Determining and understanding the control of glycolysis in fast-growth tumor cells. Flux control by an over-expressed but strongly product-inhibited hexokinase

The FEBS Journal
Alvaro Marín-HernándezRafael Moreno-Sánchez

Abstract

Control analysis of the glycolytic flux was carried out in two fast-growth tumor cell types of human and rodent origin (HeLa and AS-30D, respectively). Determination of the maximal velocity (V(max)) of the 10 glycolytic enzymes from hexokinase to lactate dehydrogenase revealed that hexokinase (153-306 times) and phosphofructokinase-1 (PFK-1) (22-56 times) had higher over-expression in rat AS-30D hepatoma cells than in normal freshly isolated rat hepatocytes. Moreover, the steady-state concentrations of the glycolytic metabolites, particularly those of the products of hexokinase and PFK-1, were increased compared with hepatocytes. In HeLa cells, V(max) values and metabolite concentrations for the 10 glycolytic enzyme were also significantly increased, but to a much lesser extent (6-9 times for both hexokinase and PFK-1). Elasticity-based analysis of the glycolytic flux in AS-30D cells showed that the block of enzymes producing Fru(1,6)P2 (i.e. glucose transporter, hexokinase, hexosephosphate isomerase, PFK-1, and the Glc6P branches) exerted most of the flux control (70-75%), whereas the consuming block (from aldolase to lactate dehydrogenase) exhibited the remaining control. The Glc6P-producing block (glucose transporter and hex...Continue Reading

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Citations

Feb 22, 2012·Archives of Toxicology·Alvaro Marín-HernándezSara Rodríguez-Enríquez
Jun 7, 2007·Journal of Bioenergetics and Biomembranes·Zhao ChenPeng Huang
Jul 28, 2012·Journal of Bioenergetics and Biomembranes·Tuuli KaambreValdur Saks
Aug 24, 2012·Current Opinion in Oncology·Kehinde AdekolaMala Shanmugam
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Dec 3, 2010·PloS One·Aleksandra Usenik, Matic Legiša
Feb 4, 2014·PloS One·Maria José Ramírez-BajoMarta Cascante
Sep 28, 2013·Journal of Bioenergetics and Biomembranes·Aleksandr KlepininTuuli Kaambre
May 6, 2014·Archives of Toxicology·Sara Rodríguez-EnríquezRafael Moreno-Sánchez
Jul 17, 2008·Journal of Biomedicine & Biotechnology·Rafael Moreno-SánchezViridiana Olín-Sandoval
Aug 2, 2008·PPAR Research·James M PhangYongmin Liu
Feb 11, 2012·Journal of Bioenergetics and Biomembranes·Clara Rodrigues-FerreiraAntonio Galina
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Sep 21, 2010·Aquatic Toxicology·Ricardo Jasso-ChávezRafael Moreno-Sánchez
Jul 6, 2010·Mitochondrion·Rafael Moreno-SánchezHans V Westerhoff
Oct 6, 2015·Biochimica Et Biophysica Acta·Ileana Hernández-ReséndizSara Rodríguez-Enríquez
May 19, 2009·BioFactors·Rafael Moreno-SánchezJuan Carlos Gallardo-Pérez
Jan 6, 2009·Molecular Nutrition & Food Research·Sara Rodríguez-EnríquezRafael Moreno-Sánchez
Sep 11, 2007·The FEBS Journal·Emma SaavedraRafael Moreno-Sánchez
Feb 12, 2008·Journal of Cellular Physiology·Sara Rodríguez-EnríquezRafael Moreno-Sánchez
Jun 12, 2012·ChemMedChem·Carlotta Granchi, Filippo Minutolo
Jun 17, 2011·Journal of Cellular Biochemistry·Sara Rodríguez-EnríquezRafael Moreno-Sánchez
Mar 18, 2016·British Journal of Cancer·Liat Edry BotzerIsaac P Witz
Aug 15, 2009·Journal of Cellular Physiology·Sara Rodríguez-EnríquezRafael Moreno-Sánchez
Nov 30, 2010·Biochimica Et Biophysica Acta·Alvaro Marín-HernándezEmma Saavedra
Apr 14, 2016·Biochimica Et Biophysica Acta·Noureddine HammadAnne Devin
Feb 12, 2014·The International Journal of Biochemistry & Cell Biology·Rafael Moreno-SánchezSara Rodríguez-Enríquez
Dec 1, 2012·Biochimica Et Biophysica Acta·Edna Ayerim Mandujano-TinocoSara Rodríguez-Enríquez
Jul 27, 2010·The International Journal of Biochemistry & Cell Biology·Sara Rodríguez-EnríquezRafael Moreno-Sánchez

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