Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20020 (adenosine triphosphatase)
 3,299 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this work was to test the previously suggested hypothesis that the inhibitory effect of ouabain on lactate production in human red cells is due to an interaction between phosphoglycerate kinase and (Na+ + k+)-activated adenosine triphosphatase (Na+,K+ATPase). An antibody to red cell phosphoglycerate kingase caused complete inhibition of the purified enzyme, whereas a portion of the phophoglycerate kinase activity of the red cell membranes was resistant to the antibody. When increasing amounts of the purified enzyme were added to the membranes, the antibody-resistant portion of the activity increased. The effects of the antibody and ouabain on lactate production from fructose-6,6-diphosphate in red cell hemolysates were studied. Ouabain, at a maximally effective concentration, produced about 30% inhibition of lactate formation. This value was doubled in the presence of the antibody. Red cell membranes, and rat brain Na+,K+-ATPase, did not catalyze the hydrolysis of 1,3-diphosphoglycerate. Ouabain did not affect the reactions of the Rapport-Luebering pathway of the red cells. These findings provide further support for the view that in red cells a membrane pool of phosphoglycerate kinase is oriented in the vicinity of Na+,K+-ATPase in a way that the product of each enzyme may be used as the immediate substrate of the other and that ouabain inhibits glycolysis by removing the regulatory effect of Na+,K+-ATPase on that portion of glycolysis which is channeled through this pool of phosphoglycerate kinase.
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PMID:Studies on the mechanism of inhibition of the red cell metabolism by cardiac glycosides. 12 26

Space-filling models of yeast hexokinase, adenylate kinase, and phosphoglycerate kinase drawn by computer clearly portray the bilobal character of these phosphoryl transfer enzymes, and the deep cleft which is formed between the lobes. A dramatic conformational change occurs in hexokinase as glucose binds to the bottom of the cleft, which causes the two lobes of hexokinase to come together. A substrate-induced closing of the active site cleft is postulated to occur in other kinases as well. This change may provide a mechanism by which some of these enzymes reduce their inherent adenosine triphosphatase activity and could be a general requirement of the kinase reaction.
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PMID:Space-filling models of kinase clefts and conformation changes. 22 Jul 6

1. Intracellular concentrations of intermediates and cofactors of glycolysis were measured in guinea-pig cerebral cortex slices incubated under varying conditions. 2. Comparison of mass-action ratios with apparent equilibrium constants for the reactions of glycolysis showed that hexokinase, phosphofructokinase and pyruvate kinase catalyse reactions generally far from equilibrium, whereas phosphoglucose isomerase, aldolase, phosphoglycerate kinase, phosphoglycerate mutase, enolase, adenlyate kinase and creatine phosphokinase are generally close to equilibrium. The possibility that glyceraldehyde 3-phosphate dehydrogenase may catalyse a ;non-equilibrium' reaction is discussed. 3. Correlation of changes in concentrations of substrates for enzymes catalysing ;non-equilibrium' reactions with changes in rates of glycolysis caused by alteration of the conditions of incubation showed that hexokinase, phosphofructokinase, pyruvate kinase and possibly glyceraldehyde 3-phosphate dehydrogenase are subject to metabolic control in cerebral cortex slices. 4. It is suggested that the glycolysis is controlled by two regulatory systems, the hexokinase-phosphofructokinase system and the glyceraldehyde 3-phosphate dehydrogenase-pyruvate kinase system. These are discussed. 5. It is concluded that the rate of glycolysis in guinea-pig cerebral cortex slices is limited either by the rate of glucose entry into the slices or by the hexokinase-phosphofructokinase system. 6. It is concluded that addition of 0.1mm-ouabain to guinea-pig cerebral cortex slices causes inhibition of either glyceraldehyde 3-phosphate dehydrogenase or phosphoglycerate kinase or both, in a manner independent of the known action of ouabain on the sodium- and potassium-activated adenosine triphosphatase.
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PMID:Control of glycolysis in cerebral cortex slices. 422 84

Transient kinetic studies of Mg(2+)-dependent heavy-meromyosin ATPase (adenosine triphosphatase) were done by monitoring the release of both ADP and P(i) into the reaction medium by using linked assay systems. The release of P(i) was monitored by its quantitative transfer to ADP, with concomitant reduction of NAD(+) in the presence of d-glyceraldehyde 3-phosphate, d-glyceraldehyde 3-phosphate dehydrogenase and phosphoglycerate kinase. The dissociation rates of the products, ADP and P(i), from heavy meromyosin were shown to be faster than the rate-controlling process, which occurs after the initial bond cleavage of ATP. The chromophoric ATP analogue, 6-mercapto-9-beta-d-ribofuranosylpurine 5'-triphosphate (thioATP) was used as a substrate and spectral changes associated with a single turnover of heavy meromyosin could be assigned to elementary processes of the mechanism. It was shown that the dissociation rate of thioADP was not the rate-controlling process of the thioATPase, whose catalytic-centre activity was 7.6 times that of the ATPase at pH8. The dissociation rate of ADP from heavy meromyosin was measured by using thioATP as displacing agent and was found to be 2.3s(-1), which is about 50 times the catalytic-centre activity of the ATPase at pH8. Transient kinetic studies with chromophoric adenosine phosphate analogues have general application for kinases and ATPases both in characterizing the chemical states of the intermediates and in delineating the elementary processes of the enzyme mechanism.
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PMID:Elementary processes of the magnesium ion-dependent adenosine triphosphatase activity of heavy meromyosin. A transient kinetic approach to the study of kinases and adenosine triphosphatases and a colorimetric inorganic phosphate assay in situ. 426 38

The rate coefficient for (22)Na release from previously labeled human erythrocytes was determined in the presence of 0.1-10 mM sodium fluoride (F). The oxidized nicotinamide adenine dinucleotide (NAD(+)) level at the end of 2 hr of incubation in tris(hydroxymethyl)aminomethane (Tris)-Ringer medium was also measured. Both parameters decreased proportionately as F concentration was raised. Both F-induced changes were immediate and were reversed by 10 mM pyruvate. The decrease in NAD(+) concentration following enolase inhibition by F is attributed to a diminished rate of formation in the reaction catalyzed by lactic dehydrogenase (LDH) with undiminished continued utilization in the reaction catalyzed by glyceraldehyde-3-phosphate dehydrogenase (GAPDH). It is postulated that the NAD(+) lowering limited the GAPDH step, resulting in proportionate decreases in the rates of phosphoglycerate kinase (PGK) and Na,K-dependent adenosine triphosphatase (Na,K-ATPase), a reaction sequence thought to link glycolysis with active Na extrusion. Adding pyruvate with F increased NAD(+) production at the LDH step, thus reactivating GAPDH, PGK, and Na,K-ATPase and leading to the observed restoration of (22)Na release. The results suggest, therefore, that F inhibits active Na transport in intact human erythrocytes indirectly through a lowering of NAD(+), although, direct inhibition of the Na,K-ATPase by F may possibly occur simultaneously.
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PMID:The role of oxidized nicotinamide adenine dinucleotide in fluoride inhibition of active sodium transport in human erythrocytes. 434 51