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)

It was verified, by n.m.r. and fast-atom-bombardment-m.s. studies, that the C-2 position of 1,5-anhydro-D-fructose, which was prepared by the reaction of immobilized glucose 2-oxidase from Coriolus versicolor (with 1,5-anhydro-D-glucitol), is hydrated to the acetal form in water. The effects of 1,5-anhydro-D-fructose on several glucose-metabolizing enzymes were compared with those of 1,5-anhydro-D-glucitol. Glucose 1-oxidase from Aspergillus niger was inhibited by 1,5-anhydro-D-fructose (Ki 6.6 mM) more effectively than 1,5-anhydro-D-glucitol (Ki 82.5 mM). Yeast and rat brain hexokinases phosphorylated 1,5-anhydro-D-fructose (Km,yeast 2.3 mM: Km,rat 0.79 mM) and 1,5-anhydro-D-glucitol (Km,yeast 3.9 mM; Km,rat 0.83 mM). The phosphorylated forms of these compounds inhibited D-glucose phosphorylation by yeast hexokinase (Ki of phosphorylated 1,5-anhydro-D-fructose 0.11 mM; Ki of phosphorylated 1,5-anhydro-D-glucitol 0.38 mM) and rat brain hexokinase (Ki of phosphorylated 1,5-anhydro-D-fructose 0.07 mM; Ki of phosphorylated 1,5-anhydro-D-glucitol 0.04 mM). Glucokinase phosphorylated neither 1,5-anhydro-D-fructose nor 1,5-anhydro-D-glucitol, and the phosphorylation of D-glucose by glucokinase was inhibited by them. Mutarotase was slightly inhibited by 1,5-anhydro-D-fructose, as well as by 1,5-anhydro-D-glucitol.
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PMID:Effects of 1,5-anhydro-D-fructose on selected glucose-metabolizing enzymes. 829 6

A Xenopus oocyte expression-co-injection system was used to study the influence of guanine nucleotides on D-glucose uptake. GTP analogs like GTP gamma S and GppNHp had no effect on 3-O-methylglucose transport determined by zero-trans uptake or equilibrium exchange, but suppressed 2-deoxyglucose uptake into Glut1 glucose transporter-expressing oocytes by up to 86%. Both GTP analogs showed concentration dependence of their effectiveness, with GTP gamma S being more potent than GppNHp. No statistically significant differences were observed between groups of oocytes co-injected with water or GDP beta S (250 and 500 microM intracellular concentration). Glut1 transporter expression in plasma membrane was not different between water or GTP gamma S-co-injected oocytes. Thus, inhibition of hexokinase catalytic activity is the most likely causative factor for down-regulation of 2-deoxyglucose uptake.
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PMID:GTP analogs suppress uptake but not transport of D-glucose analogs in Glut1 glucose transporter-expressing Xenopus oocytes. 833 1

The structure of the isocitrate dehydrogenase (IDH) complex with bound alpha-ketoglutarate, Ca2+, and NADPH was solved at 2.7-A resolution. The alpha-ketoglutarate binds in the active site at the same position and orientation as isocitrate, with a difference between the two bound molecules of about 0.8 A. The Ca2+ metal is coordinated by alpha-ketoglutarate, three conserved aspartate residues, and a pair of water molecules. The largest motion in the active site relative to the isocitrate enzyme complex is observed for tyrosine 160, which originally forms a hydrogen bond to the labile carboxyl group of isocitrate and moves to form a new hydrogen bond to Asp 307 in the complex with alpha-ketoglutarate. This triggers a number of significant movements among several short loops and adjoining secondary structural elements in the enzyme, most of which participate in dimer stabilization and formation of the active-site cleft. These rearrangements are similar to the ligand-binding-induced movements observed in globins and insulin and serve as a model for an enzymatic mechanism which involves local shifts of secondary structural elements during turnover, rather than large-scale domain closures or loop transitions induced by substrate binding such as those observed in hexokinase or triosephosphate isomerase.
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PMID:Structure of isocitrate dehydrogenase with alpha-ketoglutarate at 2.7-A resolution: conformational changes induced by decarboxylation of isocitrate. 836 1

