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:3.6.1.3 (ATPase)
65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adenosine diphosphatase (ADPase) activity and ATPase activity were assayed in rat liver mitochondria and outer mitochondrial membrane preparations with [beta-32P]ADP and [gamma-32P]ATP as substrates. Inhibition studies were performed with the mitochondrial ATPase inhibitor oligomycin and the adenine nucleotide transport inhibitor, carboxyatractyloside. Kinetic studies were also performed with the nucleotide thiophosphate analogs adenosine 5'-O-thiophosphate, adenosine 5'-O-(2-thiodiphosphate) and adenosine 5'-O-(3-thiotriphosphate) which can act as inhibitors of phosphohydrolases. It is concluded that part of the apparent ADPase activity of intact mitochondria is mediated via ATPase, presumably in conjunction with adenylate kinase. In addition the outer mitochondrial membrane appears to show a distinct ADPase not attributable to contamination by inner membrane ATPase.
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PMID:Comparison of effects of inhibitors on adenosine triphosphatase and adenosine diphosphatase activities in rat-liver mitochondria. 632 Nov 79

Adenosine diphosphatase (ADPase) activity was studied in rat liver with [beta-32P]ADP as a substrate. Mitochondria and outer mitochondrial membrane fractions were isolated and assayed for ADPase and various marker enzymes. ADPase activity was strikingly reduced when the outer membranes were removed from the mitochondria whether by digitonin treatment or osmotic shock. Addition of the inter-membrane space subfraction to the purified outer membranes resulted in enhanced ADPase activity. Addition of the inter-mitochondrial membrane enzyme adenylate kinase to outer membranes also produced a large stimulation of activity. The ADPase activity could also be reconstituted in vitro with adenylate kinase and either mitoplast ATPase or ouabain-sensitive (Na+ + K+ + Mg2+)-ATPase. Chloroform-released ATPase, however, was not capable of producing an ADPase activity when combined with adenylate kinase. Gel permeation chromatography of Triton-solubilised outer mitochondrial membranes was unable to resolve ADPase activity from contaminating ATPase. These results suggest that the majority of ADPase activity in rat liver mitochondria consists of the coupled activity of adenylate kinase and ATPase.
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PMID:Studies on the nature of adenosine diphosphatase activity from rat liver mitochondria. 632 48

By double isotope pulse-labeling of yeast cells, we determined the kinetics of labeling at 9 degrees C of total mitochondrial membrane, mitochondrial matrix, and cytosolic proteins, the alpha, beta, and gamma subunits of F1 ATPase, and glyceraldehyde-3-phosphate dehydrogenase. We find that none of the mitochondrial proteins show a lag in the incorporation of label compared to cytosolic proteins. These results argue against the existence in the cytosol of large pools of mitochondrial proteins awaiting transport into the organelle. Cycloheximide addition during the pulse stops [35S]methionine incorporation into mitochondrial membrane and cytosolic proteins rapidly (approximately 1 min) and with identical kinetics. Compared to cytosolic protein, however, there is a persistent incorporation of label into mitochondria after a chase with cold methionine (t1/2 approximately 1.5 min at 9 degrees C) which cannot be accounted for solely by chain completion. We conclude that this continued incorporation reflects some transport process in addition to a completion of a round of translation. When cells are labeled during a synchronous "restart" of protein synthesis, where ribosome run-off from mRNA was first induced either by incubating cells for 4 h at 0 degrees C or by treatment with 5 mM aurintricarboxylic acid, the initial rate of incorporation of label into mitochondrial protein now lags behind that of cytosolic proteins. From these results and those in the accompanying report (Ades, I.Z., and Butow, R.A. (1980) J. Biol. Chem. 255, 9918-9924) we propose that the translation of mRNA specific for mitochondrial proteins takes place in the cytoplasm and that at least a portion of the polysomes are then transported and bind to the outer mitochondrial membrane, followed by completion of translation and transfer of the newly synthesized polypeptides into the mitochondria. From a consideration of all of the available data on protein transport into mitochondria in yeast, we conclude that cytoplasmic polysomes bound to the outer mitochondrial membrane function in the transport of proteins into mitochondria by a process not necessarily mutually exclusive of post-translational transport.
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PMID:The transport of proteins into yeast mitochondria. Kinetics and pools. 644 42

