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

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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)

The mitochondrial ATPase inhibitor proteins--the Pullman-Monroy inhibitor (PMI) and the Ca(2+)-binding protein (CaBI)--have a wide distribution, both being present in mitochondria of bovine heart and kidney, rat liver and brain, two mitochondrial populations of rabbit skeletal muscle, and mitochondria from human fibroblasts and the human breast cancer cell line T-47-D. The ratio of CaBI to PMI was highest in heart and skeletal muscle mitochondria. The subsarcolemmal fraction of skeletal muscle had 2.6-times as much CaBI as did the intermyofibrillar. The ratio of CaBI to PMI in the mitochondria of the other normal tissues and fibroblasts was close to 1. In contrast, mitochondria from T-47D cells had 1.5-times as much PMI as CaBI whilst mitochondria from fibroblasts from a patient with Luft's disease showed a virtual lack of PMI. The specific ATPase, ATP-synthetase and succinate dehydrogenase activities of the Luft's mitochondria were, however, in the normal range. The specific ATP synthetase activity of the T-47D cells was significantly higher than normal. We conclude that tissues like heart and skeletal muscle which experience wide fluctuations in intracellular Ca2+ have a greater need for CaBI. Why lack of PMI could lead to 'loose' coupling of oxidative phosphorylation in skeletal muscle of Luft's patients, but not in fibroblasts is discussed.
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PMID:Distribution of the ATPase inhibitor proteins of mitochondria in mammalian tissues including fibroblasts from a patient with Luft's disease. 153 26

We have seen that there is no simple answer to the question 'what controls respiration?' The answer varies with (a) the size of the system examined (mitochondria, cell or organ), (b) the conditions (rate of ATP use, level of hormonal stimulation), and (c) the particular organ examined. Of the various theories of control of respiration outlined in the introduction the ideas of Chance & Williams (1955, 1956) give the basic mechanism of how respiration is regulated. Increased ATP usage can cause increased respiration and ATP synthesis by mass action in all the main tissues. Superimposed on this basic mechanism is calcium control of matrix dehydrogenases (at least in heart and liver), and possibly also of the respiratory chain (at least in liver) and ATP synthase (at least in heart). In many tissues calcium also stimulates ATP usage directly; thus calcium may stimulate energy metabolism at (at least) four possible sites, the importance of each regulation varying with tissue. Regulation of multiple sites may occur (from a teleological point of view) because: (a) energy metabolism is branched and thus proportionate regulation of branches is required in order to maintain constant fluxes to branches (e.g. to proton leak or different ATP uses); and/or (b) control over fluxes is shared by a number of reactions, so that large increases in flux requires stimulation at multiple sites because each site has relatively little control. Control may be distributed throughout energy metabolism, possibly due to the necessity of minimizing cell protein levels (see Brown, 1991). The idea that energy metabolism is regulated by energy charge (as proposed by Atkinson, 1968, 1977) is misleading in mammals. Neither mitochondrial ATP synthesis nor cellular ATP usage is a unique function of energy charge as AMP is not a significant regulator (see for example Erecinska et al., 1977). The near-equilibrium hypothesis of Klingenberg (1961) and Erecinska & Wilson (1982) is partially correct in that oxidative phosphorylation is often close to equilibrium (apart from cytochrome oxidase) and as a consequence respiration and ATP synthesis are mainly regulated by (a) the phosphorylation potential, and (b) the NADH/NAD+ ratio. However, oxidative phosphorylation is not always close to equilibrium, at least in isolated mitochondria, and relative proximity to equilibrium does not prevent the respiratory chain, the proton leak, the ATP synthase and ANC having significant control over the fluxes. Thus in some conditions respiration rate correlates better with [ADP] than with phosphorylation potential, and may be relatively insensitive to mitochondrial NADH/NAD+ ratio.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Control of respiration and ATP synthesis in mammalian mitochondria and cells. 159 89

STUDY OBJECTIVE - The aim of the study was to measure variations in ATP synthase capacity in cultured cardiomyocytes under conditions of metabolic stimulation. DESIGN - ATP synthase activity was measured in cultured rat cardiomyocytes using a procedure which allowed rapid measurement of mitochondrial function during changes in metabolic state. EXPERIMENTAL MATERIAL - Calcium tolerant cardiomyocytes were prepared from male Wistar rats, weight 250-300 g, n = 6-22 per experiment. MEASUREMENTS AND MAIN RESULTS - Electrical stimulation of cardiomyocytes led to an approximate doubling of ATP synthase capacity within 1-2 min, and was rapidly reversible. Activation was reduced when extracellular calcium was lowered and abolished in presence of the calcium entry blocker ruthenium red. Exposure of cardiomyocytes to isoprenaline or to an inhibitor of phosphodiesterase III also led to a large increase in ATP synthase capacity, which was abolished in presence of ruthenium red. However, the response of cells to isoprenaline depended on their pretreatment: activation of ATP synthase was abolished after 20 min anoxia prior to isoprenaline treatment but regained after a subsequent 30 min reoxygenation. This may reflect down regulation of beta receptors on the cell surface during anoxia. CONCLUSIONS - ATP synthase is directly controlled in vivo by a non-allosteric mechanism. Activation of ATP synthase is a response to intramitochondrial Ca2+ concentration.
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PMID:Control of mitochondrial ATP synthase in heart cells: inactive to active transitions caused by beating or positive inotropic agents. 169 47

