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

Previous studies showed that Ca2+ induced monomer to active dimer interconversion of a mitochondrial ATPase inhibitor protein from bovine heart or rat skeletal muscle (Yamada, E.W., Huzel, N.J. and Dickison, J.C. (1981) J. Biol. Chem. 256, 10203-10207). Initial equilibrium dialysis measurements of Ca2+ binding showed that this unique protein possesses three binding sites of high affinity with a maximum of one mol of Ca2+ bound/mol of protein monomer. Magnesium (1 mM) did not affect the first association constant but increased the second and third by about 1.2 and 1.5 fold, respectively. That the apparent association constants varied with concentration of protein monomer was in agreement with the self-associating nature of the protein. Scatchard plots at three concentrations of protein intersected at a molar ratio of about 0.5 (Ca2+/monomer). Ka1 and Ka2 values of 4.2 microM and 12.1 microM, respectively, were estimated by extra-polation of apparent constants to infinite dilution of protein. Ka3 (51.3 microM) was estimated by extrapolation of double reciprocal plots of apparent constants versus protein concentration to infinite levels of protein. A model for Ca2+ binding by this self-associating protein is described. Trifluoperazine had no effect on the activity of the inhibitor protein from either tissue.
Cell Calcium 1985 Dec
PMID:Ca2+-binding properties of a unique ATPase inhibitor protein isolated from mitochondria of bovine heart and rat skeletal muscle. 293 56

Effects of the calcium antagonists bepridil and nicardipine on mitochondrial functions were studied and their effects on respiratory control and calcium fluxes were compared. Results show that bepridil and nicardipine similarly increase Ca2+ intracellular movements, but that intramitochondrial Ca2+ storage is increased by bepridil whereas it is decreased by nicardipine. The in vivo significance of these findings remain to be determined. The effect of bepridil might be related to an enhancement of mitochondrial ATPase activity whereas nicardipine would act on mitochondria by a different mechanism.
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PMID:Comparative study of bepridil and nicardipine action on respiration and calcium transport in mitochondria. 295 41

The in vitro effects of piperine on three bioenergetic reactions namely, oxidative phosphorylation, ATPase activity and calcium transport by isolated rat liver mitochondria have been investigated. Piperine was found to inhibit state 3 and DNP-stimulated respiration by mitochondria respiring with glutamate plus malate or succinate as substrates. The I50 values of piperine on oxidative phosphorylation in the presence of glutamate plus malate and succinate were 22 and 12 micrograms/mg mitochondrial protein respectively. With HTM preparations, the oxidation of added NADH and succinate was depressed by piperine while ascorbate plus TMPD oxidation was slightly affected. Piperine did not inhibit the mitochondrial ATPase activity induced by DNP, but by itself exerted stimulating activity on this enzyme. Piperine was also found to diminish calcium uptake and to facilitate the release of accumulated calcium by the mitochondria incubated with succinate or ATP. These results suggest that piperine inhibits mitochondrial oxidative phosphorylation at the level of respiratory chain, and the inhibitory site(s) is in the segment(s) ahead of cytochrome C. The mechanism of the piperine-induced ATPase activity is not known; but the effect of piperine on calcium transport is likely to be consequential to the effects of this compound on the mitochondrial respiratory chain and ATPase activity.
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PMID:Effects of piperine on bioenergetic functions of isolated rat liver mitochondria. 296 41

Polar membrane in Campylobacter jejuni has been visualized on membrane vesicles. It was composed of doughnut-shaped particles 5-6 nm in diameter, with stalks, arranged in a hexagonal array. This structure was stabilized on the membrane by a high ionic strength buffer in the presence of 2-mercaptoethanol. Histochemical staining indicated localized ATPase activity at the poles of the cells. An ATPase with distinctive properties has been isolated and purified from this organism; it gives a specific activity of approximately 0.3 units/mg of protein. Electron microscopy showed doughnut-shaped particles 5-6 nm in diameter. Nondissociating and sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the purified enzyme revealed, respectively, a single band with ATPase activity and a molecular weight of ca. 75,000 Da. The enzyme was cold labile and activity was abolished by trypsin. Dicyclohexylcarbodiimide inhibited the membrane-bound form of the enzyme, but did not inhibit the soluble form. Oligomycin had no inhibitory activity on either form of the enzyme. The enzyme specifically hydrolysed ATP, but other nucleotide substrates were not degraded. The enzyme was activated by Mg2+ and inhibited by Ca2+, whereas other ions had no effect on activity. Antibodies prepared to this enzyme bound to the polar regions of whole cells as shown by protein A - colloidal gold immunoelectron microscopy. The antibodies to this ATPase cross reacted (shown by Western blotting) with four proteins from a whole-cell extract of this organism, two proteins in Aquaspirillum serpens MW5, and three proteins from Escherichia coli K12. They did not cross-react with any proteins from Spirillum volutans, Methanococcus voltae, Vibrio cholerae, or rat liver mitochondria. Antibodies raised against the F1-ATPase of E. coli K12 cross reacted with six proteins in a whole-cell extract of this organism, and one protein species in each of the whole-cell extracts of V. cholera, A. serpens MW5, S. volutans, and rat liver mitochondria. These antibodies did not recognize any whole cell proteins from either C. jejuni or M. voltae. These results along with the ATPase activity localized by histochemical staining suggest that polar membrane is an assembly of ATPase molecules at the poles of the cell and that the ATPase isolated from C. jejuni is serologically and structurally unusual.
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PMID:The ultrastructure and ATPase nature of polar membrane in Campylobacter jejuni. 297 56

