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)

Analogues of ATP and UTP bearing C-5'-S-P ester bonds were found not to be substrates but weak competitive inhibitors of Escherichia coli RNA polymerase. The K-i values of the analogues obtained in the transcription of poly[d(A-T)] or poly(dT) under various conditions are in the order of millimolar. Evidence was derived from proton magnetic resonance spectra that nucleotides with C-5'-S-P bonds do not exist in gauche-gauche conformation normally adopted by natural occurring nucleotides. This leads us to assume that the gauche-gauche conformation is an essental prerequisite for substrates of RNA polymerase. Ado-5'-S-PPP substituted for ATP as substrate of hexokinase from yeast rather effectively thus indicating that a distinct stereochemical orientation of the alpha-phosphate ester bond is not a stringent requirement for substrates of this enzyme.
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PMID:Properties of ATP and UTP analogues with P-S-C-5' bonds. 109 46

It is demonstrated that N-bromoacetyl-D-galactosamine acts as a substrate-like reagent for yeast hexokinases A and B, producing affinity labeling. At the order of 10(-3) M reagent concentrations, rapid inactivation of the enzyme is produced: the kinetics are consistent with dependence upon a reversible inhibitor-enzyme initial complex, with a dissociation constant of 3.8 x 10(-3) M for hexokinase B at 35 degrees, pH 8.5. The glucose analog is 30-fold less effective, presumably due to self-protection. The inactivating reaction is an order of magnitude faster than that with bromoacetate. All the alkylation of hexokinase B was shown to occur at two thiol groups per subunit, associated stoichiometrically with inactivation. Unlike the reaction there of simple alkylators, two nonessential thiols per subunit are left unattacked when this inactivation reaction is complete. Protection against the affinity alkylation is exerted by the substrates glucose, mannose, fructose, glucose 6-phosphate, fructose 6-phosphate, ATP-Mg, and ADP-Mg, in proportion to their affinities for the active center. Free ATP also protects. Mg2+ alone has no influence, and Mn2+ gives a slight acceleration, when correction is made for a slow inactivation that occurs when the enzyme is incubated at 35 degrees with Mn2+ alone. Galactose, virtually a nonsubstrate, has no influence on the affinity alkylation, but N-acetylgalactosamine, a nonsubstrate and a weak inhibitor of the enzymic reaction, has an accelerating effect. An interpretation is made in terms of binding to a site that influences the active center. This affinity label should provide a means of isolating a peptide containing active-center-related groups.
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PMID:Essential thiols of yeast hexokinase: alkylation by a substrate-like reagent. 109 53

An attempt was made to gain insight into the mechanism of orthophosphate attenuation of glucose-6-P inhibition of bovine brain hexokinase I (ADP:D-hexose 6-phosphotransferase, EC 2.7.1.1) from experiments of ligand binding and initial rate kinetics. Studies of glucose-6-P and phosphate binding to hexokinase reveal one binding site per hexokinase molecule. A model is presented which is consistent with the binding and kinetic data currently available on the alleviation of glucose-6-P inhibition of brain hexokinase by phosphate. The model implies that hexokinase may exist in equilibrium either as a free or phosphate-associated enzyme. The kinetic parameters of the two enzyme forms are similar except in their ability to bind glucose-6-P. It is suggested that the dissociation constant for glucose-6-P is relatively very high for hexokinase to which phosphate is bound. Phosphate appears to bind at an allosteric site on the enzyme, whereas glucose-6-P is associated either at the active site or at an allosteric site which overlaps the catalytic site.
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PMID:Studies on the mechanism of orthophosphate regulation of bovine brain hexokinase. 111 35

The effects of exercise and of food restriction on Zucker obese and lean rats were studied. Zucker obese rats pair-fed to lean littermates gained more body fat on the same intake indicating greater efficiency of diet utilization. Exercise significantly reduced the fat pad weights and body fat content of obese rats. Serum insulin levels were higher in the obese rats and were not influenced by exercise. Exercise had no effect on adipose cellularity of the obese rats. Liver tissue in vitro lipogenic capacity and lipogenic enzyme activities were significantly elevated in obese rats. Exercise increased liver tissue hexokinase and in vitro lipogenesis in lean rats. Exercise increased pentose phosphate pathway enzymes in adipose tissue from lean rats only. Although exercise reduced fat content significantly, obese rats were still fatter (27.7% fat) than the lean controls (6.4% fat). The protein content of obese rats was significantly increased by exercise, indicating that physical activity is important in the regulation of protein metabolism.
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PMID:Effects of exercise and of food restriction on the development of spontaneous obesity in rats. 112 64

