| Kinetics of transport and phosphorylation of glucose in cancer cells. | |
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MedLine Citation:
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PMID: 19681047 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Metabolic control analysis of tumor glycolysis has indicated that hexokinase (HK) and glucose transporter (GLUT) exert the main flux control (71%). To understand why they are the main controlling steps, the GLUT and HK kinetics and the contents of GLUT1, GLUT2, GLUT3, GLUT4, HKI, and HKII were analyzed in rat hepatocarcinoma AS-30D and HeLa human cervix cancer. An improved protocol to determine the kinetic parameters of GLUT was developed with D-[2-(3)H-glucose] as physiological substrate. Kinetic analysis revealed two components at low- and high-glucose concentrations in both tumor cells. At low glucose and 37 degrees C, the V(max) was 55 +/- 20 and 17.2 +/- 6 nmol (min x mg protein)(-1), whereas the K(m) was 0.52 +/- 0.7 and 9.3 +/- 3 mM for hepatoma and HeLa cells, respectively. GLUT activity was partially inhibited by cytochalasin B (IC(50) = 0.44 +/- 0.1; K(i) = 0.3 +/- 0.1 microM) and phloretin (IC(50) = 8.7 microM) in AS-30D hepatocarcinoma. At physiological glucose, GLUT1 and GLUT3 were the predominant active isoforms in HeLa cells and AS-30D cells, respectively. HK activity in HeLa cells was much lower (60 mU/mg protein) than that in AS-30D cells (700 mU/mg protein), but both HKs were strongly inhibited by G6P. HKII was the predominant isoform in AS-30D carcinoma and HeLa cells. The much lower GLUT V(max) and catalytic efficiency (V(max)/K(m)) values in comparison to those of G6P-sensitive HK suggested the transporter exerts higher control on the glycolytic flux than HK in cancer cells. Thus, GLUT seems a more adequate therapeutic target. |
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Authors:
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Sara Rodríguez-Enríquez; Alvaro Marín-Hernández; Juan Carlos Gallardo-Pérez; Rafael Moreno-Sánchez |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of cellular physiology Volume: 221 ISSN: 1097-4652 ISO Abbreviation: J. Cell. Physiol. Publication Date: 2009 Dec |
Date Detail:
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Created Date: 2009-10-01 Completed Date: 2009-11-13 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0050222 Medline TA: J Cell Physiol Country: United States |
Other Details:
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Languages: eng Pagination: 552-9 Citation Subset: IM |
Affiliation:
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Departamento de Bioquímica, Instituto Nacional de Cardiología Ignacio Chávez, Tlalpan, México City, Mexico. sara.rodriguez@cardiologia.org.mx |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Biological Transport / drug effects Catalysis / drug effects Cell Line, Tumor Cell Proliferation Cold Temperature Cytochalasin B / pharmacology Cytosol / drug effects, metabolism Female Glucose / metabolism* Glucose Transport Proteins, Facilitative / antagonists & inhibitors, metabolism Glucose-6-Phosphate / pharmacology Glycolysis / physiology Hela Cells Hexokinase / analysis, metabolism Humans Insulin / pharmacology Isoenzymes / metabolism Kinetics Mitochondria / drug effects, metabolism Neoplasms / metabolism* Phloretin / pharmacology Phosphorylation Rats Rats, Wistar |
| Chemical | |
Reg. No./Substance:
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0/Glucose Transport Proteins, Facilitative; 0/Isoenzymes; 11061-68-0/Insulin; 14930-96-2/Cytochalasin B; 50-99-7/Glucose; 56-73-5/Glucose-6-Phosphate; 60-82-2/Phloretin; EC 2.7.1.1/Hexokinase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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