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:3.6.3.14 (ATP synthase)
7,042 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oxidation of ferrocytochrome c by molecular oxygen catalysed by cytochrome c oxidase (cytochrome aa3) is coupled to translocation of H+ ions across the mitochondrial membrane. The proton pump is an intrinsic property of the cytochrome c oxidase complex as revealed by studies with phospholipid vesicles inlayed with the purified enzyme. As the conformation of cytochrome aa3 is specifically sensitive to the electrochemical proton gradient across the mitochondrial membrane, it is likely that redox energy is primarily conserved as a conformational "strain" in the cytochrome aa3 complex, followed by relaxation linked to proton translocation. Similar principles of energy conservation and transduction may apply on other respiratory chain complexes and on mitochondrial ATP synthase.
...
PMID:The mechanism of energy conservation and transduction by mitochondrial cytochrome c oxidase. 20 Dec 86

Many intracellular organelles contain a unique primary, electrogenic proton pump termed the vacuolar H(+)-ATPase. This pump, found in many endocytic, secretory, and storage vesicles in fungal, plant and animal cells, functions, in conjunction with a chloride conductance, to acidify the vesicle interior. Although remotely related to the mitochondrial ATP synthase, the vacuolar H(+)-ATPase is a distinct pump which differs in inhibitor sensitivity, subunit composition and function. The vacuolar H(+)-ATPase transports only protons, and permeable anions (chloride) are required for optimal vesicle acidification. Allosteric and regulatory effects are not yet fully understood. Vesicle acidification appears to be essential for receptor-mediated endocytosis, protein synthesis, and secretion and storage of small solutes such as neurotransmitters. A similar plasma membrane-located H(+)-ATPase may contribute to urinary acidification and cell pH regulation.
...
PMID:Acid transport by intracellular vesicles. 216 27

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

At low concentrations, almitrine inhibits yeast cell multiplication by acting on oxidative metabolism. Studies on isolated mitochondria display the following features: (i) almitrine inhibits ATPase activity and decreases ATP/O ratio during oxidative phosphorylation; (ii) no direct effect on respiration can be evidenced; (iii) ATP/O value decreases without any change in the magnitude of delta p; (iv) the higher the ATP synthesis and respiratory fluxes, the larger is the decrease in ATP/O ratio induced by almitrine. These results indicate that almitrine does not act as a classical protonophoric uncoupler nor as previously studied non protonophoric uncouplers (e.g., general anesthetics). Our data show a direct inhibitory effect of almitrine on ATPase-ATP synthase complex. But, in contrast to the classical inhibitors of this complex, almitrine decreases the ATP/O ratio in a flux-dependent manner. Thus, almitrine could induce either an intrinsic uncoupling of H+/-ATPase (i.e., slip in this proton pump) or a change in the mechanistic H+/ATP stoichiometry at the ATPase level.
...
PMID:Almitrine, a new kind of energy-transduction inhibitor acting on mitochondrial ATP synthase. 252 61

The photoaffinity label 8-azido-ATP has been used to study the effect of inhibition of ATP synthase on ATP-driven reverse electron transfer from succinate to NAD+ ('reversal'), succinate- and NADH-driven ATP synthesis and ATP-Pi exchange. In reversal, where ATPase functions as primary proton pump, inactivation by covalently bound nitreno-ATP results in an inhibition that is proportional to the inactivation of ATP hydrolysis, or, consequently, with the concentration of inactivated ATP synthases. Up to 60% inactivation of the reversal rate does not lead to a decrease in delta mu H+. Inhibition of ATP synthase as secondary proton pump results in case of NADH-driven ATP synthesis in a proportional inhibition, but with succinate as substrate ATP synthesis is less than proportionally inhibited, compared with inactivation of ATP hydrolysis. Inhibition of one of the primary pumps of NADH-driven ATP synthesis, the NADH:Q oxidoreductase, with rotenone also resulted in an inhibition of the rate of ATP synthesis proportional to that of the NADH oxidation. ATP-Pi exchange is much more affected than ATP hydrolysis by photoinactivation with 8-azido-ATP. Contrary to reversal and NADH-driven ATP synthesis the rate of ATP-Pi exchange does not depend linearly, but quadratically on the concentration of active ATP synthases. The observed proportional relationships between inhibition of the primary or secondary pump and the inhibition of the overall energy-transfer reactions do not support the existence of a pool intermediate in energy-transduction reactions. However, the results are consistent with a direct transfer of energy from redox enzymes to ATP synthase and vice versa.
...
PMID:Inhibition of energy-transducing reactions by 8-nitreno-ATP covalently bound to bovine heart submitochondrial particles: direct interaction between ATPase and redox enzymes. 286 15