In this paper the substrate activities and binding affinities of the stereoisomers of the beta,gamma-bidentate Rh(H2O)4ATP and alpha,beta, gamma-tridentate Rh(H2O)3ATP complexes toward selected members of the kinase family of enzymes are reported. Hexokinase and glycerokinase were found to be specific for the delta beta, gamma-bidentate Rh(H2O)4ATP isomer as substrate while adenylate kinase was found to specifically catalyze the reaction of the delta beta,gamma-bidentate Rh(H2O)4ATP isomer. Pyruvate kinase recognized both the delta beta,gamma-bidentate Rh(H2O)4ATP isomer and the delta beta-P, exo alpha-P alpha,beta,gamma-tridentate Rh(H2O)3ATP isomer as substrates in the catalyzed phosphorylation of the alternate substrate, glycolate. 31P NMR analysis of the respective product complexes showed that alpha-P phosphoryl ligand exchange had not preceded or followed catalysis. Creatine kinase was found to be specific for the delta beta-P, exo alpha-P alpha,beta,gamma-tridentate Rh(H2O)3ATP isomer. Discrimination of the Rh(H2O)nATP isomers via preferential binding of the substrate-active isomer was observed for hexokinase and adenylate kinase but not for glycerokinase, fructose-6 phosphate kinase, creatine kinase, arginine kinase, or acetate kinase.
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PMID:Investigations of kinase substrate specificity with aqua Rh(III) complexes of adenosine 5'-triphosphate. 838 48

The coordination scheme of Mn2+ in the hexokinase-MnIIADP-nitrate-lyxose complex has been determined by electron paramagnetic resonance (EPR) spectroscopy with 17O-enriched ligands. Nitrate binds to the active site of hexokinase when MnIIADP and a sugar substrate or analogue are present. The binding of nitrate enhances inhibition by glucose when ADP is present and narrows the EPR signals of the enzyme-bound MnIIADP complex in the presence of sugar substrates or analogues. Experiments using regiospecifically 17O-enriched ADP, 17O-enriched nitrate, and 17O-enriched water establish the coordination scheme of Mn2+. The EPR experiments show that ADP is a beta-monodentate ligand and that nitrate binds directly to Mn2+. Four water molecules complete the coordination sphere of the enzyme-bound Mn2+. The dissociation constant (Kd approximately 8 mM) of nitrate for the complex with enzyme, MnIIADP, and lyxose was obtained from titration experiments. These results suggest that nitrate-stabilized, dead-end complexes of hexokinase may be useful in stabilizing the closed conformation of this "hinge-bending" enzyme for crystallographic experiments.
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PMID:The structure of the MnIIADP-nitrate-lyxose complex at the active site of hexokinase. 839 83

Osmotic stress is used to measure solvation changes that accompany the conformational changes of an active enzyme. For hexokinase both the equilibrium dissociation constant and the kinetic Michaelis-Menten constant for glucose vary linearly, and to the same extent, with the activity of water in the protein medium, as adjusted with large molecular weight (> 2000) osmolytes. The variation over the whole osmotic pressure range studied indicates that glucose binding is accompanied by the release of at least 65 +/- 10 water molecules, and this is reversed on enzyme turnover. The results indicate that near the physiological range of pressures the number may be higher. Most of this water, which behaves like an inhibitor, likely comes from the cleft which is induced to close around the substrate. Such large dehydration/rehydration reactions during turnover imply a significant contribution of solvation to the energetics of the conformational changes. Osmotic stress is a method of general applicability to probe water's contribution to functioning molecules.
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PMID:Measured change in protein solvation with substrate binding and turnover. 850 33

4-Aminodiphenylamine (N-phenyl-1,4-phenylenediamine, CAS 101-54-2) and its water-soluble HCl salt (CAS 2198-59-6) were demonstrated to be efficient mediators for glucose oxidase, lactate oxidase, xanthine oxidase, and lysine oxidase. Using cyclic voltammetry, single oxidative peak potentials were observed for scans ranging from 0 to 0.5 V vs Ag/AgCl. The half-wave potential for both preparations was 0.11 V vs Ag/AgCl at pH 7 and decreased 59 mV per unit pH increase. Peak current data were analyzed to estimate diffusivities of 0.8 x 10(-5) cm2/s for soluble 4-ADPA HCl, and 2.36 x 10(-5) cm2/s for 4-ADPA solubilized in 2.5 mM 2-hydroxypropyl-beta-cyclodextrin. The overall second-order kinetic constants (k) for the reaction of reduced glucose oxidase with oxidized 4-ADPA HCl and 4-ADPA in cyclodextrin were estimated to be 1.8 x 10(5) and 1.7 x 10(-5) M-1 s-1, respectively, using cyclic voltammetry measurements at varied scan rates and enzyme concentrations. Both preparations proved to be suitable electron acceptors for horseradish peroxidase, as indicated by changes in absorbance spectra upon oxidation or reduction. The electrochemical and spectral behavior of the preparations were applied in conjunction with glucose oxidase to devise mediated amperometric and hydrogen peroxide-coupled spectrophotometric assays for glucose. The results of both assays compared favorably with the hexokinase reference method.
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PMID:Dual functionalities of 4-aminodiphenylamine in enzymatic assay and mediated biosensor construction. 859 91

