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)

Chick embryo hepatocytes were maintained in monolayer culture in a serum-free chemically defined medium for periods of up to 2 days. Over this time period, insulin provoked selective increases (up to 5-fold) in factors relevant to the control of glycolysis: the activities of phosphofructokinase-1 (PFK-1), phosphofructokinase-2 (PFK-2) and hexokinase isoenzymes and the content of fructose 2,6-bisphosphate (F26BP). Half-maximal effects of insulin on pFK-1 activity were in the physiological range (0.1 nM). Changes in enzyme activities and F26BP content in response to insulin were correlated with stimulation of glycolytic flux as estimated by radioisotopic flux. These data are discussed in relation to known changes which occur in hepatic glycolytic activity and PFK-1 activity in the intact chick around hatching. The effects of insulin on F26BP content, PFK-1 activity and glycolytic flux were mimicked by epidermal growth factor (EGF). In contrast, phorbol esters produced minimal actions on any of the above parameters. Our data indicate that protein kinase C is not involved in the actions of insulin or EGF in control of F26BP content or PFK-1 activity. This work indicates that the related tyrosyl kinase receptors of insulin and EGF may provoke identical responses within hepatocytes, but through the utilization of different transduction systems which merge to common control points.
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PMID:Control of glycolysis in cultured chick embryo hepatocytes. Fructose 2,6-bisphosphate content and phosphofructokinase-1 activity are stimulated by insulin and epidermal growth factor. 214 94

Transient ATP synthesized by preparations enriched with plasmatic membranes of particles from the human placenta in the presence of insulin (4 micrograms/ml) and epidermal growth factor (1 microgram/ml) within 1 min after the addition of hormones at 30 degrees C, was isolated by means of chromatography on Dowex 1 X 8. ATP was synthesized in a medium containing Tris-HCl buffer, pH 7.5, ADP, Mg2+, and Pi during NADH-dependent oxidation in the presence of cytochrome C and oxygen. The amount of ATP was 10(-9) mole/mg protein/min. Quantitative assessment of ATP in lyophilized product was carried out by means of fluorimetry (excitation wavelength--360 nm; emission wavelength--460 nm) of NADH formed during coupled enzymatic reactions involving hexokinase and glucose-6-phosphate dehydrogenase. A possible biological role of peptide growth factor-stimulated formation of transient ATP in plasmatic membranes is discussed.
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PMID:[ATP generation by the plasma membranes of human placental cells as affected by insulin and epidermal growth factor]. 354 74

In order to study the effect of insulin and epidermal growth factor (EGF) on glycolysis in quiescent 3T3 fibroblasts and their mechanisms of action, lactic acid produced by cells and activities of key glycolytic enzymes in cell extracts were determined. Insulin increased lactic acid production; the maximal stimulation occurred at the concentrations above 250 ng/ml and the half-maximal dose was 50 ng/ml. This effect of insulin appeared as early as one hour, and lactic acid production in the presence of insulin linearly increased up to 4 h. The 24-h pretreatment with insulin exhibited no significant effect on the production by cells afterward incubated either with or without insulin. Lactic acid production decreased as the concentration of phloridzin increased. However, insulin stimulation of the production still remained in the presence of phloridzin. Parahydroxymercuribenzoate reduced production only by the equivalent of the increase due to insulin. EGF also increased lactic acid production; this effect occurred at 1 ng/ml and was maximal at 100 ng/ml. The activities of hexokinase, phosphofructokinase and pyruvate kinase in quiescent cells were not increased by insulin, and the affinities for substrates of these enzymes remained unaltered. These findings suggest that glucose uptake is a rate-limiting step in glycolysis in quiescent 3T3 fibroblasts and that the stimulatory effect of insulin on glycolysis is mediated by enhanced glucose entry.
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PMID:Insulin and epidermal growth factor stimulate glycolysis in quiescent 3T3 fibroblasts with no changes in key glycolytic enzyme activities. 623 8

Adult rat hepatocytes aggregated to form floating multicellular spheroids when cultured in Primaria dishes, which have a positively charged surface, in serum-free Williams' medium E (WE) supplemented with insulin and epidermal growth factor (EGF). These hormones were essential for maintenance of the spheroids, whereas the size of the spheroids depended on the inoculum cell density. The spheroids retained in vivo levels of expressions of albumin and glucokinase and synthesized scarcely any DNA even in the presence of insulin and EGF. On transfer to type I collagen-coated dishes, the spheroids gradually disaggregated and the cells formed monolayers, in which the expressions of albumin and glucokinase were suppressed and DNA synthesis and hexokinase activity were increased. DNA synthesis of hepatocytes in monolayer culture was maximal 24 hr after transfer of the spheroids, approximately 80% of the hepatocyte nuclei were labelled with bromodeoxyuridine during culture for 48 hr, and the mitotic index was approximately 70% after 60 hr. These results suggest that, in spheroids, hepatocytes remained in the G0 phase, but that when they formed monolayers, they progressed to the G1 phase and proceeded through the cell cycle in the presence of insulin and EGF. This work shows that the cell cycle of hepatocytes in culture can be manipulated by providing conditions for quiescence as spheroids or growth as monolayers and that the shape of hepatocytes is important for regulating their growth and liver-specific functions.
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PMID:Importance of cell aggregation for expression of liver functions and regeneration demonstrated with primary cultured hepatocytes. 836 Feb 58

