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)

(1) The mitochondrial ATPase (EC 3.6.1.3) Ehrlich ascites cell mitochondria, was inhibited by D-glucose under physiological concentrations of ATP. The generation of ADP by the mitochondrial bound hexokinase, seems to be the reason for the D-glucose inhibitory effect. Reversal of the inhibitory effect of ADP on Ehrlich ascites cell mitochondria ATPase by an ATP-regenerating system was achieved. (2) Dissociation of mitochondrial bound hexokinase from the mitochondria eliminated the inhibitory effect of D-glucose. Rebinding of the hexokinase to the mitochondria regenerated the D-glucose inhibitory effect on Ehrlich ascites cell mitochondria ATPase. (3) Bioflavonoids such as quercetin inhibit the mitochondrial hexokinase activity, but do not change the mitochondrial ATPase activity of isolated Ehrlich ascites tumor cell mitochondria. (4) The inhibitory effect of bioflavonoids on mitochondrial bound hexokinase activity is shown to be dissociable from the ascites tumor cell mitochondria and seems to be associated with regulatory rather than catalitic sites of the enzyme.
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PMID:Bioflavonoid regulation of ATPase and hexokinase activity in Ehrlich ascites cell mitochondria. 1 95

Solubilization of bound to outer mitochondrial membrane hexokinase isoenzyme II by glucose-6-phosphate (G-6-P) has been studied. Dissociation of the enzyme-membrane complex was analyzed in both active (in the presence of reaction substrates) and inactive states. The magnitude of the complex dissociation constants was determined under G-6-P action in the presence and absence Mg.ATP. Besides, some kinetic parameters of hexokinase isoenzyme II in its free and bound forms were estimated. It is suggested that the mechanism of dissociation of the hexokinase-membrane complex by G-6-P is coupled with the kinetic mechanism of the reaction catalyzed by hexokinase isoenzyme II.
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PMID:[Solubilization of mitochondria-bound rat skeletal muscle hexokinase isoenzyme II by glucose-6-phosphate]. 818 Feb 76

Fusion constructs incorporating structural elements from mammalian isozymes of hexokinase, Types I-IV, in frame with sequence encoding the green fluorescent protein (GFP) have been made and expressed in hexokinase-deficient M + R 42 cells. Fusion proteins incorporating catalytically active regions from the Type II isozyme, or the entire Type IV sequence, were expressed in catalytically active form. The intracellular localization of the fusion proteins was determined using confocal microscopy. Fusion proteins including the N-terminal halves of the Type I or Type II isozymes were targeted to mitochondria, while the N-terminal half of the Type III isozyme did not confer mitochondrial targeting. The mitochondrial targeting signal was represented by the hydrophobic sequence at the extreme N-termini ("binding domain") of the Type I and Type II isozymes. Inclusion of the binding domain from the Type I isozyme was sufficient to confer mitochondrial binding on GFP itself as well as on constructs including the N-terminal half of Type III hexokinase. However, the Type I hexokinase binding domain was not sufficient to cause mitochondrial targeting of a construct containing the Type IV sequence. These results suggest that, although the binding domain is critical for mitochondrial targeting, other interactions involving an adjacent structure might also play a role. Fusion proteins including the N-terminal half of Type I hexokinase became dissociated from mitochondria under conditions favorable for accumulation of intracellular Glc-6-P. The 2-deoxy analog was much less effective than Glc in causing mitochondrial dissociation of the fusion construct, in accord with previous studies showing 2-deoxy-Glc-6-P to be much less effective than Glc-6-P at promoting release of Type I hexokinase from mitochondria. Dissociation, induced by formation of Glc-6-P or 2-deoxy-Glc-6-P, did not occur with the fusion protein including only the binding domain of Type I hexokinase. This is consistent with previous studies indicating that Glc-6-P-dependent dissociation results from binding of this ligand to a site in the N-terminal half of the enzyme, but which is not likely to be present in the small segment represented by the binding domain. These studies demonstrate the usefulness of this approach in defining structural elements involved in targeting hexokinase isozymes to specific subcellular locations and modulation of that intracellular location by perturbations of metabolic status.
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PMID:Structural determinants for the intracellular localization of the isozymes of mammalian hexokinase: intracellular localization of fusion constructs incorporating structural elements from the hexokinase isozymes and the green fluorescent protein. 928 18

Viruses have developed various strategies to protect infected cells from apoptosis. HIV-1 infected macrophages are long-lived and considered reservoirs for HIV-1. One significant deciding factor between cell survival and cell death is glucose metabolism. We hypothesized that HIV-1 protects infected macrophages from apoptosis in part by modulating the host glycolytic pathway specifically by regulating hexokinase-1 (HK-1) an enzyme that converts glucose to glucose-6-phosphate. Therefore, we analyzed the regulation of HK-1 in HIV-1 infected PBMCs, and in a chronically HIV-1 infected monocyte-like cell line, U1. Our results demonstrate that HIV-1 induces a robust increase in HK-1 expression. Surprisingly, hexokinase enzymatic activity was significantly inhibited in HIV-1 infected PBMCs and in PMA differentiated U1 cells. Interestingly, we observed increased levels of mitochondria-bound HK-1 in PMA induced U1 cells and in the HIV-1 accessory protein, viral protein R (Vpr) transduced U937 cell derived macrophages. Dissociation of HK-1 from mitochondria in U1 cells using a pharmacological agent, clotrimazole (CTZ) induced mitochondrial membrane depolarization and caspase-3/7 mediated apoptosis. Dissociation of HK-1 from mitochondria in Vpr transduced U937 also activated caspase-3/7 activity. These observations indicate that HK-1 plays a non-metabolic role in HIV-1 infected macrophages by binding to mitochondria thereby maintaining mitochondrial integrity. These results suggest that targeting the interaction of HK-1 with the mitochondria to induce apoptosis in persistently infected macrophages may prove beneficial in purging the macrophage HIV reservoir.
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PMID:Role of hexokinase-1 in the survival of HIV-1-infected macrophages. 2560 55