Alkylation of ATP with iodoacetic acid at pH 6.5 yielded 1-carboxymethyl-ATP which, after alkaline rearrangement, gave N-6-carboxymethyl-ATP. Condensation of this analogue with 1,6-diaminohexane in the presence of a water-soluble carbodiimide generated N-6-[(6-aminohexyl)carbamoylmethyl]-ATP in an overall yield of 40% based on the parent nucleotide ATP. The coenzymic activities of both N-6-adenine-substituted derivatives of ATP were tested with three kinases. Both derivatives showed coenzymic function against hexokinase with the "long" derivative having highest activity (95%) relative to unsubstituted ATP. Their activities towards the other two kinases tested was negligible except with the "long" analogue against glycerokinase (20%). The latter ATP analogue, when bound to Sepharose through its terminal amino group, could be dephosphorylated to the corresponding ADP analogue with soluble hexokinase yielding glucose 6-phosphate in an enzymic "solidphase" fashion. The Sepharose-bound ADP formed could subsequently be phosphorylated back to ATP using soluble acetate kinase. Sepharose-ATP preparations were also used in preliminary affinity chromatography studies using citrate synthase. Alkylation of ADP following the above procedure yielded the corresponding ADP analogue, N-6-[(6-aminohexyl)carbamoylmethyl]-ADP in an overall yield of 40%. Alkylation of AMP yielded the corresponding N-6-[(6-aminohexyl)carbamoylmethyl]-AMP in an overall yield of 45%.
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PMID:Preparation of analogues of ATP, ADP and AMP suitable for binding to matrices and the enzymic interconversion of ATP and ADP in solid phase. 114 Jan 97

D-Glucosamine was found to be phosphorylated by a rat liver extract in the presence of a high concentration of glucose, which was formerly believed to be a strong competitive inhibitor of this reaction. Results suggested that glucosamine may be phosphorylated by high Km hexokinase, i.e. glucokinase [EC 2.7.1.2]. The enzyme involved was separated from specific N-acetyl-D-glucosamine kinase [EC 2.7.1.59]. The phosphorylation was not inhibited by a physiological level of glucose or glucose 6-phosphate, which strongly inhibited low Km hexokinase. The apparent Km of glucokinase for glucosamine was estimated as 8 mM, which is ten times that of low Km hexokinase.
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PMID:Phosphorylation of D-glucosamine by rat liver glucokinase. 115 56

The mitochondrial-bound hexokinases (adenosine triphosphate:D-hexose 6-phosphotransferase) of mammary adenocarcinoma and of normal gland were compared in lactating C3H mice. Treatment of mitochondria isolated from both the normal and neoplastic tissue with 0.5 m NaCl or 0.1 mM glucose 0-phosphate effected the release of about 50% of the bound hexokinase. In the presence of magnesium ion, enzyme from either source attached to mitochondria from either tissue and in all combinations to the same extent. Identification of the isoenzyme complement in the mitochondrial extract by diethylaminoethylcellulose chromatography revealed only types I and II. In the tumor, the hexokinase activity in both the cytosol and the fraction solubilized from mitochondria was predominantly in the form of type I ( 60%). In contrast, the activity released from mitochondria isolated from normal gland was predominately type II, while the cytosol contained almost equivalent amounts of types I and II. While this difference does not explain differences in glucose utilization between the normal and neoplastic tissue, it may provide a means of distinguishing between the two.
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PMID:Identity, release, and binding of mitochondrial-bound hexokinases in mammary glands and adenocarcinomas of lactating mice. 116 11