The flux control distribution of the net rate of state 3 respiration was determined in heart and kidney mitochondria incubated with low concentrations of pyruvate (0.5 mM) or 2-oxoglutarate (1 mM), and in conditions that led to activation of NAD-linked dehydrogenases, i.e., high substrate or Ca2+ concentrations. Control of flux was exerted by the ATP/ADP carrier (flux control coefficient, ci = 0.37) and Site 1 of the respiratory chain (ci = 0.28) when dehydrogenase activity was low. Control of the process shifted to the ATP synthase (ci = 0.32) and the Pi carrier (Ci = 0.27) when dehydrogenases were activated by high pyruvate and high Ca2+. The changes in the control exerted by the ATP/ADP carrier and the ATP synthase were not due to changes in the transmembrane potential, nor to a modification of intramitochondrial ATP/ADP ratios. Applying the summation theorem of the control analysis, it was found that at low Ca2+ and pyruvate concentrations the dehydrogenases shared the control of state 3 respiration with other steps. The NAD-linked dehydrogenases did not exert any significant control at high Ca2+ or high pyruvate concentrations.
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PMID:Distribution of control of oxidative phosphorylation in mitochondria oxidizing NAD-linked substrates. 175 13

Rotenone-sensitive, uncoupler-insensitive, NADH-dependent respiration was demonstrated in osmotically inactive fragments of the mitochondrial inner-membrane obtained following high amplitude (spontaneous) swelling. This NADH-dependent respiration as well as mitochondrial ATPase activity was stimulated by ligands which are known to be transported by specific transporters/mechanisms. The ligands capable of this anomalous respiratory control included several intermediates of the citric acid cycle, besides non-metabolizable ligands including lactate, cations such as K+ and Ca2+. The interaction between NADH-dependent respiration and these ligands, as manifested by stimulation of respiration, was strongly ionic strength-dependent. The thermodynamic relationship between respiratory control and stimulation of transport ATPase by the relevant transportable ligands could also be demonstrated in the conventional (rat liver) microsomes. These experimental results offer a novel experimental base for search into an intra-membranous mechanism of energy transduction.
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PMID:NADH-dependent respiration in osmotically inactive swollen mitochondria: does transport replace phosphorylation in mediating respiratory control in swollen mitochondria? 175 31

Activities of the mitochondrial ATP synthase and the electron transfer chain were investigated in cultured cardiomyocytes prepared from untreated and thyroxine-treated rats. Quiescent cells from the thyroxine-treated animals showed a 33% increase in mitochondrial ATP synthase capacity, but no change in respiratory chain capacity, relative to those from control animals. This increase was attributable largely to (a) a 25% increase in F1 content in these mitochondria, and partly to (b) a 10% stimulation in ATPase activity due to raised intramitochondrial Ca2+. Both types of cell showed a normal ATP content of 38-40 nmol/mg cell protein. In control cells, the mitochondrial ATP synthase responded to increased energy demand (by electrical stimulation and/or by positive inotropic agents) with an increase in its capacity of up to 2-fold. This response was absent in cells from thyroxine-treated animals. In addition, cellular ATP levels fell significantly after 2 min electrical stimulation of cells from thyroxine-treated animals, while those of control cells were constant. It was concluded that regulation of the mitochondrial ATP synthase was defective in heart cells from thyroxine treated rats, leading to an energy deficit when energy demand on the cells was increased. Animals treated with thyroxine, but allowed to recover for 17 days after treatment, showed responses indistinguishable from the control cells. Thus, the effects of thyroxine on mitochondrial activities were reversible.
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PMID:Control of mitochondrial ATP synthase in rat cardiomyocytes: effects of thyroid hormone. 182 41

The F1 complex of the ATP synthase of Streptomyces lividans was isolated and purified. The procedure involved the solubilization of F1 from membranes with buffer of low ionic strength in the presence of EDTA, ion-exchange chromatography and gel filtration. The purified F1 complex from S. lividans (SLF1) consists of five subunits alpha, beta, gamma, delta and epsilon with molecular masses of 58,000, 50,000, 36,000, 28,000 and 13,000, respectively and exhibits immunological cross-reactivity with the F1 portion purified from Escherichia coli (ECF1). The enzymatic properties of SLF1 were determined by the use of microtiter-plate-based assay and compared with data obtained for ECF1. ATPase activity of SLF1 (specific activity: 20-30 U/mg) was only observed in the presence of high concentrations of Ca2+ (10mM). Stimulation of the ATPase activity by Mg2+ was not detectable; quite to the contrary, Mg2+ inhibited the Ca(2+)-stimulated activity of SLF1. SLF1 was re-bound to F1-stripped membranes of S. lividans, but not to F1-stripped membrane vesicles of E. coli. In contrast, ECF1 could be cross-reconstituted with F1-stripped membranes of S. lividans; however, a structural but not a functional reconstitution of the hybrid F1Fo complex was observed.
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PMID:Purification and characterization of the F1 portion of the ATP synthase (F1Fo) of Streptomyces lividans. 183 70

