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)

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 results of Section IV can be summarized in a simple ATP synthase model. This model implies that either the alpha or the beta subunits must be closer to the membrane. The work of Gao and Bauerlein (1987) indicates that the alpha subunits are closer to the membrane. Although the overall structure is more or less clear, important questions need to be clarified. First, the number and the arrangement of the subunits in the F0 part must be known. Second, the exact shape of F1, and particularly the shape of the large subunits needs to be elucidated. On the basis of fluorescence resonance energy transfer measurements by McCarty and Hammes (1987), a model was presented showing large oblong subunits. Such 'banana-shaped' subunits, which are also presented in the many phantasy models (e.g. Walker et al., 1982), are very unlikely in view of the electron microscopical results, although the large subunits do not need to be exactly spherical. The third and most interesting central question is on the changes in the structure that take place during the different steps in the synthesis of ATP. It can now be taken as proven that the energy transmitted to the ATP synthase is used to induce a conformational change in the latter enzyme, in such a way as to bring about the energy-requiring dissociation of already synthesized ATP (Penefsky, 1985 and reviewed in Slater, 1987). But the way in which the three parts of the ATP synthase are involved is completely unknown. It is rather puzzling that such a long distance exists between the catalytic sites, which are on the interface of the alpha and beta subunits and the F0 part where the proton movements occur, which, according to Mitchell's theory (1961), is the driving force for the synthesis of ATP. Perhaps alternative mechanisms such as the collision hypothesis formulated by Herweijer et al. (1985) are more realistic in describing the mechanism of ATP synthesis. It would bring the complexes I and V close together, not only in the artificial way treated in this paper, but in a useful way for energy conversion.
...
PMID:Electron microscopy and image analysis of the complexes I and V of the mitochondrial respiratory chain. 290 40

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 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

This article reviews proton intake, charge transfer and proton release by F-ATPases, based in part on flash spectrophotometric studies on the chloroplast ATPase in thylakoid membranes, CF1Fo. The synthesis-coupled translocation of charges by CF1Fo (maximum rate <1500 s-1) and the dissipative flow through its exposed channel portion, CFo (rate >10 000 s-1), are extremely proton-specific (selectivity H+:K+>10(7):1). The proton-specific filter is located in CFo. Proton flow through exposed CFo can be throttled by adding subunit (&dgr;) or subunit &bgr; of CF1. These subunits thus may provide energy-transducing contacts between CF1 and CFo. Recently, we characterized two conditions where, in contrast to the above situation, proton intake by CF1Fo was decoupled from proton transfer across the main dielectric barrier: (a) CF1Fo structurally distorted by low ionic strength transiently trapped protons in a highly cooperative manner, but remained proton tight. This result has been interpreted in terms of Mitchell's proton well. (b) In the absence of nucleotides there is a proton slip. Addition of nucleotides (100 nmol l-1 ADP) abolished proton conduction but not proton intake by CF1Fo. These experiments functionally tag proton binding groups on CF1Fo that are located before the main dielectric barrier.
...
PMID:THE CHLOROPLAST H+-ATPase: PARTIAL REACTIONS OF THE PROTON. 987 56

Since the chemiosmotic theory was proposed by Peter Mitchell in the 1960s, a major objective has been to elucidate the mechanism of coupling of the transmembrane proton motive force, created by respiration or photosynthesis, to the synthesis of ATP from ADP and inorganic phosphate. Recently, significant progress has been made towards establishing the complete structure of ATP synthase and revealing its mechanism. The X-ray structure of the F(1) catalytic domain has been completed and an electron density map of the F(1)-c(10) subcomplex has provided a glimpse of the motor in the membrane domain. Direct microscopic observation of rotation has been extended to F(1)-ATPase and F(1)F(o)-ATPase complexes.
...
PMID:The rotary mechanism of ATP synthase. 1111 4

Mitchell's (Mitchell, P. (1961) Nature 191, 144-148) chemiosmotic model of energy coupling posits a bulk electrochemical proton gradient (Deltap) as the sole driving force for proton-coupled ATP synthesis via oxidative phosphorylation (OXPHOS) and for other bioenergetic work. Two properties of proton-coupled OXPHOS by alkaliphilic Bacillus species pose a challenge to this tenet: robust ATP synthesis at pH 10.5 that does not correlate with the magnitude of the Deltap and the failure of artificially imposed potentials to substitute for respiration-generated potentials in energizing ATP synthesis at high pH (Krulwich, T. (1995) Mol. Microbiol. 15, 403-410). Here we show that these properties, in alkaliphilic Bacillus pseudofirmus OF4, depend upon alkaliphile-specific features in the proton pathway through the a- and c-subunits of ATP synthase. Site-directed changes were made in six such features to the corresponding sequence in Bacillus megaterium, which reflects the consensus sequence for non-alkaliphilic Bacillus. Five of the six single mutants assembled an active ATPase/ATP synthase, and four of these mutants exhibited a specific defect in non-fermentative growth at high pH. Most of these mutants lost the ability to generate the high phosphorylation potentials at low bulk Deltap that are characteristic of alkaliphiles. The aLys(180) and aGly(212) residues that are predicted to be in the proton uptake pathway of the a-subunit were specifically implicated in pH-dependent restriction of proton flux through the ATP synthase to and from the bulk phase. The evidence included greatly enhanced ATP synthesis in response to an artificially imposed potential at high pH. The findings demonstrate that the ATP synthase of extreme alkaliphiles has special features that are required for non-fermentative growth and OXPHOS at high pH.
...
PMID:Replacement of amino acid sequence features of a- and c-subunits of ATP synthases of Alkaliphilic Bacillus with the Bacillus consensus sequence results in defective oxidative phosphorylation and non-fermentative growth at pH 10.5. 1502 7

