Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/24345
Title: Compartmentation of glycogen metabolism revealed from 13C isotopologue distributions
Author: Marin de Mas, Igor
Selivanov, Vitaly A.
Marín Martínez, Silvia
Roca Elias, Josep
Orešic, Matej
Agius, Loranne
Cascante i Serratosa, Marta
Keywords: Bioquímica clínica
Metabolisme
Clinical biochemistry
Metabolism
Issue Date: 28-Oct-2011
Publisher: BioMed Central
Abstract: Background: Stable isotope tracers are used to assess metabolic flux profiles in living cells. The existing methods of measurement average out the isotopic isomer distribution in metabolites throughout the cell, whereas the knowledge of compartmental organization of analyzed pathways is crucial for the evaluation of true fluxes. That is why we accepted a challenge to create a software tool that allows deciphering the compartmentation of metabolites based on the analysis of average isotopic isomer distribution. Results: The software Isodyn, which simulates the dynamics of isotopic isomer distribution in central metabolic pathways, was supplemented by algorithms facilitating the transition between various analyzed metabolic schemes, and by the tools for model discrimination. It simulated 13C isotope distributions in glucose, lactate, glutamate and glycogen, measured by mass spectrometry after incubation of hepatocytes in the presence of only labeled glucose or glucose and lactate together (with label either in glucose or lactate). The simulations assumed either a single intracellular hexose phosphate pool, or also channeling of hexose phosphates resulting in a different isotopic composition of glycogen. Model discrimination test was applied to check the consistency of both models with experimental data. Metabolic flux profiles, evaluated with the accepted model that assumes channeling, revealed the range of changes in metabolic fluxes in liver cells. Conclusions: The analysis of compartmentation of metabolic networks based on the measured 13C distribution was included in Isodyn as a routine procedure. The advantage of this implementation is that, being a part of evaluation of metabolic fluxes, it does not require additional experiments to study metabolic compartmentation. The analysis of experimental data revealed that the distribution of measured 13C-labeled glucose metabolites is inconsistent with the idea of perfect mixing of hexose phosphates in cytosol. In contrast, the observed distribution indicates the presence of a separate pool of hexose phosphates that is channeled towards glycogen synthesis.
Note: Reproducció del document publicat a: http://dx.doi.org/10.1186/1752-0509-5-175
It is part of: BMC Systems Biology 2011, 5:175
Related resource: http://dx.doi.org/10.1186/1752-0509-5-175
URI: http://hdl.handle.net/2445/24345
ISSN: 1752-0509
Appears in Collections:Publicacions de projectes de recerca finançats per la UE
Articles publicats en revistes (Bioquímica i Biomedicina Molecular)

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