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)

ATP and citrate, the well known inhibitors of phosphofructokinase (ATP: D-fructose 6-phosphate 1-phosphotransferase, EC 2.7.1.11), were found to inhibit the activities of the multiple forms of phosphoglucomutase (alpha-D-glucose 1,6-bisphosphate: alpha-D-glucose 1-phosphate phosphotransferase, EC 2.7.5.1) from rat muscle and adipose tissue. This inhibition could be reversed by an increase in the glucose 1,6-bisphosphate (Glc-1,6-P2) concentration. Other known activators (deinhibitors) of phosphofructokinase, viz. cyclic AMP, AMP, ADP or Pi, had no direct deinhibitory action on the ATP or citrate inhibited multiple phosphoglucomutases. Cyclic AMP and AMP, could however lead indirectly to deinhibition of the phosphoglucomutases, by activating phosphofructokinase which catalyzes the ATP-dependent phosphorylation of glucose 1-phosphate to form Glc-1,6-P2, the la-ter then released the multiple phosphoglucomutases from ATP or citrate inhibition. The Glc-1,6-P2 was also found to exert a selective inhibitory effect on hexokinase (ATP: D-hexose 6-phosphotransferase, EC 2.7.1.1) type II, the predominant form in skeletal muscle. This selective inhibition by Glc-1,6-P2 was demonstrated on the multiple hexokinases which were resolved by cellogel electrophoresis or isolated by chromatography on DEAE-cellulose. Based on the in vitro studies it is suggested that during periods of highly active epinephrine-induced glycogenolysis in muscle, the Glc-1,6-P2, produced by the cyclic AMP-stimulated reaction of phosphofructokinase with glucose 1-phosphate, will release the phosphoglucomutases from ATP or citrate inhibition, and will depress the activity of muscle type II hexokinase.
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PMID:Complementarity in the regulation of phosphoglucomutase, phosphofructokinase and hexokinase; the role of glucose 1,6-bisphosphate. 12 9

Three glucose-phosphorylating enzymes having different specificities for glucose and fructose were separated from the cell-free extract of Candida tropicalis by means of ammonium sulfate fractionation and chromatography on DEAE-cellulose and Sephadex G-100. Two of them, which phosphorylated fructose 1.5 times faster than glucose, were designated as hexokinase I and II (ATP : D-hexose 6-phosphotransferase, EC 2.7.1.1.), and the other with very low or no fructose-phosphorylating activity, as glucokinase (ATP : D-glucose 6-phosphotransferase, EC 2.7.1.2). Km values for glucose with both hexokinase I and glucokinase were 0.3 mM, and that for fructose with hexokinase I was 2.2 mM. Time-course changes in the levels of these enzymes in C. tropicalis growing on glucose and on n-alkane revealed that hexokinase was induced specifically by the sugars, while glucokinase was a constitutive enzyme. Addition of cycloheximide to the culture medium prevented the increase in the hexose-phosphorylating activity and in the Fru/Glu ratio (the ratio of enzymatic phosphorylation of fructose to that of glucose) in the cells. Although Candida lipolytica also contained hexokinase and glucokinase, both enzymes seemed to be constitutive.
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PMID:Glucose-phosphorylating enzymes of Candida yeasts and their regulation in vivo. 83 48

Human erythrocyte hexokinase (ATP: D-hexose 6-phosphotransferase, EC 2.7.1.1) was inhibited competitively with respect to MgATP2- by glucose-6-P (Ki - 10.8 muM) and fructose-6-P (Ki = 160 muM). Low concentrations of inorganic phosphate were competitive with respect to glucose-6-P and fructose-6-P, although higher concentrations of Pi were not able to overcome completely the inhibition by the hexose phosphates. The results are consistent with a model in which hexokinase exists in equilibrium either as free or phosphate-associated enzyme, the latter having a reduced but still substantial affinity for hexose phosphate. An alternative explanation could be found in the presence of two different enzymes, one with a high affinity for glucose-6-P being sensitive to regulation by Pi, one with a lower affinity for glucose-6-P being insensitive to Pi. A similar but less pronounced effect of Pi, was found on the inhibition by 2,3-diphosphoglycerate (Ki = 4.0 mM). Pi in the absence of inhibitor was also a competitive inhibitor with respect to MgATP2- (Ki = 20 mM). Furthermore a competitive inhibition with respect to MgATP2- was found by fructose 1,6-diphosphate (Ki = 4.3 mM), glycerate-3-P (Ki = 3.8 mM), glycerate-2-P (Ki = 12.5 mM), MgADP- (Ki = 1.0 mM) and MgAMP (Ki = 1.7 mM).
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PMID:Regulation of human erythrocyte hexokinase. The influence of glycolytic intermediates and inorganic phosphate. 91 66