Psychosine, sphingosylphosphorylcholine (52-104 microM), and other glycosphingolipids stimulate mitochondrial respiration (up to 500%) and inhibit oxidative phosphorylation to varying degrees. Above 104 microM these functions as well as uptake of Ca2+ are prevented. At 104 microM sphingosylphosphorylcholine inhibits the mitochondrial ATPase reaction in submitochondrial particles by 48%. Both sphingosylphosphorylcholine and psychosine enhance the active phosphate-dependent swelling of mitochondria. Passive swelling occurs in the presence of rotenone (when swelling does not normally occur) and under hypotonic conditions. A direct interaction of sphingosylphosphorylcholine with membranes is demonstrated by a discharge of the proton gradient across mitochondrial membranes, hemolysis of red blood cells, and binding to inner and outer mitochondrial membranes. Thus lysosphingolipids bind strongly to mitochondrial membranes and markedly alter mitochondrial function. This alteration would affect the ATP levels, thereby altering a wide range of ATP-dependent cellular functions. These results offer a partial explanation for the pathogenesis of representative lysosomal storage diseases.
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PMID:Lysosphingolipids and mitochondrial function. II. Deleterious effects of sphingosylphosphorylcholine. 297 68

Novocaine segregation zones in frog's erythrocytes, isolated by differential centrifugation, were shown to be ATPase active. The enzyme displays half of its maximum activity at 0.18 Mm ATP concentration to be inhibited by high concentrations of ATP. ATPase is activated by both Mg2+ and Ca2+ (in a lesser degree), with the maximum activity being at pH 7.5. A 5 minutes heating without the substrate results in decreasing the enzyme activity at 30 degrees, and in the total inhibition at 50 degrees C. Along with ATP, the enzyme can hydrolyse GTP and, in a lesser degree, ADP and sodium pyrophosphate. The ATPase activity is not effected with oligomycin (0.5-1.5 mkg/ml) or ouabaine (0.1 mM). Oligomycin in concentration 5 micrograms/ml induced non-specific inhibition of ATPase. Uncouplers, like 2,4-dinitrophenol and carbonyl cyanid p-trifluorometoxyphenylhydrazone, stimulate the enzyme activity. The lack in the ATP-ase sensitivity to oligomycin (specific inhibitor of mitochondrial F1-ATPase) and ouabaine (specific inhibitor of Na+, K+-ATPase) may suggest that the ATPase activity of novocaine segregation zones in frog's erythrocytes is not associated with a random contamination with mitochondria or cytoplasmic membranes. The ATPase under study has much in common with the lysosomal +H-ATPase. The results obtained support a hypothesis that +H-ATPase may function as a course of protones for maintaining acidic medium in segregation zones and promote accumulation of weak bases by means of their protonation.
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PMID:[ATPase activity of the novocaine segregation zones isolated from the erythrocytes of the common frog]. 298 28

Intramitochondrial Sr2+, similar to Ca2+, inhibits oxidative phosphorylation in intact rat-liver mitochondria. Both Ca2+ and Sr2+ also inhibit the hydrolytic activity of the ATPase in submitochondrial particles. Half-maximal inhibition of ATPase activity was attained at a concentration of 2.5 mM Ca2+ or 5.0 mM Sr2+ when the concentration of Mg2+ in the medium was 1.0 mM. The inhibition of ATPase activity by both cations was strongly decreased by increasing the Mg2+ concentration in the reaction medium. In addition, kinetical data and the determination of the concentration of MgATP, the substrate of the ATPase, in the presence of different concentrations of Ca2+ or Sr2+ strongly indicate that these cations inhibit ATP hydrolysis by competing with Mg2+ for the formation of MgATP. On the basis of a good agreement between these results with submitochondrial particles and the results of titrations of oxidative phosphorylation with carboxyatractyloside or oligomycin in mitochondria loaded with Sr2+ it can be concluded that intramitochondrial Ca2+ or Sr2+ inhibits oxidative phosphorylation in intact mitochondria by decreasing the availability of adenine nucleotides to both the ADP/ATP carrier and the ATP synthase.
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PMID:Inhibition of oxidative phosphorylation by Ca2+ or Sr2+: a competition with Mg2+ for the formation of adenine nucleotide complexes. 302 7