In order to understand the role of carnitine metabolites in the genesis of cellular dysfunction and damage due to myocardial ischemia, the effects of 1-100 microM L-carnitine, acetylcarnitine, propionylcarnitine, and palmitoylcarnitine were investigated on rat heart sarcolemmal, sarcoplasmic reticular, and mitochondrial ATPase activities. Palmitoylcarnitine, unlike acetylcarnitine, propionylcarnitine and carnitine, produced marked inhibitory actions on sarcolemmal Na,K-ATPase and Ca2(+)-stimulated ATPase, as well as sarcoplasmic reticular Ca2(+)-stimulated ATPase activities; Na,K-ATPase was most sensitive. Although palmitoylcarnitine, unlike carnitine or its short-chain fatty-acid derivatives, also depressed sarcolemmal Ca2+ ATPase or Mg2+ ATPase, sarcoplasmic reticular Mg2+ ATPase, and mitochondrial Mg2+ ATPase, mitochondria were less sensitive in comparison to other organelles. Myofibrillar Ca2(+)-stimulated ATPase was slightly inhibited by very high concentrations of palmitoylcarnitine only. It is suggested that the observed depression of the sarcolemmal Na(+)-pump system by low concentrations of long-chain acyl derivatives of carnitine may contribute towards the pathogenesis of arrhythmias due to myocardial ischemia. Furthermore, the inhibition of Ca2(+)-pump mechanisms in the sarcolemmal and sarcoplasmic reticular membranes by relatively high concentrations of palmitoylcarnitine may result in the occurrence of intracellular Ca2+ overload and subsequent cell damage, as well as cardiac dysfunction due to myocardial ischemia.
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PMID:Effects of some L-carnitine derivatives on heart membrane ATPases. 185 32

Among several bioactive substances known as coupling factors, transforming growth factor-beta (TGF-beta), interleukin-1 (IL-1), and prostaglandin (PG) E1 and E2 increased not only the activity of alkaline phosphatase but also the rate of incorporation of 45Ca2+ into ROS 17/2.8 during a 3-day culture: the former two factors are known to be formed at the site where bone is resorbed, while PG's are known as one of the factors involved in bone resorption. Parathyroid hormone, another hormone that affects bone metabolism, elevated the incorporation of 45Ca2+ by and decreased the alkaline phosphatase activity of the cells. The facts indicate the possibility that the osteoblastic cells are involved in the transport of calcium ions when bones are being resorbed. On the other hand, when these osteosarcoma cells were cultured in DMEM containing ascorbate and beta-glycerophosphate, followed by staining with silver nitrate by the procedure of von Kossa, there appeared many groups of cells that were positively stained as dark brown spots. Cells were then cultured under the same conditions in the presence of radioactive calcium, and the radioactivity accumulated was measured. The result showed that the presence of both ascorbate and beta-glycerophosphate in the culture medium dramatically increased the accumulation of 45Ca2+. It appears from these facts that ROS 17/2.8 cells are capable of incorporating and/or accumulating calcium ion if they are cultured under appropriate conditions. These cells will probably be able to produce a calcified matrix in vitro.
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PMID:[Effects of L-ascorbic acid and bone metabolism factors on alkaline phosphatase activity of and 45Ca2+ incorporation by ROS 17/2.8 cells]. 213 81

An ATPase from anaerobic Lactobacillus casei has been isolated and 100-times purified. The 400 kDa enzyme molecule was found to have a hexagonal structure 10 nm in diameter composed of at least six protein masses. SDS-electrophoresis reveals four or, under certain conditions, five types of subunit, of apparent molecular masses 57 (alpha), 55 (beta), 40 (gamma), 22 (delta) and 14 (epsilon) kDa with stoichiometry of 3 alpha, 3 beta, gamma, delta, epsilon. The following features resembling F1-ATPases from other sources were found to be inherent in the solubilized L. casei ATPase. (i) Detachment from the membrane desensitizes ATPase to low DCCD concentrations and sensitizes it to water-soluble carbodiimide. (ii) Soluble ATPase is inhibited by Nbf chloride and azide, is resistant to SH-modifiers and is activated by sulfite and octyl glucoside, the activating effect being much stronger than in the case of the membrane-bound ATPase. Substrate specificity of the enzyme is also similar to that of other factors F1. Divalent cations strongly activate the soluble enzyme when added at a concentration equal to that of ATP. An excess of Mn2+, Mg2+ or Co2+ inhibits ATPase activity of F1, whereas that of Ca2+ induces its further activation. No other F1-like ATPases are found in L. casei. It is concluded that this anaerobic bacterium possesses a typical F1-ATPase similar to those in mitochondria, chloroplasts, aerobic and photosynthetic eubacteria.
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PMID:The F1-type ATPase in anaerobic Lactobacillus casei. 213 82


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