Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.1.1 (hexokinase)
 5,274 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Photodamage to lens hexokinase has been investigated by exposing the lenses of rat, rabbit and calf eyes to 300 nm irradiation. Hexokinase activity was diminished by 15.9% +/- 5.4 and 23.4% +/- 5.0 upon irradiation of the isolated rat lens for 1 and 2 hours respectively. Irradiation of the whole eye for 2 hours resulted in hexokinase deactivation of 13.6% +/- 5.8 and 19.2% +/- 6.2 for rat and rabbit lens homogenates and 55% +/- 7 for calf lens capsule plus epithelium. Enzyme deactivation was prevented when the isolated lens was irradiated with the vitreous attached. Glucose, catalase or ascorbate added to the medium prior to irradiation, each had a protective effect on hexokinase deactivation. The results are consistent with a mechanism in which photochemical generation of active species of oxygen, via the photosensitizing action of tryptophan photoproducts, plays a significant role in enzyme deactivation.
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PMID:Lens hexokinase deactivation by near-UV irradiation. 335 12

P/2e- stoichiometries in six assay systems spanning different portions of the respiratory chain were estimated by direct determinations of Pi uptake in suspensions of bovine heart mitochondria containing a hexokinase trap. The electron donors were malate + pyruvate, succinate, and ascorbate + N,N,N',N'-tetramethyl-p-phenylenediamine, and the electron acceptors were ferricyanide (Site 1, Site 2, and Sites 1 + 2) and O2 (Sites 1 + 2 + 3, Sites 2 + 3, and Site 3). A major objective was to find conditions in which the six systems yield results in sufficiently good agreement to allow confidence as to their reliability. This objective was achieved, and maximum values of 1.1, 0.5, and 1.0 were observed in the Sites 1, 2, and 3 systems, respectively. This required that the energy-conserving reactions be relatively nonlimiting and that the P/2e- ratios be estimated from the slopes of plots of respiration rate versus phosphorylation rate obtained by inhibiting oxidative phosphorylation with respiratory chain inhibitors. The latter requirement allows avoidance of the effect of an apparent endogenous uncoupler and is based on the observation (Tsou, C. S., and Van Dam, K. (1969) Biochim. Biophys. Acta 172, 174-176) that uncoupling agents at low concentrations decrease the rate of phosphorylation nearly as much in absolute amount at low rates of respiration as at high rates. The maximum P/2e- stoichiometry at Site 1 is considered to be 1.0, and the value observed in the Site 1 system is suggested to be higher as a result of H+ ejection at the transhydrogenase level. Respiratory control due to carboxyatractyloside inhibition was examined and found to differ greatly among the systems. It is pointed out that this observation is not consistent with the lack of complete control being due primarily to ion cycling and that, in view of this, the relatively meager control at Site 3 is not consistent with O2 being reduced on the matrix side of the coupling membrane.
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PMID:Determination of the P/2e- stoichiometries at the individual coupling sites in mitochondrial oxidative phosphorylation. Evidence for maximum values of 1.0, 0.5, and 1.0 at sites 1, 2, and 3. 361 Oct 76

Exposure of rabbit reticulocytes to Fe(II)/ascorbate induced a pronounced decay in hexokinase activity. In reticulocytes, this enzyme is present in at least three different molecular forms, Ia, Ia* and Ib, sub-types of hexokinase type I, which show different intracellular distribution. Hexokinase Ia and Ib are soluble, whereas hexokinase Ia* is almost entirely bound to the mitochondria. Anion exchange chromatography of hexokinase from intact reticulocytes exposed to Fe(II)/ascorbate revealed a selective inactivation of forms Ia and Ib, whereas the form Ia* did not show any decay. Binding to the mitochondrial membrane seems to be responsible for the observed resistance of the form Ia* to the inactivation elicited by Fe(II)/ascorbate. Indeed, by using a cell-free system in which hexokinase Ia* was solubilized using Triton X-100, the decay in hexokinase activity induced by iron/ascorbate involved all three enzymatic forms.
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PMID:Mitochondria-bound hexokinase from rabbit reticulocytes is resistant to the inactivation induced by Fe(II)/ascorbate. 754 32

