HepatoDyn: a dynamic model of hepatocyte metabolism that integrates 13C isotopomer data

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 dy...

Descripción completa

Detalles Bibliográficos
Autores: 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
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2016
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/104523
Acceso en línea:https://hdl.handle.net/2445/104523
Access Level:acceso abierto
Palabra clave:Hepatologia
Isòtops
Metabolisme
Hepatology
Isotopes
Metabolism
id ES_7573dfd197bf16e3e6feea5d509047e6
oai_identifier_str oai:diposit.ub.edu:2445/104523
network_acronym_str ES
network_name_str España
repository_id_str
spelling HepatoDyn: a dynamic model of hepatocyte metabolism that integrates 13C isotopomer dataFoguet Coll, CarlesMarín Martínez, SilviaSelivanov, VitalyFanchon, EricLee, Paul Wai NangGuinovart, Joan J. (Joan Josep), 1947-Atauri Carulla, Ramón deCascante i Serratosa, MartaHepatologiaIsòtopsMetabolismeHepatologyIsotopesMetabolismThe 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.Public Library of Science (PLoS)2016info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/104523Articles publicats en revistes (Bioquímica i Biomedicina Molecular)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1371/journal.pcbi.1004899PLoS Computational Biology, 2016, vol. 12, num. 4, p. e1004899https://doi.org/10.1371/journal.pcbi.1004899info:eu-repo/grantAgreement/EC/FP7/222639cc-by (c) Foguet, Carles et al., 2016http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1045232026-05-27T06:46:51Z
dc.title.none.fl_str_mv HepatoDyn: a dynamic model of hepatocyte metabolism that integrates 13C isotopomer data
title HepatoDyn: a dynamic model of hepatocyte metabolism that integrates 13C isotopomer data
spellingShingle HepatoDyn: a dynamic model of hepatocyte metabolism that integrates 13C isotopomer data
Foguet Coll, Carles
Hepatologia
Isòtops
Metabolisme
Hepatology
Isotopes
Metabolism
title_short HepatoDyn: a dynamic model of hepatocyte metabolism that integrates 13C isotopomer data
title_full HepatoDyn: a dynamic model of hepatocyte metabolism that integrates 13C isotopomer data
title_fullStr HepatoDyn: a dynamic model of hepatocyte metabolism that integrates 13C isotopomer data
title_full_unstemmed HepatoDyn: a dynamic model of hepatocyte metabolism that integrates 13C isotopomer data
title_sort HepatoDyn: a dynamic model of hepatocyte metabolism that integrates 13C isotopomer data
dc.creator.none.fl_str_mv 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
author Foguet Coll, Carles
author_facet 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
author_role author
author2 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
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Hepatologia
Isòtops
Metabolisme
Hepatology
Isotopes
Metabolism
topic Hepatologia
Isòtops
Metabolisme
Hepatology
Isotopes
Metabolism
description 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.
publishDate 2016
dc.date.none.fl_str_mv 2016
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/104523
url https://hdl.handle.net/2445/104523
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1371/journal.pcbi.1004899
PLoS Computational Biology, 2016, vol. 12, num. 4, p. e1004899
https://doi.org/10.1371/journal.pcbi.1004899
info:eu-repo/grantAgreement/EC/FP7/222639
dc.rights.none.fl_str_mv cc-by (c) Foguet, Carles et al., 2016
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Foguet, Carles et al., 2016
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Public Library of Science (PLoS)
publisher.none.fl_str_mv Public Library of Science (PLoS)
dc.source.none.fl_str_mv Articles publicats en revistes (Bioquímica i Biomedicina Molecular)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869410981245878272
score 15,300719

Similares en LA Referencia