1. Human erythrocyte hexokinase (ADP:D-hexose 6-phosphotransferase, EC 2.7.1.1) was purified 50 000--100 000-fold with a final specific activity of about 25--50 units/mg protein using gel-filtration, ion-exchange chromatography and affinity chromagraphy. 2. After isoelectrofocusing ofthe preparation one major protein band could be detected besides a minor band. THe isoelectric point of the major protein band was found to be 4.7. 3. After purification the enzyme could be stabilized in a medium containing inorganic phosphate, glucose, glycerol and mercaptoethanol. 4. The molecular weight was determined by gel-filtration and was found to be 132 000+/-8000. 5. The enzyme shows a broad pH optimum ranging from 7.0 to 8.4. 6. The kinetic behavior of the purified enzyme at 37 degrees C was somewhat different from the normal Michaelis-Menten kinetics due to its instability. The affinity constants were 0.048--0.080 mM for glucose and 0.57--1.0 mM for Mg-ATP. 7. The enzyme was specific for Mg- ATP as the nucleotide substrate. Mg-UTP, Mg-ITP,Mg-GTP and Mg-CTP were not converted to corresponding diphosphates. Several hexoses could be phosphorylated by the enzyme. Mannose could be phosphorylated at the same rate as glucose, although the affinity for the enzyme was lower (5m=0.60mM). Much lower rates and lower affinities were found with 2-deoxy-D-glucose (5m=1.0mM), D(+)-glucosamine (5m=4.5 mM) and fructose (5m=10 mM). N-acetyl-D-glucosamine , galactose andsorbose were not phosphorylated at all.
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PMID:Purification and some properties of human erythrocyte hexokinase. 95 36

The activities of glucose-6-phosphate dehydrogenase (D-glucose-6-phosphate: NADP oxidoreductase, G6PD), 6-phosphogluconate dehydrogenase (6-phospho-D-gluconate: NADP oxidoreductase, 6PGD), hexokinase (ATP: D-hexose 6-phosphotransferase, Hx), lactate dehydrogenase (D-lactate: NAD oxidoreductase, LDH). glutamate oxaloacetate transaminase (L-aspartate: 2 oxoglutarate aminotransferase, GOT) and dihydrofolate reductase (DHFR) were measured at 8 a.m. in leucocytes of healthy individuals and patients with chronic myeloid leukaemia (CML), chronic lymphatic leukaemia (CLL), myelofibrosis with myeloid metaplasia and polycythaemia vera. In view of the heterogeneity of the leucocyte populations in these conditions, the enzyme activities were correlated to the number of immature cells in CML and to the percentage of lymphocytes in CLL. No differences in the enzyme activities were found between the white cells of healthy individuals, myelofibrosis with myeloid metaplasia and polycythaemia vera. In CML the activities of all enzymes except GOT correlated directly with the number of immature cells; an inverse correlation with the number of lymphocytes was observed in CLL. GOT was the only enzyme whose activity correlated with the number of lymphocytes in the cell suspension. Furthermore, a significantly higher activity of this enzyme was found in Ficoll-isolated CLL lymphocytes as compared to normal lymphocytes.
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PMID:Blood leucocyte enzymes. II. Activities at 8-9 a.m. in cells of normal subjects, chronic lymphatic leukaemia and chronic myeloid leukaemia patients. 105 70

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 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