The Mg2+-ATPase activities of bovine adrenal chromaffin granules were studied in highly purified preparations of granule ghosts and in intact organelles. The overall ATPase activity (150-250 nmol ADP min-1 mg-1) of the granule ghost preparations was inhibited less than 5% by the bathophenanthroline chelate of Fe(II), a potent inhibitor of mitochondrial F1-ATPase. This small inhibition can be accounted for by a very minor contamination with mitochondria or mitochondrial fragments. The overall ATPase activity of native granule ghosts was inhibited about 75% by N-ethylmaleimide, with half-maximal inhibition at about 20 microM. The titration curve was slightly shifted towards higher concentrations as compared to the inhibition curve for the proton pump activity, which was completely inhibited at 25 microM. N,N'-Dicyclohexylcarbodiimide inhibited the overall ATPase activity by 75-80% at 1.1 mumol/mg protein, a concentration that completely abolished the proton pump activity. Low concentrations (10 microM) of vanadate inhibited the overall ATPase activity by about 15% but had no effect on the proton pump activity, which was partly inhibited only at higher vanadate concentrations. Our attempts to assign a function to the vanadate-sensitive and N-ethylmaleimide-insensitive ATPase have so far been unsuccessful. In particular, our assay for ATP diphosphohydrolase activity was negative, although the chromaffin granule ghosts revealed a low Mg2+-ADPase activity (11.8 nmol AMP min-1 mg-1 protein). In intact chromaffin granules the specific Mg2+-ATPase activity (50-70 nmol ADP min-1 mg-1) was stimulated 2-fold by uncouplers, as compared to 1.6-1.7-fold in granule ghosts. The degree of energy coupling was rather independent of the external pH (6.5 less than pH less than 8.0) and temperature (20-45 degrees C). As expected, partial inhibition (about 15%) of the overall ATPase activity by 10 microM vanadate increased the ATPase control ratio. ADP was found to be a potent inhibitor of the proton pump activity with MgATP as the substrate, and the effect can partly be explained by a competitive type of inhibition of the hydrolytic reaction. This effect of ADP explains some of the kinetic data reported for MgATP-dependent (H+-ATPase-dependent) reactions in this organelle, notably the energy-dependent accumulation and storage of catecholamines.
...
PMID:Studies on Mg2+-dependent ATPase in bovine adrenal chromaffin granules. With special reference to the effect of inhibitors and energy coupling. 288 84

The gap between early molecular evolution and the origin of the first cell may have been bridged by a photoheterotrophic obcell, consisting of genes and ribosomes attached to the outer surface of a phospholipid vesicle containing a light-driven proton pump and a proton-driven pyrophosphate synthase. I argue that the obcell was the substratum for the origin of DNA replication; DNA segregation by the growth and division of the peptidoglycan murein; periplasmic solute-binding proteins; bioenergetics, including the F0F1 proton-driven ATP synthase; active transport of calcium; and facilitated diffusion of nutrients across membranes, and that it played the major role in the replacement of ribozymes by protein catalysts. Curved growth of the peptidoglycan and a mutation causing septum formation produced the first true cell. Evolution of porins, sodium extrusion and potassium import, conversion of the facilitated diffusion proteins to active pumps, and the evolution of intermediary metabolism, carbon and nitrogen fixation, and of substrate level phosphorylation, completed the origin of the first negibacterial eubacterium, from which all other cells evolved, and from which they have inherited most of their major catalytic properties--with the notable exceptions of reverse transcriptase, RNA splicing, and methanogenesis, all of which I believe evolved very much later.
...
PMID:The origin of cells: a symbiosis between genes, catalysts, and membranes. 345 90

