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)

Astrocytes play a well-established role in brain metabolism, being a key element in the capture of energetic compounds from the circulation and in their delivery to active neurons. Their metabolic status is affected in many pathological situations, such as gliomas, which are the most common brain tumors. This proliferative dysfunction is associated with changes in gap junctional communication, a property strongly developed in normal astrocytes studied both in vitro and in vivo. Here, we summarize and discuss the findings that have lead to the identification of a link between gap junctions, glucose uptake, and proliferation. Indeed, the inhibition of gap junctional communication is associated with an increase in glucose uptake due to a rapid change in the localization of both GLUT-1 and type I hexokinase. This effect persists due to the up-regulation of GLUT-1 and type I hexokinase and to the induction of GLUT-3 and type II hexokinase. In addition, cyclins D1 and D3 have been found to act as sensors of the inhibition of gap junctions and have been proposed to play the role of mediators in the mitogenic effect observed. Conversely, in C6 glioma cells, characterized by a low level of intercellular communication, an increase in gap junctional communication reduces glucose uptake by releasing type I and type II hexokinases from the mitochondria and decreases the exacerbated rate of proliferation due to the up-regulation of the Cdk inhibitors p21 and p27. Identification of the molecular actors involved in these pathways should allow the determination of potential therapeutic targets that could lead to the testing of alternative strategies to prevent, or at least slow down, the proliferation of glioma cells.
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PMID:Glucose metabolism and proliferation in glia: role of astrocytic gap junctions. 1689 68

We examined the possible implication of ras in the regulation of the activity of several metabolic enzymes by employing an inducible H-ras expression system (RFLSVrasLAP cell line), in which the addition of IPTG decreases the levels of ras p21 3-fold. We measured the activity of hexokinase (E.C. 2.7.1.1.), glucose phosphate isomerase (E.C. 5.3.1.9), phospho-fructokinase (E.C. 2.7.1.11), aldolase (E.C. 4.1.2.13), phosphoglycerate kinase (E.C. 2.7.2.3), enolase (E.C. 4.2.1.11), pyruvate kinase (E.C. 2.7.1.40), lactate dehydrogenase (E.C. 1.1.1.27), adenosine deaminase (E.C. 3.5.4.4) and purine nucleoside phosphorylase (E.C. 2.4.2.1) from cells grown in the presence and absence of IPTG. We found that the addition of IPTG to RFLSVrasLAP cells led to lower activity of phosphoglycerate kinase (p=0.004), enolase (p=0.027) and pyruvate kinase (p=0.031). Enolase mRNA levels were found to be increased in cells overexpressing either the normal or mutant H-ras. The total rate of glycolysis was not affected by H-ras expression indicating that the implication of H-ras in the activity of phosphoglycerate kinase, enolase and pyruvate kinase may be associated with glycolysis-independent functions of these enzymes. Adenosine deaminase activity was found to increase after IPTG addition (P=0.009), indicating also a possible role for H-ras in the control of the purine nucleotide salvage pathway.
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PMID:T24 h-ras gene-expression increases the activity of phosphoglycerate kinase, enolase and pyruvate-kinase and decreases the activity of adenosine-deaminase in fibroblast cells. 2160 14

2-Deoxyglucose (2DG) is an anticancer drug with excellent safety profile. Because of its higher dose requirements, its potential is yet to translate into a monotherapy. However, recently, 2DG has been tested as an adjunct in established chemotherapeutic regimens. 2DG enhanced the potency of several chemotherapeutic agents but not all. The rationale selection of known chemotherapeutic agents to use with 2DG is hampered because of the lack of complete understanding of mechanism behind 2DG anticancer effects. Although, 2DG is a well-known glycolytic inhibitor, which inhibits the key glycolytic enzyme hexokinase, its anticancer effects cannot be fully explained by this simplistic mechanism alone. In this article, we have shown for the first time that 2DG induced a transient expression of p21 and a continuous expression of p53 in colorectal cancer cells (SW620). The treatment also caused cell cycle arrest at G0/G1 phase and induced apoptosis through the mitochondrial pathway. The effects of 2DG on p21 and p53 protein levels were totally independent of its inhibitory effect on either hexokinase or ATP levels. Results from this study provides key insights into novel molecular mechanisms of 2DG and directs rational selection of other anticancer drugs to combine with 2DG in colorectal cancer treatment.
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PMID:2-Deoxyglucose induces cell cycle arrest and apoptosisin colorectal cancer cells independent of its glycolysis inhibition. 2575 8