tailieunhanh - Báo cáo khoa học: Determining and understanding the control of glycolysis in fast-growth tumor cells Flux control by an over-expressed but strongly product-inhibited hexokinase

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, respect-ively). Determination of the maximal velocity (Vmax) of the 10 glycolytic enzymes from hexokinase to lactate dehydrogenase revealed that hexokin-ase (153–306 times) and phosphfructokinase-1 (PFK-1) (22–56 times) had higher over-expression in rat AS-30D hepatoma cells than in normal freshly isolated rat hepatocytes. | ềFEBS Journal Determining and understanding the control of glycolysis in fast-growth tumor cells Flux control by an over-expressed but strongly product-inhibited hexokinase Alvaro Marin-Hernandez1 Sara Rodriguez-Enriquez1 Paola A. Vital-Gonzalez1 Fanny L. Flores-Rodriguez1 Marina Macias-Silva2 Marcela Sosa-Garrocho2 and Rafael Moreno-Sanchez1 1 Institute Nacionalde Cardiologia Departamento de Bioquimica Juan Badiano no. 1 Colonia Seccion XVI Mexico Mexico 2 Instituto de Fisiologia Celular Departamento de Biologia Celular Universidad NacionalAutonoma de Mexico Mexico Keywords elasticity coefficient flux-controlcoefficient hexokinase type 2 metabolic control analysis phosphofructokinase type 1 Correspondence R. Moreno-Sanchez Instituto Nacionalde Cardiologia Departamento de Bioquimica Juan Badiano no. 1 Col. Seccion XVI Tlalpan Mexico 14080 Mexico Fax 52 55 55730926 Tel 52 55 55732911 ext. 1422 1298 E-mail morenosanchez@ Received 17 October 2005 revised 21 February 2006 accepted 3 March 2006 doi 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 Vmax of the 10 glycolytic enzymes from hexokinase to lactate dehydrogenase revealed that hexokin-ase 153-306 times and phosphfructokinase-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 hexo-kinase and PFK-1 were increased compared with hepatocytes. In HeLa cells Vmax 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 .