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Determining and Understanding the Control of Glycolysis in Fast-Growth Tumor Cells

Flux Control by an Over-expressed but Strongly Product-Inhibited Hexokinase

Authors: Alvaro Marín-Hernández, Sara Rodríguez-Enríquez, Paola A. Vital-González, Fanny L. Flores-Rodríguez, Marina Macías-Silva, Marcela Sosa-Garrocho, and Rafael Moreno-Sánchez

Field: Biochemistry, Cell Biology

Document Summary: This study investigates the control of glycolytic flux in fast-growing tumor cells, specifically HeLa and AS-30D cell lines, by analyzing enzyme activities, metabolite concentrations, and applying metabolic control analysis. The research identifies hexokinase as a key regulatory enzyme in these tumor cells, despite its over-expression, due to strong product inhibition by glucose-6-phosphate (Glc6P). The findings highlight that the enhanced glycolytic flux in tumor cells is significantly influenced by the kinetic properties and regulatory mechanisms of hexokinase.

Detailed Table of Contents:

  • Keywords
  • Correspondence
  • Abstract
  • Introduction
  • Results: Maximal activities of glycolytic enzymes in hepatocytes and fast-growth tumor cells
  • Results: Glycolytic flux and intermediary concentrations
  • Results: Determination of flux control coefficients for glycolysis in hepatoma cells
  • Results: Experimental determination of elasticity coefficients for glycolytic intermediates in tumor cells
  • Results: Control (C) and elasticity (ε) coefficients values of AS-30D hepatoma cells
  • Results: Distribution of control of glycolysis in AS-30D cells
  • Results: Tumoral hexokinase and PFK-1 kinetic parameters
  • Discussion: Distribution of glycolytic flux control
  • Discussion: Biochemical mechanisms underlying the evaluated distribution of flux control
  • Experimental procedures: Chemicals
  • Experimental procedures: Isolation of tumor and liver cells
  • Experimental procedures: Determination of steady-state concentrations of metabolites
  • Experimental procedures: Determination of intracellular glucose
  • Experimental procedures: Determination of glycolytic flux in liver and tumor cells
  • Experimental procedures: Cell extracts of tumor and liver cells
  • Experimental procedures: Determination of flux control coefficients
  • Acknowledgements
  • References