Rabbit red blood cell hexokinase (EC 2.7.1.1) has been shown to be inactivated in vitro by incubating intact erythrocytes in the presence of an oxygen-radical-generating system represented by ascorbate and iron. It was interesting to note that among the glycolytic enzymes, only hexokinase was found to be susceptible to the action of oxygen radicals, suggesting that the loss of activity of this enzyme may be one of the first signals of cellular damage in rabbit red blood cells. This statement is supported by the fact that, under the experimental conditions used, we did not observe any significant plasma membrane lipid peroxidation nor intracellular proteolysis. Furthermore, mature erythrocytes are unable to synthesize hexokinase as well as other proteins de novo; therefore, the inactivation of this enzyme, which is both the first and one of the rate-limiting enzymes of the glycolytic pathway, could play an important role in determining metabolic impairment of red blood cells, with possible physiological implications. We also investigated the effect of various radical scavengers and antioxidants (glucose, vitamin E, dithiothreitol, flavonoids) which are able to influence the inactivation of hexokinase activity to different extents. Finally, under the experimental conditions used (90 min of incubation at 37 degrees C), we did not observe any difference in the hemolysis of rabbit red blood cells incubated in the presence or absence of ascorbate and iron (hemolysis was about 1% after 90 min of incubation), suggesting that the system used was able to furnish information about the cellular damage produced by oxygen radicals without provoking cell lysis.
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PMID:Inactivation of rabbit red blood cell hexokinase activity promoted in vitro by an oxygen-radical-generating system. 818 13

In this study we investigated the species involved in the process of hexokinase inactivation induced by ascorbic acid/Fe(II) in rabbit erythrocytes. Our results suggest a model in which divalent iron is first oxidized to the trivalent state and then triggers the oxidation of ascorbic acid. The H202 formed during this process accelerates the formation of dehydroascorbic acid, which appears to be necessary and sufficient to induce hexokinase inactivation. This model was validated by showing that: (a) H202-decomposing enzymes, unlike scavengers of the hydroxyl radicals, reduced the extent of hexokinase inactivation; (b) when H202 was used instead of ascorbate/Fe(II), it was unable, even at very high concentrations, to inhibit hexokinase activity; (c) replacing Fe(II) with either Fe(III) or H202 resulted in comparable levels of ascorbic acid-induced hexokinase inactivation; (d) expression of maximal hexokinase inhibiting activity was also triggered via enzyme-catalyzed oxidation of ascorbic acid or direct addition of dehydroascorbic acid; (e) the level of dehydroascorbic acid, which was actively generated in the external medium upon addition of ascorbic acid/Fe(II), increased as a function of time. Taken together, these results demonstrate that the process of hexokinase inactivation induced by ascorbic acid/Fe(II) is mediated by dehydroascorbate and that iron and H202 have the sole function of accelerating its formation.
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PMID:Role of dehydroascorbate in rabbit erythrocyte hexokinase inactivation induced by ascorbic acid/Fe(II). 890 Apr 11

The aim of this study was to investigate the effects of 50 Hz magnetic fields (0.2-0.5 mT) on rabbit red blood cells (RBCs) that were exposed simultaneously to the action of an oxygen radical-generating system, Fe(II)/ascorbate. Previous data obtained in our laboratory showed at the exposure of rabbit erythrocytes or reticulocytes to Fe(II)/ascorbate hexokinase inactivation, whereas the other glycolytic enzymes do not show any decay. We also observed depletion of reduced glutathione (GSH) content with a concomitant intracellular and extracellular increase in oxidized glutathione (GSSG) and a decrease in energy charge. In this work we investigated whether 50 Hz magnetic fields could influence the intracellular impairments that occur when erythrocytes or reticulocytes are exposed to this oxidant system, namely, inactivation of hexokinase activity, GSH depletion, a change in energy charge, and hemoglobin oxidation. The results obtained indicate the a 0.5 mT magnetic field had no effect on intact RBCs, whereas it increased the damage with Fe(II)/ascorbate to a 0.5 mT magnetic field induced a significant further decay in hexokinase activity (about 20%) as well as a twofold increase in methemoglobin production compared with RBCs that were exposed to the oxidant system alone. Although further studies will be needed to determine the physiological implications of these data, the results reported in this study demonstrate that the effects of the magnetic fields investigated are able to potentiate the cellular damage induced in vitro by oxidizing agents.
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PMID:In vitro effects of 50 Hz magnetic fields on oxidatively damaged rabbit red blood cells. 908 63

Hexokinase (E.C. 2.7.1.1), the enzyme responsible for glucose phosphorylation to G-6P, is inactivated by SH reagents and oxyradicals, and its inhibition has been involved in heavy metal toxicity in mammalian systems. In this work, the possibility that hexokinase activity could be affected by both heavy metal binding and oxidative stress conditions also in mussel tissues (Mytilus galloprovincialis Lam.) was investigated. The results obtained in vitro demonstrate that heavy metals inhibited digestive gland hexokinase (with Cd2+ > Cu2+ > Hg2+ > Zn2+ > Pb2+) and suggest a role for GSH in the protection against the heavy metal effects. Hexokinase activity was also reduced by addition of iron/ascorbate, indicating a susceptibility of the enzyme to metal-mediated oxyradical production. The effects of Cu2+ treatment (3 days, 40 micrograms l-1 per animal) on hexokinase activity and on the GSH/GSSG status were then evaluated in mussels exposed to a cycle of air exposure/reimmersion. In Cu-exposed mussels, a significant decrease in hexokinase activity and a parallel reduction in tissue GSH levels were observed, suggesting that the two effects of metal treatment could be related; however, hexokinase activity progressively recovered during air exposure and reimmersion, whereas the level of GSH showed a further decrease during air exposure followed by recovery after reimmersion. The in vitro results therefore indicate that mussel digestive gland hexokinase is susceptible to inactivation by heavy metal binding and suggest a role for GSH in the protection against the effects of heavy metals. The effects of copper were confirmed by the results obtained in vivo. The possible relationship between hexokinase activity and the level of GSH in the digestive gland of control and Cu-exposed mussels during air exposure and reimmersion are discussed, taking into account the balance between pro-oxidant and antioxidant processes at different stages of exposure.
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PMID:In vitro and in vivo effects of heavy metals on mussel digestive gland hexokinase activity: the role of glutathione. 982 40