The activity of the light-dependent proton pump (in the absence of phosphorylation substrates) of Rhodopseudomonas capsulata "membrane vesicles," in contrast to that of chloroplasts, is not appreciably affected by detachment of phosphorylation coupling factor(s). Proton uptake by such "uncoupled" (low phosphorylation activity) preparations is also unaffected by the addition of phosphorylation substrates (ADP + arsenate + Mg(2+)). The H(+) pump of "coupled" preparations, however, is stimulated when all of the substrates are present simultaneously. Oligomycin appears to affect both photophosphorylation and the H(+) pump by interaction with a component of the energy transfer sequence that is distinct from coupling factor. The results obtained suggest that in photosynthetic bacteria light-dependent cyclic electron flow (the driving force for photophosphorylation) is accelerated by active phosphorylation which, in turn, is dependent on the presence of protein coupling factors in the energy-converting membrane.
...
PMID:Role of phosphorylation coupling factor in light-dependent proton translocation by Rhodopseudomonas capsulata membrane preparations. 500 93

Clathrin-coated vesicles isolated from calf brain contain an ATP-dependent proton pump. Proton movement was monitored by measuring [14C]methylamine distribution. Addition of Mg2+ and ATP to coated vesicles equilibrated with [14C]methylamine resulted in the generation of a 4- to 5-fold concentration gradient, corresponding to a delta pH of 0.6-0.7 units between the medium and the acidic inside of the coated vesicles. ATP-dependent [14C]methylamine uptake was abolished by the proton ionophore carbonylcyanide p-trifluoromethoxyphenylhydrazone (FCCP) and partially inhibited by the carboxyl reagent N,N'-dicyclohexylcarbodiimide but was unaffected by the Na+, K+-ATPase inhibitors strophanthidin (100 microM) and vanadate (10 microM) and the mitochondrial ATPase inhibitors oligomycin (10 microgram/ml) and aurovertin (1 microgram/ml). GTP, but not the nonhydrolyzable analog 5'-adenylyl imidodiphosphate, could support [14C]methylamine uptake. Dissipation of the membrane potential with K+ and valinomycin resulted in stimulation of [14C]methylamine uptake, whereas both FCCP and valinomycin stimulated the strophanthidin-resistant ATPase activity. These results are consistent with the existence of an electrogenic, ATP-dependent proton pump in clathrin-coated vesicles. This proton pump may play a role in the acidification events that are essential in receptor-mediated endocytosis.
...
PMID:Clathrin-coated vesicles contain an ATP-dependent proton pump. 613 17

Cholinergic synaptic vesicles from the electric organ of Torpedo marmorata are associated with a Mg2+-ATPase insensitive to ouabain and oligomycin. Treatment of vesicle membranes with dichloromethane releases a Mg2+-ATPase with apparent molecular mass of around 250 kDa as determined by gel filtration. The vesicular ATPase resembles the mitochondrial F1-ATPase in these properties. Gel electrophoresis of the solubilized ATPase shows however that only a single 50-kDa band is present as compared to the alpha-subunit (52 kDa) and beta-subunit (50 kDa) of electric organ mitochondrial F1-ATPase present in this range of molecular mass range. In agreement, covalent photoaffinity labelling of isolated vesicles with azido-ATP shows a 50-kDa band. Vesicle ghosts were found to accumulate [14C]methylamine in an ATP-dependent manner indicating the presence of an inwardly directed proton pump. We conclude that cholinergic vesicles contain a proton pump probably driven by the Mg2+-ATPase here described, which generates an electrochemical gradient across the vesicle membrane and is necessary for uptake and storage of acetylcholine within the vesicles.
...
PMID:Characterization of a Mg2+-ATPase and a proton pump in cholinergic synaptic vesicles from the electric organ of Torpedo marmorata. 614 23


1 2 3 4 5 Next >>

---