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:2.7.1.1 (hexokinase)
5,274 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel requires both phosphorylation of its R domain and the presence of nucleoside triphosphates for activation. Our previous work suggested that hydrolysis of nucleoside triphosphates may be required to support channel activity. However, recent studies have suggested that the nonhydrolyzable adenosine triphosphate analogue, 5'-adenylylimidodiphosphate (AMP-PNP), may support some Cl- channel activity in sweat gland duct epithelia in the presence of low ATP concentration and in Cl- channels associated with expression of the P-glycoprotein multidrug resistance transporter. To examine the effect of AMP-PNP, we applied it to the cytosolic surface of phosphorylated CFTR Cl- channels contained in excised, cell-free patches of membrane. We found that preparations of 10 mM AMP-PNP opened phosphorylated CFTR Cl- channels. However, this effect was due to contaminating ATP: high-pressure liquid chromatography analysis of AMP-PNP demonstrated that 10 mM AMP-PNP could contain up to 50 microM ATP, which could account for the observed stimulation of CFTR Cl- channel activity. When contaminating ATP was hydrolyzed with hexokinase, AMP-PNP was unable to support CFTR channel activity. AMP-PNP (10 mM) also failed to attenuate or potentiate the current induced by 0.3 mM ATP. These results suggest that AMP-PNP has no direct effect on CFTR Cl- channels.
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PMID:5'-Adenylylimidodiphosphate does not activate CFTR chloride channels in cell-free patches of membrane. 768 26

The energy metabolism was evaluated in gastrocnemius muscle from 3-month-old rats subjected to either mild or severe 4-week intermittent normobaric hypoxia. Furthermore, 4-week treatment with CNS-acting drugs, namely, alpha-adrenergic (delta-yohimbine), vasodilator (papaverine, pinacidil), or oxygen-increasing (almitrine) agents was performed. The muscular concentration of the following metabolites was evaluated: glycogen, glucose, glucose 6-phosphate, pyruvate, lactate, lactate-to-pyruvate ratio; citrate, alpha-ketoglutarate, succinate, malate; aspartate, glutamate, alanine; ammonia; ATP, ADP, AMP, creatine phosphate. Furthermore the Vmax of the following muscular enzymes was evaluated: hexokinase, phosphofructokinase, pyruvate kinase, lactate dehydrogenase; citrate synthase, malate dehydrogenase; total NADH cytochrome c reductase; cytochrome oxidase. The adaptation to chronic intermittent normobaric mild or severe hypoxia induced alterations of the components in the anaerobic glycolytic pathway [as supported by the increased activity of lactate dehydrogenase and/or hexokinase, resulting in the decreased glycolytic substrate concentration consistent with the increased lactate production and lactate-to-pyruvate ratio] and in the mitochondrial mechanism [as supported by the decreased activity of malate dehydrogenase and/or citrate synthase resulting in the decreased concentration of some key components in the tricarboxylic acid cycle]. The effect of the concomitant pharmacological treatment suggests that the action of CNS-acting drugs could be also related to their direct influence on the muscular biochemical mechanisms linked to energy transduction.
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PMID:Modifications by chronic intermittent hypoxia and drug treatment on skeletal muscle metabolism. 778 38

The characteristics of the energy metabolism were evaluated in the gastrocnemius muscle from 3- and 24-month-old rats in normoxia or subjected to either mild or severe chronic (4 weeks) intermittent normobaric hypoxia. Furthermore, 4-week treatment with saline or the TRH-analogue posatireline was performed. The muscular concentration of the following metabolites related to the energy metabolism was evaluated: glycogen, glucose, glucose 6-phosphate, pyruvate, lactate, lactate-to-pyruvate ratio; citrate, alpha-ketoglutarate, succinate, malate; aspartate, glutamate, alanine; ammonia; ATP, ADP, AMP, creatine phosphate; energy charge potential. Furthermore the maximum rate of the following muscular enzymes was evaluated: hexokinase, phosphofructokinase, pyruvate kinase, lactate dehydrogenase; citrate synthase, malate dehydrogenase; total NADH cytochrome c reductase; cytochrome oxidase. The age-related decrease in muscular glucose 6-phosphate, pyruvate and alanine concentrations and increase in citrate concentration were consistent with the age-related decreased hexokinase and increased citrate synthase activities. Ageing was characterized by a decrease in muscular creatine phosphate concentration, while the energy mediators and the energy charge potential were unchanged. The chronic (4 weeks) intermittent normobaric mild and severe hypoxia-induced alterations of the components in the anaerobic glycolytic pathway, tricarboxylic acid cycle and energy storage, that were magnified in the skeletal muscle from the oldest animals. The effect of the chronic treatment with the TRH-analogue posatireline suggests that the action of central nervous system-acting drugs could also be related to their direct influence on the muscular biochemical mechanisms related to the energy transduction.
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PMID:Age-related alterations of skeletal muscle metabolism by intermittent hypoxia and TRH-analogue treatment. 781 45

