Title: Analysis and simulation of metabolic networks: Application to HEPG2
Authors: ZALDIVAR COMENGES Jose'STROZZI F.
Publisher: Publications Office of the European Union
Publication Year: 2010
JRC N°: JRC61087
ISBN: 978-92-79-17118-5
ISSN: 1018-5593
Other Identifiers: EUR 24553 EN
OPOCE LB-NA-24553-EN-C
URI: http://publications.jrc.ec.europa.eu/repository/handle/JRC61087
DOI: 10.2788/30083
Type: EUR - Scientific and Technical Research Reports
Abstract: Chemical toxicity in most of the cases has a metabolic component and metabolic pathways are the most studied biochemical reactions. For these reasons we have started to analyze modelling approaches for studying toxicity at molecular level using the metabolism and focusing in HepG2 cell lines. Two approaches have been investigated. The first consists on the analysis of metabolic fluxes in HepG2 under different toxicants concentrations by complex network analysis tools. This is important when a correlation between dose-response curves and metabolomic data has to be established. The second approach is based on the development and application of a simplified dynamic model of metabolism. This approach requires the specification of the biochemical reactions as well as their kinetic parameters and, therefore, at the moment, the degree of detail in the description of HepG2 metabolism is reduced. The results suggest that a combined approach starting from metabolic fluxes and then solving the kinetic equations as our experimental data and knowledge of metabolic pathways increases is the most promising avenue to develop a quantitative approach of toxicity at molecular level. In addition, there is the necessity to link the molecular level approach with the cell growth and mortality with an intermediate level that translates metabolism changes into measurable parameters in cell-based assays.
JRC Institute:Institute for Health and Consumer Protection

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