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Title: | HepatoDyn: a dynamic model of hepatocyte metabolism that integrates 13C isotopomer data |
Author: | Foguet Coll, Carles Marín Martínez, Silvia Selivanov, Vitaly Fanchon, Eric Lee, Paul Wai Nang Guinovart, Joan J. (Joan Josep), 1947- Atauri Carulla, Ramón de Cascante i Serratosa, Marta |
Keywords: | Hepatologia Isòtops Metabolisme Hepatology Isotopes Metabolism |
Issue Date: | 28-Apr-2016 |
Publisher: | Public Library of Science (PLoS) |
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. |
Note: | Reproducció del document publicat a: https://doi.org/10.1371/journal.pcbi.1004899 |
It is part of: | PLoS Computational Biology, 2016, vol. 12, num. 4, p. e1004899 |
URI: | http://hdl.handle.net/2445/104523 |
Related resource: | https://doi.org/10.1371/journal.pcbi.1004899 |
ISSN: | 1553-734X |
Appears in Collections: | Articles publicats en revistes (Bioquímica i Biomedicina Molecular) Publicacions de projectes de recerca finançats per la UE |
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