Photophosphorylation was discovered in chloroplasts by D. Arnon and coworkers, and in bacterial 'chromatophores' (intercytoplasmic membranes) by A. Frenkel. Initial low rates were amplified by adding electron-carrying compounds such as FMN, later shown to support the 'pseudocyclic' electron flow. ATP synthesis, and coupling to electron flow, was detected accompanying linear electron flow from H(2)O to either NADP(+) or ferricyanide. Another pattern of electron flow supporting photophosphorylation was that of a cycle around Photosystem I (PS I). Isolation and analysis of the ATP synthase showed, as with mitochondrial and bacterial analogues, an intrinsic membrane complex (CF(0)) and an extrinsic complex (CF(1)). CF(1) is a latent ATPase, activated additively by the high-energy state of the thylakoids, and by reduction of a disulfide bond on the gamma subunit. Once reduced, ATP synthesis occurs at lower energy levels. The search for an 'intermediate' linking electron flow and ATP synthesis led to the discovery of post-illumination ATP synthesis by thylakoids, where turnover occurs in the dark. Once interpreted by P.Mitchell's chemiosmotic hypothesis, this led to the discovery of light-driven proton uptake into the thylakoid lumen, with accompanying Cl(-) intake and Mg(2+) and K(+) output. Chemiosmosis was confirmed in several ways, including ATP synthesis in the dark due to an acid-to-base transition of thylakoids, and photophosphorylation accomplished in artificial lipid vesicles containing both the proton-pumping bacterial rhodopsin and a mitochondrial ATPase complex. The now generally accepted chemiosmotic interpretation is able to clarify some other aspects of photosynthesis as well.
...
PMID:Photophosphorylation and the chemiosmotic perspective. 1624 26

The concept of the membrane proton well was suggested by Peter Mitchell to account for the energetic equivalence of the chemical (DeltapH) and electrical (Deltapsi) components of the proton-motive force. The proton well was defined as a proton-conducting crevice passing down into the membrane dielectric and able to accumulate protons in response to the generation either of Deltapsi or of DeltapH. In this review, the concept of proton well is contrasted to the desolvation penalty of > 500 meV for transferring protons into the membrane core. The magnitude of the desolvation penalty argues against deep proton wells in the energy-transducing enzymes. The shallow DeltapH- and Deltapsi-sensitive proton traps, mechanistically linked to the functional groups in the membrane interior, seem more realistic. In such constructs, the draw of a trapped proton into the membrane core can happen at the expense of some exergonic reaction, e.g., release of another proton from the membrane into the aqueous phase. It is argued that the proton transfer in the ATP synthase and the cytochrome bc complex could proceed in this way.
...
PMID:Proton in the well and through the desolvation barrier. 1678 Jul 89

Thirty years after Peter Mitchell was awarded the Nobel Prize for the chemiosmotic hypothesis, which links the mitochondrial membrane potential generated by the proton pumps of the electron transport chain to ATP production by ATP synthase, the molecular players involved once again attract attention. This is so because medical research increasingly recognizes mitochondrial dysfunction as a major factor in the pathology of numerous human diseases, including diabetes, cancer, neurodegenerative diseases, and ischemia reperfusion injury. We propose a model linking mitochondrial oxidative phosphorylation (OxPhos) to human disease, through a lack of energy, excessive free radical production, or a combination of both. We discuss the regulation of OxPhos by cell signaling pathways as a main regulatory mechanism in higher organisms, which in turn determines the magnitude of the mitochondrial membrane potential: if too low, ATP production cannot meet demand, and if too high, free radicals are produced. This model is presented in light of the recently emerging understanding of mechanisms that regulate mammalian cytochrome c oxidase and its substrate cytochrome c as representative enzymes for the entire OxPhos system.
...
PMID:Regulation of oxidative phosphorylation, the mitochondrial membrane potential, and their role in human disease. 1884 28


1 2 3 Next >>

---