Heart hexokinase monomer has a molecular weight of 97000 and so20,w 5.2 S. It exists in equilibrium with dimer of 194000 molecular weight and so20,w 8.1 S. The proportions of monomer and dimer presence of added ligands are 91% and 9% respectively. The existence of these forms may be demonstrated by separation on electrophoresis or chromatography. In the presence of the regulatory molecule glucose 6-phosphate, the dimer form of the enzyme is favoured. The glucose 6-phosphate mediated dimerisation is abolished in the presence of phosphate or ATP-Mg and less effectively by free ATP. Glucose has no effect on the manomer-dimer equilibrium. On prolonged storage of hexokinase in glucose 6-phosphate polymers are also formed and polymerisation is further enhanced by removal of the ligand.
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PMID:Heart hexokinase: quaternary structure changes accompanying the binding of regulatory molecules. 118 36

The effect of adenylic acid, glucose-6-phosphate, fructose-1,6-diphosphate and phosphoenolpyruvate on creatine kinase isoenzymes (brain extract, muscle and heart extracts and purified muscle enzyme) was studied. These effectors, especially phosphoenolpyruvate, are shown to inhibit in different degree the reaction of ATP formation catalysed by creatine kinase from all tissues. The effectors do not inhibit the creatine phosphate synthesis in extracts, but depress purified creatine kinase. The interrelationship of the creatine kinase system and the key glycolytic enzymes (phosphofructokinase, hexokinase, pyruvate kinase) is discussed.
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PMID:[The effect of sugar phosphates, phosphoenolpyruvate and adenylic acid on muscle, brain and heart creatine kinases]. 121 66

In the subcommissural organ (SCO) of the guinea pig, rat, golden hamster, and mouse the activity and distribution of enzymes related to the energy-supplying metabolism and of some marker enzymes of different cell organelles have been investigated by means of mostly modified histochemical methods. The results were compared with findings in the ciliated ependyma of the ventricular wall and with those in the ependyma of the choroid plexus of the third ventricle. In the ependymal part of the SCO only a moderate activity of hexokinase is observed in its specialized columnar cells whereas a high activity is present both in the ciliated ependyma and the choroid plexus. - The staining pattern of glucose-6-phosphatase is similar to that of hexokinase but this enzyme is found is the SCO only. - Likewise hexokinase, glycogen granules and enzymes related to glycogen metabolism (phosphoglucomutase, uridine-diphosphoglucose pyrophosphorylase, glycogen synthetase and phosphorylase) are regularly found most numerous and active in the nuclear and supra-nuclear area of the ependymal part. These enzymes are less active in both the other ependymal regions. - Uridine-diphosphoglucose dehydrogenase could not be demonstrated in the SCO. The NADP-linked enzymes of the pentose phosphate shunt, glucose-6-phosphate and 6-phosphogluconate dehydrogenase, show a moderate activity which decreases also from the nuclear towards the apical area of the ependymal cells of the SCO. Enzymes of the glycolytic pathway, such as glucosephosphate isomerase, fructose-6-phosphate kinase, fructose-I,6-diphosphate aldolase, glyceraldehyde-3-phosphate and lactate dehydrogenase, are highly active in the SCO and are located mainly in the supranuclear area, too. Fructose-1,6-diphosphatase could not be demonstrated thus indicating that in the SCO the pathway is most probably only glycolytic but not gluconeogenetic. Compared to the ependyma of the ventricular wall and of the choroid plexus, in the SCO the M type subunits of lactate dehydrogenase predominate. Glycolytic enzymes are also very active in the choroid plexus but less in the ciliated ependyma. Compared to the ciliated ependyma and especially to the ependyma of the choroid plexus, the activities of enzymes which are only present in mitochondria (NAD-linked isocitrate dehydrogenase, succinate dehydrogenase, NAD-linked malate dehydrogenase after preextraction, cytochrome oxidase, 3-hydroxybutyrate and glycerolphosphate and glutamate dehydrogenase) are relatively low. Mitochondria are accumulated near the superior pole of the nuclei as well as in the most apical part of the ependymal cells. - The staining pattern of NADP-linked isocitrate and malate dehydrogenase as well as of NADH dehydrogenase suggests that these enzymes are localized both in and out of mitochondria. The extramitochondrial activity of the first two enzymes might be localized in the cytosol. The extramitochondrial activity of NADH dehydrogenase might be localized in the endoplasmic reticulum...
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PMID:Enzymatic organization of the subcommissural organ. 123 49


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