Control of mitochondrial respiration depends on ADP availability to the F1-ATPase. An electrochemical gradient of ADP and ATP across the mitochondrial inner membrane is maintained by the adenine nucleotide translocase which provides ADP to the matrix for ATP synthesis and ATP for energy-dependent processes in the cytosol. Mitochondrial respiration is responsive to the cytosolic phosphorylation potential, ATP/ADP.Pi which is in apparent equilibrium with the first two sites in the electron transport chain. Conventional measures of free adenine nucleotides is a confounding issue in determining cytosolic and mitochondrial phosphorylation potentials. The advent of phosphorus-31 nuclear magnetic resonance (P-31 NMR) allows the determination of intracellular free concentrations of ATP, creatine-P and Pi in perfused muscle in situ. In the glucose-perfused heart, there is an absence of correlation between the cytosolic phosphorylation potential as determined by P-31 NMR and cardiac oxygen consumption over a range of work loads. These data suggest that contractile work leads to increased generation of mitochondrial NADH so that ATP production keeps pace with myosin ATPase activity. The mechanism of increased ATP synthesis is referred to as 'stimulus-response-metabolism' coupling. In muscle, increased contractility is a result of interventions which increase cytosolic free Ca2+ concentrations. The Ca2+ signal thus generated increases glycogen breakdown and myosin ATPase in the cytosol. This signal is concomitantly transmitted to the mitochondria which respond to small increases in matrix Ca2+ by activation of Ca2+-sensitive dehydrogenases. The Ca2+-activated dehydrogenase activities are key rate-controlling enzymes in tricarboxylic acid cycle flux, and their activation by Ca2+ leads to increased pyridine nucleotide reduction and oxidative phosphorylation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Control of mitochondrial respiration in muscle. 305 Apr 50

The production (synthesis or release or both) of endothelium derived relaxant factor was studied in rabbit aortic strip preparations and an aortic-coronary artery bioassay system. Production of endothelium derived relaxant factor was rapidly inhibited by agents that inhibit mitochondrial electron transport or F1-ATPase, or which uncouple oxidative phosphorylation, but was only slowly impaired by inhibition of glycolysis. It was dependent also on the presence of extracellular calcium with a rapid on-off response time. This study shows that production of endothelium derived relaxant factor appears to be dependent on both oxidative phosphorylation and extracellular calcium.
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PMID:Production of endothelium derived relaxant factor is dependent on oxidative phosphorylation and extracellular calcium. 308 49

The effects of 2,5,2',5'-tetrachlorobiphenyl (25TCB) on parameters related to the bioenergetic functions of isolated rat liver mitochondria were investigated. State 3 respiration was inhibited by 25TCB with both succinate and glutamate/malate as the respiratory substrates. The extent of inhibition with succinate was larger than that observed with glutamate/malate. The concentration of 25TCB required to cause 50% inhibition for succinate was 51 microM, but with glutamate/malate, only 53% inhibition was observed at 200 microM. 25TCB stimulated state 4 respiration after 1-2 min lag period; state 4 respiration in the presence of glutamate/malate was more intensely stimulated by 25TCB than in the presence of succinate. 25TCB dissipated the membrane potential across the mitochondrial membranes. Isolated rat liver mitochondria accumulate large amounts of Ca2+ at the expense of respiration-linked energy (substrate oxidation) or of that provided by the hydrolysis of ATP by the mitochondrial ATPase. The Ca2+ accumulation by mitochondria was severely depressed by 25TCB when the energy was supplied by respiration. Furthermore, the inhibition of Ca2+ accumulation by 25TCB with succinate was greater than that produced with glutamate/malate. On the other hand, with ATP as the source of energy, 25TCB inhibited Ca2+ accumulation at high concentrations. 25TCB also released Ca2+ from mitochondria that had already accumulated Ca2+, indicating that mitochondrial membrane integrity was damaged by the intercalation of 25TCB. These results show that 25TCB impairs mitochondrial energy production, and inhibits Ca2+ sequestration by mitochondria.
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PMID:2,5,2',5'-Tetrachlorobiphenyl impairs the bioenergetic functions of isolated rat liver mitochondria. 309 39


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