Functional integrity of liver cell organelles in rats given the model abrupt cytotoxin 1,1-dichloroethylene (1,1-DCE) was examined by enzymatic histochemistry. Fasted 200-gm. male Sprague-Dawley rats were sacrificed 1, 2, 4, or 6 hours after an oral dose of 200 mg. of 1,1-DCE per kg. (in mineral oil) and 6 hours after 50, 100, or 150 mg. of 1,1-DCE per kg. Cubes of liver were quick frozen for histochemistry. Stage or degree of liver injury was assessed by histology and by measuring serum transaminase activities and liver ion levels. We found both early injury (2 hours following the 200-mg. per kg. dose) and slight injury (6 hours following the 50-mg. per kg. dose) characterized by: increases in liver sodium levels and striking decreases in the central area staining patterns of bile canaliculi membrane Mg++-ATPase, as well as of outer mitochondrial membrane monoamine oxidase and inner mitochondrial membrane succinate dehydrogenase and cytochrome oxidase. As injury progressed with time or increased in severity with dose, aberrations in the levels of other liver cell ions occurred, serum transaminase activities rose, and decreased staining of plasma membrane and mitochondrial membrane components were evident in progressively wider areas around the central vein. Glutathione depletion was panlobular. In contrast, only at later times (4 and 6 hours) and after the larger doses did alterations to functional components of the mitochondrial matrix, endoplasmic reticulum, lysosomes, and cytosol become evident in a narrow area around the central vein, which became necrotic. We consider these later appearing alterations secondary consequences of the midzonal necrosis and sinusoidal congestion produced by 1,1-DCE, whereas the plasma membranes and mitochondrial membranes appear to be primary foci of injury.
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PMID:Histochemical evidence that plasma and mitochondrial membranes are primary foci of hepatocellular injury caused by 1,1-dichloroethylene. 646 95

It is known that the intercalated cell of the renal collecting duct contains, in addition to abundant mitochondria, characteristic spherical or flat vesicles whose cytoplasmic surfaces were decorated with H(+)-ATPase studs. The intimate association of H(+)-ATPase vesicles with mitochondria was often observed. Here, the limiting membrane of the vesicle and the outer mitochondrial membrane were directly connected to each other by H(+)-ATPase studs. Namely, two membranes were bridged by these studs. This feature was especially evident in the case of flat vesicles. These findings indicated the close interplay between these two cell organellae.
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PMID:Intimate association of H(+)-ATPase vesicles with mitochondria in the intercalated cell of the renal collecting duct. 767 13

A 42-kDa plant outer mitochondrial membrane protein, MOM42, has been identified as an essential component of the plant mitochondrial precursor protein translocation apparatus. Immunological cross-reactivity has been detected between antibodies raised against both Neurospora and yeast mitochondrial outer membrane proteins and plant mitochondrial outer membrane proteins. Immunocompetition studies showed that import of precursors to Rieske FeS protein, ATPase su9-DHFR, and the adenine nucleotide transporter was inhibited in the presence of antibody to MOM42. The inhibition of Rieske Fes and su9-DHFR import was greater than that of the adenine nucleotide transporter. The competition studies suggest that the MOM42 is involved in the translocation of bound precursor proteins. The import data and the Western blots suggest that components of the mitochondrial import system are highly conserved.
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PMID:Identification of a 42-kDa plant mitochondrial outer membrane protein, MOM42, involved in the import of precursor proteins into plant mitochondria. 786 20

Possible reasons for retarded intracellular diffusion of ADP were investigated. The isolated skinned cardiac fibers were used to study apparent kinetic parameters for externally added ADP in control of mitochondrial respiration. Participation of myosin-ATPase in binding of ADP within cells as it was supposed earlier (Saks, V.A., Belikova, Yu.O. and Kuznetsov, A.V. (1991) Biochim. Biophys. Acta 1074, 302-311) was completely excluded, since myosin-deprived skinned cardiac fibers ('ghosts') displayed the same kinetic parameters as intact ones (Kmapp for ADP about 300 microM). Significantly lower apparent Km values were obtained for fibers with osmotically disrupted outer mitochondrial membrane (25-35 microM), which was close to that observed for isolated heart mitochondria. The data obtained are in favor of limitation of ADP movement via anion-selective low-conductance porine channels in the outer membrane of mitochondria. It is proposed that the permeability of this membrane is controlled by some unknown intracellular factor(s). In the presence of saturating concentrations of creatine (25 mM) the apparent Km for ADP significantly decreases due to coupling of creatine kinase and oxidative phosphorylation reactions in mitochondria. This coupling is not observed in KCl medium in which mitochondrial creatine kinase is detached from the membrane. It is concluded that in the cells in-vivo ADP movement between cytoplasm and intramitochondrial space is controlled by low-conductivity anion channels in the outer membrane. Thus, the mitochondrial creatine kinase reaction coupled to the adenine nucleotide translocase is an important mechanism in control of oxidative phosphorylation in vivo due to its ability to manifold amplify these very weak ADP signals from cytoplasm.
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PMID:Retarded diffusion of ADP in cardiomyocytes: possible role of mitochondrial outer membrane and creatine kinase in cellular regulation of oxidative phosphorylation. 839 41