A case of Iotrolan encephalopathy is reported. A 66-year-old woman, suffering from subarachnoid hemorrhage, was admitted to our department on January 17th, 1995. After an operation for aneurysmal clipping and ventriculo-peritoneal shunt, she was discharged with no neurological deficiency. CT scan revealed ventricular enlargement and slight periventricular lucency. She was re-admitted on January 4th, 1996. She was suffering from nausea, vomiting, right hemiparesis, right hemi-hypesthesia and disturbance of consciousness. CT scan demonstrated right thalamic bleeding and bilateral ventricular hemorrhage. Further ventricular enlargement was also revealed. With medical treatment, her symptoms were relieved gradually. But disorientation and memory disturbance continued. Shuntography with Iotrolan was performed on February 2nd, 1996. The ventriculo-peritoneal shunt was demonstrated to be occluded on the abdominal side. The volume of Iotrolan used was about 8cc. She became very restless on the night of the examination. Her temperature was up to 38. CT on February 4th demonstrated brain penetration of the Iotrolan. Revision of ventriculo-peritoneal shunt, administration of steroids and hydration was performed. CSF findings demonstrated no abnormalities. Her symptoms were relieved gradually. Iotrolan is a non-ionic contrast media of dimer type, composed of C37 H48 I6 N6 O18. Its distinctive features are low distributing coefficient and high affinity with water. Contrasting several reports of Metrizamide encephalopathy, only 2 cases of Iotrolan encephalopathy were reported. Iotrolan is reported to be much safer than Metrizamide. We were able to find brain penetration by Iotrolan. It is expected to be a characteristic radiological finding of encephalopathy induced by contrast media. The mechanism of Iotrolan encephalopathy is obscure. Several theories concerning Metrizamide encephalopathy are proposed. These are (1) inhibition of hexokinase, (2) inhibition of acethylcholinesterase, (3) immunological mechanism and (4) vascular disturbance. Iotrolan has no 2-deoxy-glucose structure. The inhibition theory of hexokinase is least expected. Related matters are circulatory disturbance of liquor, dehydration, excessive contrast media, advanced age, diabetes mellitus, hypertension, epileptic patients and patients taking phenothiazines. Prompt therapy is important. Removal of contrast media, hydration and administration of steroids should be performed as early as possible.
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PMID:[A case of Iotrolan encephalopathy]. 893 76

Three glycolytic enzymes, hexokinase, phosphoglycerate kinase, and pyruvate kinase, were fluorine labeled in the yeast Saccharomyces cerevisiae by biosynthetic incorporation of 5-fluorotryptophan. 19F NMR longitudinal relaxation time measurements on the labeled enzymes were used to assess their rotational mobility in the intact cell. Comparison with the results obtained from relaxation time measurements of the purified enzymes in vitro and from theoretical calculations showed that two of the labeled enzymes, phosphoglycerate kinase and hexokinase, were tumbling in a cytoplasm that had a viscosity approximately twice that of water. There were no detectable signals from pyruvate kinase in vivo, although it could be detected in diluted cell extracts, indicating that there was some degree of motional restriction of the enzyme in the intact cell.
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PMID:19F NMR measurements of the rotational mobility of proteins in vivo. 899 36

The purpose of this study was to test the hypothesis that the rate and extent of glycogen supercompensation in skeletal muscle are increased by endurance exercise training. Rats were trained by using a 5-wk-long swimming program in which the duration of swimming was gradually increased to 6 h/day over 3 wk and then maintained at 6 h/day for an additional 2 wk. Glycogen repletion was measured in trained and untrained rats after a glycogen-depleting bout of exercise. The rats were given a rodent chow diet plus 5% sucrose in their drinking water and libitum during the recovery period. There were remarkable differences in both the rates of glycogen accumulation and the glycogen concentrations attained in the two groups. The concentration of glycogen in epitrochlearis muscle averaged 13.1 +/- 0.9 mg/g wet wt in the untrained group and 31.7 +/- 2.7 mg/g in the trained group (P < 0.001) 24 h after the exercise. This difference could not be explained by a training effect on glycogen synthase. The training induced approximately 50% increases in muscle GLUT-4 glucose transporter protein and in hexokinase activity in epitrochlearis muscles. We conclude that endurance exercise training results in increases in both the rate and magnitude of muscle glycogen supercompensation in rats.
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PMID:Effect of endurance exercise training on muscle glycogen supercompensation in rats. 904 57


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