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. Measurements were made of the activities of the four key enzymes involved in gluconeogenesis, pyruvate carboxylase (EC 6.4.1.1), phosphoenolpyruvate carboxylase (EC 4.1.1.32), fructose 1,6-diphosphatase (EC 3.1.3.11) and glucose 6-phosphatase (EC 3.1.3.9), of serine dehydratase (EC 4.2.1.13) and of the four enzymes unique to glycolysis, glucokinase (EC 2.7.1.2), hexokinase (EC 2.7.1.1), phosphofructokinase (EC 2.7.1.11) and pyruvate kinase (EC 2.7.1.40), in livers from starved rats perfused with glucose, fructose or lactate. Changes in perfusate concentrations of glucose, fructose, lactate, pyruvate, urea and amino acid were monitored for each perfusion. 2. Addition of 15mm-glucose at the start of perfusion decreased the activity of pyruvate carboxylase. Constant infusion of glucose to maintain the concentration also decreased the activities of phosphoenolpyruvate carboxylase, fructose 1,6-diphosphatase and serine dehydratase. Addition of 2.2mm-glucose initially to give a perfusate sugar concentration similar to the blood sugar concentration of starved animals had no effect on the activities of the enzymes compared with zero-time controls. 3. Addition of 15mm-fructose initially decreased glucokinase activity. Constant infusion of fructose decreased activities of glucokinase, phosphofructokinase, pyruvate carboxylase, phosphoenolpyruvate carboxylase, glucose 6-phosphatase and serine dehydratase. 4. Addition of 7mm-lactate initially elevated the activity of pyruvate carboxylase, as also did constant infusion; maintenance of a perfusate lactate concentration of 18mm induced both pyruvate carboxylase and phosphoenolpyruvate carboxylase activities. 5. Addition of cycloheximide had no effect on the activities of the enzymes after 4h of perfusion at either low or high concentrations of glucose or at high lactate concentration. Cycloheximide also prevented the loss or induction of pyruvate carboxylase and phosphoenolpyruvate carboxylase activities with high substrate concentrations. 6. Significant amounts of glycogen were deposited in all perfusions, except for those containing cycloheximide at the lowest glucose concentration. Lipid was found to increase only in the experiments with high fructose concentrations. 7. Perfusion with either fructose or glucose decreased the rates of ureogenesis; addition of cycloheximide increased urea efflux from the liver.
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PMID:Induction and suppression of the key enzymes of glycolysis and gluconeogenesis in isolated perfused rat liver in response to glucose, fructose and lactate. 435 83

Earlier work from this laboratory has determined that glucose plays an important role in the mechanisms regulating meiotic maturation in mammalian oocytes. In the current study, we have further explored the role of glucose in hormone-induced germinal vesicle breakdown (GVB) in an effort to better understand how glucose utilization and metabolism relate to the control of meiotic maturation in mouse cumulus cell-enclosed oocytes (CEO). When CEO were cultured in medium containing 4 mM hypoxanthine (to maintain meiotic arrest), 5.5 mM glucose, and 0.23 mM pyruvate, follicle-stimulating hormone (FSH) stimulated lactate accumulation in a time-dependent manner. Addition of 2-deoxyglucose (2-DG) to the medium at various times after the initiation of culture resulted in rapid termination of lactate production and suppression of FSH-induced GVB scored after 18 hr of culture, the effectiveness diminishing the longer the delay before addition of 2-DG. By 8 hr, addition of 2-DG was without effect on GVB. Similar effects were seen when FSH-treated CEO were washed free of glucose. In a 2-DG dose-response experiment, gonadotropin-induced lactate production was prevented, but this inhibition did not necessarily prevent GVB. The activities of six metabolic enzymes were measured in extracts of freshly isolated complexes, and in order of increasing activity were: hexokinase, 6-phosphogluconate dehydrogenase, glucose-6-phosphate dehydrogenase, phosphofructokinase, lactate dehydrogenase, and pyruvate kinase. Of the six enzymes examined, only hexokinase activity was increased in CEO exposed to FSH. CEO were cultured in microdrops in the presence or absence of FSH, and aliquots from the same microdrop were assayed for glucose, lactate, and pyruvate. In response to FSH, utilization of glucose in microdrop cultures by CEO was markedly increased and was accompanied by comparable lactate production and limited pyruvate production. Cycloheximide and alpha-amanitin both blocked FSH-induced oocyte maturation, but only cycloheximide prevented the increase in hexokinase activity and glucose consumption. These data suggest that hexokinase is an important rate-limiting enzyme for glucose utilization that is under translational control and participates in the mechanisms controlling the reinitiation of meiosis. However, stimulation of glycolytic activity does not appear to be a necessary concomitant for meiotic induction.
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PMID:Glucose utilization during gonadotropin-induced meiotic maturation in cumulus cell-enclosed mouse oocytes. 872

