca2+ activity at these two locations was below that expected for simple Ca2+ diffusion away from the injection site. Centrifuged axoplasm (100,000 g) taken from the bottom of the centrifuge tube had a somewhat greater Ca2+ buffering capacity than that taken from the top of the tube. Electron microscopic studies of the centrifuged axoplasm showed a greater concentration of mitochondria and other axoplasmic vesicles in the bottom of the centrifuge tube. Ruthenium red (20-40 micrograms/ml) greatly reduced Ca2+ buffering. The mitochondrial inhibitors CN (2 mM) and oligomycin (a mixture of oligomycin A, B, and C, 5 micrograms/ml) also reduced Ca2+ buffering but were not as effective as ruthenium red. Axoplasm in which ATP and mitochondrial substrates were removed by dialysis was unable to lower free Ca2+ when the concentration of this ion was elevated to approximately 10 microM. In the presence of oligomycin to block mitochondrial ATPase, and with Mg2+ -ATP as the only source of energy, axoplasm lowered Ca2+ activity slowly; with succinate as the only metabolic substrate, axoplasm rapidly lowered the Ca2+ activity from approximately 10 microM to below 1 microM.
 ...
PMID:Calcium and proton buffering and diffusion in isolated cytoplasm from Myxicola axons. 242 Jan 93

After the proposal of the chemiosmotic theory by Mitchell (1966, 1979) it has been recognized that different membrane-bound enzymes are able to use the energy derived from ionic gradients for the synthesis of ATP. These include the F1-ATPases of mitochondria and chloroplasts, the Ca2+-dependent ATPase of sarcoplasmic reticulum and the (Na+,K+)-ATPase of plasma membrane. In these systems the process of energy transduction is fully reversible. The enzyme can use the energy derived from the hydrolysis of ATP to build up a concentration gradient of ions across the membrane and, in the reverse process, use the energy derived from the gradient to synthesize ATP. Another interesting system in which these forms of energy are interconverted is found in photosynthetic bacteria. In chromatophores of Rhodospirillum rubrum there is a membrane-bound pyrophosphatase that, like the transport ATPases, catalyses the synthesis of pyrophosphate from Pi when a light-dependent proton gradient is formed across the chromatophore membrane. Like F1-ATPase, this enzyme is also able to generate an electrochemical potential gradient of protons at the expense of pyrophosphate hydrolysis. The mechanism by which the energy derived from a gradient is used by membrane-bound enzymes to catalyse the synthesis of high-energy phosphate compounds is still far from understood. Among the different enzymes studied, Ca2+-dependent ATPase is probably the system in which most is known about the mechanism of energy transduction. We now know of experimental conditions which allow us to move the different intermediary steps of the catalytic cycle of the enzyme in the direction of ATP synthesis. Thus, ATP synthesis can be attained after a single catalytic cycle in the absence of a transmembrane Ca2+ gradient. The net synthesis of ATP can be promoted by a variety of perturbations, including Ca2+, pH and water activity. These experiments indicate that during the catalytic cycle different forms of energy are interconverted by the Ca2+-dependent ATPase. The ultimate step of the cycle seems to be a change of water activity within the catalytic site of the ATPase. A common feature of all membrane-bound enzymes mentioned above is that during the catalytic cycle there are steps in which the hydrolysis of a phosphate compound (ATP, pyrophosphate or an acyl phosphate residue) is accompanied by only a small change in free energy. In conditions similar to those found in the cytosol, the hydrolysis of these phosphate compounds is accompanied by a much larger change in free energy.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Role of water in processes of energy transduction: Ca2+-transport ATPase and inorganic pyrophosphatase. 242 74

