title: HepatoDyn: A Dynamic Model of Hepatocyte Metabolism That Integrates 13C Isotopomer Data.
abstract: The liver performs many essential metabolic functions, which can be studied using computational models of hepatocytes. Here we present HepatoDyn, a highly detailed dynamic model of hepatocyte metabolism. HepatoDyn includes a large metabolic network, highly detailed kinetic laws, and is capable of dynamically simulating the redox and energy metabolism of hepatocytes. Furthermore, the model was coupled to the module for isotopic label propagation of the software package IsoDyn, allowing HepatoDyn to integrate data derived from 13C based experiments. As an example of dynamical simulations applied to hepatocytes, we studied the effects of high fructose concentrations on hepatocyte metabolism by integrating data from experiments in which rat hepatocytes were incubated with 20 mM glucose supplemented with either 3 mM or 20 mM fructose. These experiments showed that glycogen accumulation was significantly lower in hepatocytes incubated with medium supplemented with 20 mM fructose than in hepatocytes incubated with medium supplemented with 3 mM fructose. Through the integration of extracellular fluxes and 13C enrichment measurements, HepatoDyn predicted that this phenomenon can be attributed to a depletion of cytosolic ATP and phosphate induced by high fructose concentrations in the medium.
authors.affiliation: Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, Universitat de Barcelona, Barcelona, Spain.|Institute of Biomedicine of Universitat de Barcelona (IBUB) and Associated Unit to CSIC, Barcelona, Spain.
authors.forename: Carles
authors.initials: C
authors.lastname: Foguet
authors.affiliation: Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, Universitat de Barcelona, Barcelona, Spain.|Institute of Biomedicine of Universitat de Barcelona (IBUB) and Associated Unit to CSIC, Barcelona, Spain.
authors.forename: Silvia
authors.identifier: 0000-0003-0693-2207
authors.initials: S
authors.lastname: Marin
authors.affiliation: Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, Universitat de Barcelona, Barcelona, Spain.|Institute of Biomedicine of Universitat de Barcelona (IBUB) and Associated Unit to CSIC, Barcelona, Spain.
authors.forename: Vitaly A
authors.initials: VA
authors.lastname: Selivanov
authors.affiliation: UGA - CNRS, TIMC-IMAG UMR 5525, Grenoble, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Fanchon
authors.affiliation: Department of Pediatrics, Los Angeles Biomedical Research Institute, Torrance, California, United States of America.
authors.forename: Wai-Nang Paul
authors.identifier: 0000-0002-0128-9112
authors.initials: WN
authors.lastname: Lee
authors.affiliation: Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, Universitat de Barcelona, Barcelona, Spain.|Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain.
authors.forename: Joan J
authors.initials: JJ
authors.lastname: Guinovart
authors.affiliation: Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, Universitat de Barcelona, Barcelona, Spain.|Institute of Biomedicine of Universitat de Barcelona (IBUB) and Associated Unit to CSIC, Barcelona, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: de Atauri
authors.affiliation: Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, Universitat de Barcelona, Barcelona, Spain.|Institute of Biomedicine of Universitat de Barcelona (IBUB) and Associated Unit to CSIC, Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Cascante
mesh_terms: D000818:Animals; D002247:Carbon Isotopes; D019295:Computational Biology; D003198:Computer Simulation; D005632:Fructose / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D053858:Metabolic Networks and Pathways; D008954:Models, Biological; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002247:Carbon Isotopes; D005632:Fructose; D005947:Glucose