During adaptation to hypoxic and hyperoxic conditions, the genes involved in glucose metabolism are upregulated. To probe involvement of the transcription factor hypoxia-induced factor-1 (HIF-1) in hexokinase (HK) II expression in human pulmonary cells, A549 cells and small-airway epithelial cells (SAECs) were exposed to stimuli such as hypoxia, deferoxamine (DFO), and metal ions. The largest increase in HK-II (20-fold for mRNA and 2.5-fold for enzymatic activity) was observed in A549 cells when exposed to DFO. All stimuli selectively increased the 5.5-kb rather than 4-kb transcript in A549 cells. Cycloheximide and actinomycin D inhibited these responses. In addition, cells were transfected with luciferase reporter constructs driven by the full-length HK-II 5'-regulatory region (4.0 kb) or various deletions of that region. A549 cells transfected with the 4.0-kb construct and exposed to hypoxia or DFO increased their luciferase activity 7- and 10-fold, respectively, indicating that HK-II induction is, at least in part, due to increased gene transcription. Sixty percent of the inducible activity of the 4.0-kb construct was shown to reside within the proximal 0.5 kb. Additionally, cotransfection with a stable HIF-1 mutant and the 4.0-kb promoter construct resulted in increased luciferase activity under normoxic conditions. These results strongly suggest that HK-II is selectively regulated in pulmonary cells by a HIF-1-dependent mechanism.
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PMID:Hypoxia induces hexokinase II gene expression in human lung cell line A549. 1066 26

The induction of fructosylsucrose-synthesizing activity (FSS) by sugars was tested using detached primary leaf blades of several wheat (Triticum aestivum L.) cultivars, immersed in different sugars solutions for 24 h in the dark. The highest induction was brought about by sucrose, while glucose, fructose and maltose also caused significant induction. 5-Ketofructose, 3-methylglucose and 6-deoxyglucose, which cannot be metabolized by plants, produced no induction at all. The fact that mannose also failed to induce FSS and that mannoheptulose did not inhibit the induction by sucrose suggests that the hexokinase-sensing system may not be involved. The protein phosphatase inhibitor okadaic acid and the calmodulin-dependent protein kinase antagonist W7 inhibited FSS induction while some types of protein kinase inhibitors, such as staurosporine and genistein, had less or no effect, respectively. Cycloheximide and cordycepin completely inhibited the induction response, indicating that transcription and translation are necessary for the FSS induction. Northern blot experiments using a sucrose:fructan-6-fructosyl transferase probe gave a clear indication that the mRNA for this enzyme, which is almost absent in control leaves, is dramatically increased after a 24-h treatment with 500 mM sucrose, and confirmed the inhibition produced by protein kinase and protein phosphatase inhibitors. Our data indicate that protein kinase and protein phosphatase activities take part in the chain of events that intervenes in the induction of fructan synthesis by sugars.
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PMID:Protein kinase and phosphatase activities are involved in fructan synthesis initiation mediated by sugars. 1155 97

High-glucose exposure down-regulates protein kinaseC beta II posttranscriptionally in rat and human vascular smooth muscle cells and contributes to increased cell proliferation. High-glucose-induced mRNA destabilization is specific for PKC beta II mRNA, while PKC beta I and other PKC mRNA are not affected. This study focused on whether glucose metabolism was required. The effect was blocked by cytochalasin B, suggesting a requirement for glucose uptake. Glucosamine did not mimic the effect, indicating that metabolism via hexosamine pathway was not involved. The effect was hexokinase-independent since 3-O-methylglucose, in a dose-dependent manner, mimicked high-glucose effects. Cycloheximide did not block the effect excluding dependency on new protein synthesis. Wortmannin and LY294002, phosphoinositide 3-kinase (PI3-kinase) inhibitors, blocked glucose effects in the presence of 5,6-dichloro-1-beta-d-ribofuranosylbenzimidazole. Glucose and 3-O-methylglucose activated PI3-kinase, and LY294002 blocked glucose effects on Akt phosphorylation. In these cells, high-glucose concentrations activated a metabolically linked signaling pathway independent of glucose metabolism to regulate mRNA processing.
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PMID:Phosphoinositide 3-kinase mediates protein kinase C beta II mRNA destabilization in rat A10 smooth muscle cell cultures exposed to high glucose. 1206 8