The mannose receptor mediates the transport of high-mannose glycoproteins from the cell surface to lysosomes in macrophages. The binding of ligand to the receptor is dependent on both pH and Ca2+. Upon internalization, ligands enter an acidic pre-lysosomal compartment where receptor-ligand dissociation takes place. Acidification is driven by an endosomal proton pump and anion transport is coupled to this acidification step. A permeabilized-cell assay has been designed to characterize the ionic requirements for receptor-ligand dissociation in endosomes. The plasma membrane of macrophages has been permeabilized selectively with digitonin without affecting endosomal membranes. Receptor-ligand dissociation in permeabilized cells required ATP and was blocked by proton ionophores. Di-isothiocyanostilbene-disulphonic acid and N-ethylmaleimide also blocked dissociation, but mitochondrial ATPase inhibitors and vanadate were ineffective. To explore the nature of the anion requirement for acidification, the ability of different anions to compensate for Cl- was tested. For the halide series, Br- was as equally effective as Cl- in supporting receptor-ligand dissociation, but I- was inhibitory. Citrate and gluconate were only partially effective, while SO4(2-), NO3- and PO4(2-) blocked dissociation. Addition of Ca2+ to permeabilized-cell preparations impaired ATP-dependent dissociation without affecting endosome acidification. These results suggest that the endosomal membrane has a Ca2+ conductance that would permit the rapid efflux of Ca2+ from endosomes during acidification, and this would appear to be a necessary step for efficient sorting of Ca2+-dependent receptors from their ligands.
 ...
PMID:The use of permeabilized cells to study the ion requirements of receptor-ligand dissociation in endosomes. 247 13

The effects of gramicidin S (GS), an antibiotic, on the rat heart membrane ATPases and contractile activity of the right ventricle strips were investigated. GS inhibited sarcolemmal Ca2+-stimulated ATPase (IC50 = 3 microM), Ca2+/Mg2+ ATPase which is activated by millimolar Ca2+ or Mg2+ (IC50 = 3.4 microM), and sarcoplasmic reticulum Ca2+-stimulated ATPase (IC50 = 6 microM). The type of inhibition for the sarcolemmal Ca2+/Mg2+ ATPase by GS was apparently uncompetitive, while that for Ca2+-stimulated ATPases in sarcolemma or sarcoplasmic reticulum was of mixed type. Other ATPases, including mitochondrial ATPase, sarcolemmal Na+-K+ ATPase, and myofibrillar ATPase, were not inhibited by this agent. GS also decreased the rat right ventricle maximum force development (half-maximal inhibitory concentration was 2-4 microM), maximum velocity of contraction, and maximum velocity of relaxation. The resting tension was increased by GS to over 200%. The contractile actions of GS were mostly irreversible upon washing the muscle 3 times over a 10-min period. Decreased Ca2+, Mg2+, Na+, K+ concentrations in the perfusate increased the effects of GS. These findings showed that GS was a potent inhibitor of divalent cation ATPases of heart sarcolemma and sarcoplasmic reticulum and it is suggested that these membrane effects may explain the cardiodepressant action of this agent.
 ...
PMID:Influence of gramicidin S on cardiac membrane Ca2+/Mg2+ ATPase activities and contractile force development. 247 7

Divalent cations are divided into two groups in relation to their ability to promote ATP synthase catalyzed reactions. In the presence of Mg2+, the following pattern rules: (i) uncoupler-stimulated ATP hydrolysis of Rhodospirillum rubrum chromatophores which shows an optimum concentration of the divalent cation; (ii) ATP-induced proton pumping in chromatophores; (iii) light-induced ATP synthesis in chromatophores; (iv) no or very low ATPase activity of purified F1-ATPase unmasked by diethylstilbestrol or n-octyl beta-D-glucopyranoside. In the presence of Ca2+, the following pattern occurs: (i) no stimulation of the ATP hydrolysis in chromatophores by carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone; (ii) no ATP-induced proton pumping; (iii) no light-induced ATP synthesis; (iv) a high ATPase activity of the purified F1-ATPase which is inhibited by diethylstilbestrol and n-octyl beta-D-glucopyranoside. Co2+, Mn2+, and Zn2+ are members of the "Mg2+-group", whereas Cd2+ is suggested to fall between the two groups. Intrinsic uncoupling of the membrane-bound ATP synthase has been suggested to account for the effect caused by Ca2+ in chloroplasts [Pick, U., & Weiss, M. (1988) Eur. J. Biochem. 173, 623-628]. Such an interpretation is consistent with our results on chromatophores. The uncoupling cannot occur at the level of the membrane since neither light-induced nor Mg-ATP-induced proton pumping is affected by Ca2+. A conformational change is suggested to be the reason for this intrinsic uncoupling, and it is proposed to be controlled by the diameters of the divalent cations (Ca2+ greater than Cd2+ greater than Mn2+ greater than Co2+ greater than Zn2+ greater than Mg2+).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Division of divalent cations into two groups in relation to their effect on the coupling of the F0F1-ATPase of Rhodospirillum rubrum to the protonmotive force. 248 79


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>