A panel of monoclonal antibodies against rat brain hexokinase (ATP: D-hexose 6-phosphotransferase, EC 2.7.1.1) has been employed to investigate the orientation of the mitochondrially bound enzyme on the mitochondrial surface. Based on their ability to immunoprecipitate truncated forms of the protein, obtained by in vitro translation of truncated versions of the mRNA, the epitopes for seven monoclonal antibodies were mapped to regions consisting of 20-50 amino acid residues within the sequence of the N-terminal half of the enzyme. There is extensive sequence similarity between the N- and C-terminal halves of this enzyme, which is thought to have evolved by a process of gene duplication and fusion. However, these antibodies react selectively with epitopes in the N-terminal half, and thus epitopic regions for several of these antibodies could be further defined by eliminating from consideration regions showing substantial sequence similarity with the C-terminal half. The epitope for one of the monoclonal antibodies, designated 4D4, was shown to involve the extreme N-terminus of the enzyme; selective proteolytic modification of this region resulted in loss of immunoreactivity. Relative location of epitopes for three other antibodies, designated 2B, 1C5, and 4C5, within a 20-residue segment was deduced from effects of modifying sulfhydryl residues within this segment on immunoreactivity. Thus, by a combination of sequence analysis and experimental methods, the epitopes for these seven antibodies could be localized to defined regions within the overall sequence. The ability of these antibodies to prevent binding of hexokinase to mitochondria, and their ability to recognize the mitochondrially bound enzyme, provided a basis for assessing the relative proximity of the corresponding epitopes to the mitochondrial surface when the enzyme was bound. The disposition of the bound enzyme on the mitochondrial surface was deduced by relating these results to the proposed structure for brain hexokinase.
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PMID:Disposition of mitochondrially bound hexokinase at the membrane surface, deduced from reactivity with monoclonal antibodies recognizing epitopes of defined location. 171 67

Heterogenous stock mice in addition to mice selectively bred to maximally differ in their severity of alcohol withdrawal seizures (withdrawal seizure-resistant (WSR) and withdrawal seizure-prone (WSP] were used to provide evidence in favor of the importance of the rapidly changing distribution of brain hexokinase (ATP: D-hexose 6-phosphotransferase, EC 2.7.1.1) (HK). An ischemic response at 15, 30, 60 and 120 s after killing showed a decreasing cerebellar cytosolic HK concentration of 31%, 15%, 14% and 10% while the cerebral concentrations were 23%, 13%, 13% and 14%, respectively. WSR and WSP mice given an acute i.p. dose of 4 g/kg of alcohol showed opposite HK responses. Cytosolic HK in WSR mice decreased 18.5%, while WSP mice showed an increase of 20.3% over paired saline-injected controls. When ischemia was allowed to proceed in WSP mice following an in vivo alcohol treatment, cytosolic HK decreased in parallel to mice not given alcohol. These data suggest that alcohol can cause an HK redistribution in vivo which could play a role in the differing sensitivities of WSR and WSP mice to alcohol related seizures.
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PMID:Hexokinase redistribution in vivo. 232 57

Porcine hepatic glucokinase (ATP: D-hexose 6-phosphotransferase EC 2.7.1.1) has been purified by a modification of the procedure for its purification from rats. However, difficulties were encountered with endogenous proteases and the reliability of a source for porcine livers. The molecular weight has been determined to be 60,400 +/- 1,400 by sodium dodecyl sulfate, polyacrylamide gel electrophoresis. The enzyme has been characterized kinetically. The parameter values, S0.5 (glucose) and Hill coefficient (nH) are 2.4 mM and 1.9 respectively under sulfhydryl-reducing conditions. The enzyme undergoes the two sulfhydryl-related decays of its activity previously observed in the enzyme isolated from rat (Tippett PS, Neet KE: Arch Biochem Biophys 222:285-298, 1983). The enzyme is inhibited by palmitoyl-CoA, Ki (apparent) = 1.0 microM, nH = 1.8; this concentration of inhibitor is significantly below its critical micelle concentration. Physically and kinetically glucokinase isolated from pig is similar to the enzyme isolated from rat. The porcine system provides a second source for isolation and further characterization of this important and unusual enzyme.
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PMID:The regulatory kinetic properties of porcine hepatic glucokinase. 277 Jul 13


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