Twelve isomers formed by the reaction of monoamminechromium(III) with ATP have been synthesized. Isomerism in this system results from chirality around the beta-phosphorus of the ATP, the position of the ammonia ligand, the relative orientation of the ammonia and the AMP, and the presence of ring-puckering conformers. By using chromatography on cross-linked cycloheptaamylose, reverse-phase C-18 HPLC, and cation-exchange FPLC, these isomers have been separated and purified. Their structures have been identified by (1) cleavage by periodate, followed by elimination in the presence of diethylenetriamine and subsequent phosphate insertion to give lambda, delta, or meso facial monoamminechromium tripolyphosphate with molar ellipticities of +240, -240, or 0 deg cm2 dmol-1 at 550 nm, respectively, (2) cleavage by nucleotide pyrophosphatase to give meridional or facial monoamminechromium pyrophosphate, (3) spectral data, and (4) rates of interconversion of isomers. All possible isomers are seen except those with ammonia syn to AMP. Since the substitution of ammonia for water in the inner coordination sphere appears to diminish affinity for enzymes when the ammonia is in contact with the protein but not when it faces the solvent, these isomers are useful for mapping of enzyme active sites. Their use as probes of enzyme structure is illustrated by their behavior with yeast hexokinase.
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PMID:Characterization of isomers of monoamminechromium-ATP and their use in mapping enzyme active sites. 821 84

In the presence of glycogen, ADP, phosphoglucomutase and hexokinase, the glycogen phosphorylase b activity associated to sarcoplasmic reticulum (SR) membranes stimulates Ca2+ uptake by SR membrane fragments in the absence of added ATP. Phosphoglucomutase and hexokinase lead to the formation of glucose 6-phosphate which in turn is used as an ATP regenerating system by the Ca2+ pump. It is proposed that a raise of cytosolic AMP and ADP concentrations after muscle contraction can activate an alternative metabolic route which would be used to ensure the maintenance of a low cytosolic Ca2+ concentration and avoid unnecessary metabolic energy depletion in muscle cells.
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PMID:Glycogen phosphorolysis can form a metabolic shuttle to support Ca2+ uptake by sarcoplasmic reticulum membranes in skeletal muscle. 825 Aug 71

An ATP-diphosphohydrolase (EC 3.6.1.5) was identified in the tegumental fraction isolated from Schistosoma mansoni worms. Both ATP and ADP were hydrolyzed to AMP at similar rates by the enzyme. Other nucleotides were also degraded by the tegument enzyme, revealing a broad substrate specificity. Electrophoretic separation of tegumental proteins under non-denaturing conditions followed by addition of ATP or ADP as substrate revealed a single band of activity with similar mobility. In addition, similar heat-inactivation profiles were obtained for ATPase or ADPase activities, indicating that a single enzyme is responsible for degrading both nucleotides. The enzyme was not inhibited by vanadate, levamisole, tetramisole, ouabain or sodium azide. The ADPase activity was not affected by adenosine (5')-pentaphospho-(5')-adenosine (Ap5A) or by an excess of glucose and hexokinase used as an ATP-trapping system, thus excluding the presence of any significant adenylate kinase activity. The ATP-diphosphohydrolase displayed micromolar affinities for both Mg2+ and Ca2+, and the calcium-activated enzyme was inhibited by millimolar Mg2+. In intact live worms a calcium phosphate precipitate was formed on the outer tegumental surface upon incubation of the worms with either ATP or ADP, indicating the ectolocalization of this enzyme. In addition, ultrastructural histochemical localization of the enzyme was obtained. A distinct deposition of lead phosphate granules on the outer surface of the tegument was observed by electron microscopy, in the presence of either ATP or ADP as substrate. It is suggested that the ATP-diphosphohydrolase could regulate the concentration of purine nucleotides around the parasites and hence enable them to escape the host hemostasis by preventing ADP-induced platelet activation.
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PMID:Characterization and localization of an ATP-diphosphohydrolase on the external surface of the tegument of Schistosoma mansoni. 847 45

