ArticleBMC systems biology2011
Compartmentation of glycogen metabolism revealed from 13C isotopologue distributions.
Article in BMC systems biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 30 citations in OpenAlex.
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- The landscape of tiered regulation of breast cancer cell metabolism.Scientific reports · 2019Article
- How glycogen sustains brain function: A plausible allosteric signaling pathway mediated by glucose phosphates.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2019Review
- From correlation to causation: analysis of metabolomics data using systems biology approaches.Metabolomics : Official journal of the Metabolomic Society · 2018Review
- Chloroformate derivatization for tracing the fate of Amino acids in cells and tissues by multiple stable isotope resolved metabolomics (mSIRM).Analytica chimica acta · 2017Article
- Protein-protein interactions and metabolite channelling in the plant tricarboxylic acid cycle.Nature communications · 2017Article
- MIDcor, an R-program for deciphering mass interferences in mass spectra of metabolites enriched in stable isotopes.BMC bioinformatics · 2017Article
- Unveiling the Metabolic Changes on Muscle Cell Metabolism UnderlyingFrontiers in molecular biosciences · 2017Article
- HepatoDyn: A Dynamic Model of Hepatocyte Metabolism That Integrates 13C Isotopomer Data.PLoS computational biology · 2016Article
- (13)C metabolic flux analysis shows that resistin impairs the metabolic response to insulin in L6E9 myotubes.BMC systems biology · 2014Article
- 'Isotopo' a database application for facile analysis and management of mass isotopomer data.Database : the journal of biological databases and curation · 2014Article
- Kinetic modelling of phospholipid synthesis in Plasmodium knowlesi unravels crucial steps and relative importance of multiple pathways.BMC systems biology · 2013Article
Corrections and comments
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Authors and funding
7 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundStable 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.
resultsThe 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.
conclusionsThe 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.
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