Physiologically, a postprandial glucose rise induces metabolic signal sequences that use several steps in common in both the pancreas and peripheral tissues but result in different events due to specialized tissue functions. Glucose transport performed by tissue-specific glucose transporters is, in general, not rate limiting. The next step is phosphorylation of glucose by cell-specific hexokinases. In the beta-cell, glucokinase (or hexokinase IV) is activated upon binding to a pore protein in the outer mitochondrial membrane at contact sites between outer and inner membranes. The same mechanism applies for hexokinase II in skeletal muscle and adipose tissue. The activation of hexokinases depends on a contact site-specific structure of the pore, which is voltage-dependent and influenced by the electric potential of the inner mitochondrial membrane. Mitochondria lacking a membrane potential because of defects in the respiratory chain would thus not be able to increase the glucose-phosphorylating enzyme activity over basal state. Binding and activation of hexokinases to mitochondrial contact sites lead to an acceleration of the formation of both ADP and glucose-6-phosphate (G-6-P). ADP directly enters the mitochondrion and stimulates mitochondrial oxidative phosphorylation. G-6-P is an important intermediate of energy metabolism at the switch position between glycolysis, glycogen synthesis, and the pentose-phosphate shunt. Initiated by blood glucose elevation, mitochondrial oxidative phosphorylation is accelerated in a concerted action coupling glycolysis to mitochondrial metabolism at three different points: first, through NADH transfer to the respiratory chain complex I via the malate/aspartate shuttle; second, by providing FADH2 to complex II through the glycerol-phosphate/dihydroxy-acetone-phosphate cycle; and third, by the action of hexo(gluco)kinases providing ADP for complex V, the ATP synthetase. As cytosolic and mitochondrial isozymes of creatine kinase (CK) are observed in insulinoma cells, the phosphocreatine (CrP) shuttle, working in brain and muscle, may also be involved in signaling glucose-induced insulin secretion in beta-cells. An interplay between the plasma membrane-bound CK and the mitochondrial CK could provide a mechanism to increase ATP locally at the KATP channels, coordinated to the activity of mitochondrial CrP production. Closure of the KATP channels by ATP would lead to an increase of cytosolic and, even more, mitochondrial calcium and finally to insulin secretion. Thus in beta-cells, glucose, via bound glucokinase, stimulates mitochondrial CrP synthesis. The same signaling sequence is used in the opposite direction in muscle during exercise when high ATP turnover increases the creatine level that stimulates mitochondrial ATP synthesis and glucose phosphorylation via hexokinase. Furthermore, this cytosolic/mitochondrial cross-talk is also involved in activation of muscle glycogen synthesis by glucose. The activity of mitochondrially bound hexokinase provides G-6-P and stimulates UTP production through mitochondrial nucleoside diphosphate kinase. Pathophysiologically, there are at least two genetically different forms of diabetes linked to energy metabolism: the first example is one form of maturity-onset diabetes of the young (MODY2), an autosomal dominant disorder caused by point mutations of the glucokinase gene; the second example is several forms of mitochondrial diabetes caused by point and length mutations of the mitochondrial DNA (mtDNA) that encodes several subunits of the respiratory chain complexes. Because the mtDNA is vulnerable and accumulates point and length mutations during aging, it is likely to contribute to the manifestation of some forms of NIDDM.(ABSTRACT TRUNCATED)
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PMID:Mitochondria and diabetes. Genetic, biochemical, and clinical implications of the cellular energy circuit. 854 53

The mathematical model of the compartmentalized energy transfer system in cardiac myocytes presented includes mitochondrial synthesis of ATP by ATP synthase, phosphocreatine production in the coupled mitochondrial creatine kinase reaction, the myofibrillar and cytoplasmic creatine kinase reactions, ATP utilization by actomyosin ATPase during the contraction cycle, and diffusional exchange of metabolites between different compartments. The model was used to calculate the changes in metabolite profiles during the cardiac cycle, metabolite and energy fluxes in different cellular compartments at high workload (corresponding to the rate of oxygen consumption of 46 mu atoms of O.(g wet mass)-1.min-1) under varying conditions of restricted ADP diffusion across mitochondrial outer membrane and creatine kinase isoenzyme "switchoff." In the complete system, restricted diffusion of ADP across the outer mitochondrial membrane stabilizes phosphocreatine production in cardiac mitochondria and increases the role of the phosphocreatine shuttle in energy transport and respiration regulation. Selective inhibition of myoplasmic or mitochondrial creatine kinase (modeling the experiments with transgenic animals) results in "takeover" of their function by another, active creatine kinase isoenzyme. This mathematical modeling also shows that assumption of the creatine kinase equilibrium in the cell may only be a very rough approximation to the reality at increased workload. The mathematical model developed can be used as a basis for further quantitative analyses of energy fluxes in the cell and their regulation, particularly by adding modules for adenylate kinase, the glycolytic system, and other reactions of energy metabolism of the cell.
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PMID:Compartmentalized energy transfer in cardiomyocytes: use of mathematical modeling for analysis of in vivo regulation of respiration. 919 6

The role of cytosolic factors in protein targeting to mitochondria is poorly understood. Here, we show that in mammals, the cytosolic chaperones Hsp90 and Hsp70 dock onto a specialized TPR domain in the import receptor Tom70 at the outer mitochondrial membrane. This interaction serves to deliver a set of preproteins to the receptor for subsequent membrane translocation dependent on the Hsp90 ATPase. Disruption of the chaperone/Tom70 recognition inhibits the import of these preproteins into mitochondria. In yeast, Hsp70 rather than Hsp90 is used in import, and Hsp70 docking is required for the formation of a productive preprotein/Tom70 complex. We outline a novel mechanism in which chaperones are recruited for a specific targeting event by a membrane-bound receptor.
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PMID:Molecular chaperones Hsp90 and Hsp70 deliver preproteins to the mitochondrial import receptor Tom70. 1252 92


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