A clearer understanding of biochemical properties of oocytes and embryos and their changes in oocyte maturation and embryonic development may have significant clinical implications, especially for in vitro fertilization techniques. Microtechniques and highly sensitive methods such as enzymatic cycling, micro-Western analysis, reverse transcription polymerase chain reaction and so on were employed to study these processes. Low hexokinase activity and high activities of enzymes in the phosphate pathway were characteristic of immature oocytes. During maturation, the activities of hexokinase and phosphofructokinase increased significantly. These changes were used to analyze involvement of epidermal growth factor (EGF) and prostaglandins (PG) in oocyte maturation. EGF is shown to stimulate maturation by increasing PG production in granulosa cells. Electrophysiologically, the sensitivity of oocyte to inositol triphosphate increased and Ca2+ release system developed during maturation. Progesterone production of oocyte and embryos are shown by enzymatic cycling and other methods using radiometry. This hormone produced by embryos themselves may play a role in embryonic development in intracrine fasion. There is 100-fold increase in glucose uptake from oocyte to blastocyst in mice. A switch in substrate preference of the embryo from pyruvate to glucose during preimplantation development may be explained by increases in the activity of hexokinase and expression of glucose transporter, GLUT1. Hexokinase activities determined by NADP cycling increased 20-fold while expression of GLUT1 assessed by micro-Western method 10-fold. GLUT1 expression was also analyzed by RT-PCR, which indicated that the expression is regulated at transcription level. There is a delay in the developmental changes in glucose uptake, hexokinase activity and GLUT1 expression when the embryos are developed in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Studies in oocyte maturation and embryonic development]. 837 Oct 11

Glycolysis is essential for cerebral energy generation. Hence, expression and regulation of gene-encoding brain hexokinase (HK I), the exclusive brain glucose phosphorylating enzyme, can be a critical step in this process. The present study demonstrates the ability of recombinant brain insulin-like growth factor (BIGF, a closely related member of insulin superfamily) to stimulate HK I gene expression in a concentration- and time-dependent manner in C6 glial cells. BIGF treatment (10 ng/ml) on quiescent C6 glial cells stimulates transcription and translation of HK I RNA to approximately 2.5-fold within 4 h after the addition of growth factor. In contrast, insulin or epidermal growth factor could not mimic this effect. Coincubation of cycloheximide with BIGF abolished this stimulatory effect, indicating a requirement for prior protein synthesis for this effect. These results suggest that IGF may have a role in regulating hexokinase gene expression in brain and possibly of brain glucose metabolism.
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PMID:Stimulation of brain hexokinase gene expression by recombinant brain insulin-like growth factor in C6 glial cells. 988 33

Breast cancers that express epidermal growth factor (EGF) receptors (EGFRs) are associated with poor prognosis. Our group recently showed in breast cancer patients that EGFR expression is strongly correlated with high tumor uptake of the glucose analogue, 18F-fluorodeoxyglucose (FDG). Here, we explored the cellular mechanism and signaling pathways that can explain the relation between EGFR and breast cancer cell glucose metabolism. FDG uptake, lactate production and hexokinase (HK) activity were measured, and proliferation assays and western blots were performed. EGF stimulated an increase of FDG uptake in EGFR-positive T47D and MDA-MB-468 cells, but not in MCF-7 cells. In T47D cells, the effect was dose-dependent and was accompanied by increased lactate production, indicating a shift toward glycolytic flux. This metabolic response occurred through enhanced HK activity and upregulated glucose transporter 1 (GLUT1) expression. EGFR stimulation also increased T47D cell proliferation. Blocking EGFR activation with BIBX1382 or gefitinib completely abolished both FDG uptake and proliferation effects. EGFR stimulation induced MAP kinase (MAPK) and PI3 kinase (PI3K) activation. Increased cell proliferation by EGFR stimulation was completely abolished by MAPK inhibition with PD98059 or by PI3K inhibition with LY294002. Increased FDG uptake was also completely abrogated by PI3K inhibition but was uninfluenced by MAPK inhibition. These findings suggest that the association between breast tumor EGFR expression and high FDG uptake might be contributed by stimulation of the PI3K pathway downstream of EGFR activation. This was in contrast to EGFR-mediated cell proliferation that required MAPK as well as PI3K signaling.
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PMID:EGF receptor stimulation shifts breast cancer cell glucose metabolism toward glycolytic flux through PI3 kinase signaling. 3153 71