The practicality of Tris-HCl buffer for modification of histidine residues by diethylpyrocarbonate (DEPC) was studied using a model protein-hexokinase. It was found that modification was selective at pH 7.5. Conditions for modification of one histidine residue in the protein molecule were specified. In 30 mM Tris-HCl buffer pH 7.5, 10-min interaction of RNA-ligase with 0.3 mM DEPC was accompanied by modification of one histidine residue, as a result of which the ability to form a covalent AMP-RNA-ligase complex decreased 3 times. Modification of two histidine residues of RNA-ligase resulted in a complete loss of the enzyme activity. At increasing DEPC concentration modification affected all of the seven histidine residues of RNA-ligase. The kinetic parameters (Km and V) for the native and modified enzymes were determined and compared.
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PMID:[Modification of RNA ligase histidine residues by diethylpyrocarbonate]. 848 23

Thirteen kits from different suppliers for measurement of creatine kinase activity in human serum according to the IFCC recommendations were analyzed and compared. Concentrations of AMP, ADP, creatine phosphate, glucose, magnesium ion, NADP+, glucose-6-phosphate dehydrogenase, hexokinase and pH were measured in the reagents by various analytical techniques and compared with those recommended b the IFCC. We also compared by regression analysis the results of creatine kinase catalytic concentration obtained in human sera using commercial kits and in-house prepared reagents according tot he IFCC recommendation. Creatine kinase was also measured in a reference material using the different reagents. The overall results of the activity measurements and the composition of the majority of the kits agree well with one another and with the IFCC recommendation. Minor deviations were found in the evaluation of a few kits. One kit yielded creatine kinase activity values that were 17% lower. Results obtained in the reference material measurements showed differences with some kits which were not found using human sera.
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PMID:Comparison of kits for the determination of creatine kinase activity in serum. 854 39

Hexokinases catalyze the phosphorylation of glucose and initiate cellular glucose metabolism. Hexokinase II (HKII) is the principal hexokinase isoform in skeletal muscle, heart, and adipose tissue. Isoproterenol and exogenous cyclic AMP (cAMP) increase HKII gene transcription in L6 myotubes. Various segments of the HKII promoter that direct the expression of the chloramphenicol acetyltransferase reporter gene were transfected into L6 myotubes to identify basal and cAMP response elements. The 5'-flanking region that extends 90 base pairs upstream of the transcription start site includes a CCAAT box and a cAMP response element (CRE); both contribute to basal promoter activity and each provides an independent, maximal response to cAMP. An inverted CCAAT motif, or Y box, located just upstream of the CCAAT box, contributes to basal promoter activity but is not involved in the cAMP response. Homo- and heterodimers composed of the CRE-binding protein and activating transcription factor-1 bind specifically to the CRE. The Y box and the CCAAT box specifically bind the factor NF-Y (also known as CBF).
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PMID:Identification and characterization of basal and cyclic AMP response elements in the promoter of the rat hexokinase II gene. 866 88

The glycogenolytic-sarcoplasmic reticulum complex from rat skeletal muscle accumulates Ca2+ upon stimulation of glycogen phosphorolysis in the absence of added ATP. It is shown that an efficient Ca2+ uptake involves the sequential action of glycogen phosphorylase, phosphoglucomutase and hexokinase, which generate low concentrations of ATP (approximately 1-2 microM) compartmentalized in the immediate vicinity of the sarcoplasmic reticulum Ca2+, Mg(2+)-ATPase (the Ca2+ pump). The Ca2+ uptake supported by glycogenolysis in this subcellular structure is strongly stimulated by micromolar concentrations of AMP, showing that the glycogen phosphorylase associated with this complex is in the dephosphorylated b form. The results point out that the flux through this compartmentalized metabolic pathway should be enhanced in physiological conditions leading to increased AMP concentrations in the sarcoplasm, such as long-lasting contractions and in ischemic muscle.
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PMID:Ca2+ uptake coupled to glycogen phosphorolysis in the glycogenolytic-sarcoplasmic reticulum complex from rat skeletal muscle. 881 99


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