The oxidized form of vitamin C (dehydroascorbic acid, DHA) completely and irreversibly inactivates recombinant human hexokinase type I, in a pseudo-first order fashion. The inactivation reaction occurs without saturation, indicating that DHA does not form a reversible complex with hexokinase. Further characterization of this response revealed that the inactivation does not require oxygen and that dithiothreitol, while able to prevent the DHA-mediated loss of enzyme activity, failed to restore the activity of the DHA-inhibited enzyme. Inactivation was not associated with cleavage of the peptide chain or cross-linking. The decay in enzymatic activity was however both dependent on deprotonation of a residue with an alkaline pKa and associated with covalent binding of DHA to the protein. In addition, inactivation of hexokinase decreased or increased, respectively, in the presence of the substrates glucose or MgATP. Finally, amino acid analysis of the DHA-modified hexokinase revealed a decrease of cysteine residues. Taken together, the above results are consistent with the possibility that covalent binding of the reagent with a thiol group of cysteine is a critical event for the DHA-mediated loss of hexokinase activity.
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PMID:Dehydroascorbic acid irreversibly inhibits hexokinase activity. 1094 12

Using isolated bovine brain microvessels as an in vitro model of the blood-brain barrier (BBB) we have evaluated the role of free radical generating solutions on some amino acid transport systems operating on the endothelial cell membrane. Fe(2+)/ascorbate, phenylhydrazine and CuSO(4) did not affect any of the transport system tested, while exposure of bovine brain microvessels to tert-butylhydroperoxide (t-BHP) caused a reduced capacity to take up small neutral amino acids via the Na(+)-dependent A-system. The presence of glucose during t-BHP treatment did not prevent this inhibition, which was partially counteracted when the isolated microvessels were incubated with 5mM inosine before the oxidative stress. Incubation of the isolated capillaries with 5mM dithiothreitol, after exposure to t-BHP, resulted in a 50% recovery of the alpha-methylaminoisobutyrate (MeAIB) uptake by the A-system. Treatment with t-BHP, which had no effect on the L-system of neutral amino acid transport, caused a significant decrease of the intracellular levels of ATP, of glutathione (GSH), and of gamma-glutamyltranspeptidase (GGT) activity, while no significant modification of hexokinase (HK) or of alkaline phosphatase (ALKP) activities were observed. Oxidative damage of the BBB appears therefore to impair essentially the metabolic pathways which ensure the energy requirement for the endothelial cells, thus inhibiting the energy-dependent amino acid transport system "A".
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PMID:Effects of different oxidizing agents on neutral amino acid transport systems in isolated bovine brain microvessels. 1191 69

The present study was carried out to assess the influence of sesame oil on blood glucose, lipid peroxidation, and status of antioxidants in normal and streptozotocin (STZ) diabetic rats. Diabetes was induced in adult female albino Wistar rats weighing 180-200 g by administration of STZ (40 mg/kg of body weight) intraperitonially. Both normal and diabetic rats were fed with a commercial diet containing 2% oil supplemented with 6% sesame oil for 42 days. Diabetic rats had elevated levels of blood glucose (322.61 +/- 9.49 mg/dL), glycosylated hemoglobin, vitamin E, thiobarbituric acid-reactive substances (TBARS), and lipid hydroperoxides and decreased levels of hemoglobin, vitamin C, and reduced glutathione (GSH). An increase in glucose-6-phosphatase and fructose-1,6-bisphosphatase activities and a decrease in hexokinase activity were observed in liver and kidney tissues. When diabetic rats fed with sesame oil were compared with diabetic rats, a significant reduction in levels of blood glucose (222.02 +/- 8.27 mg/dL), glycosylated hemoglobin, TBARS, and lipid hydroperoxides and glucose-6-phosphatase and fructose-1,6-bisphosphatase activities and an elevation in hemoglobin, vitamin E, and GSH levels and hexokinase activity were observed. Thus, sesame oil consumption influences beneficially the blood glucose, glycosylated hemoglobin, lipid peroxidation, and antioxidant levels in diabetic rats.
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PMID:Influence of sesame oil on blood glucose, lipid peroxidation, and antioxidant status in streptozotocin diabetic rats. 1617 50


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