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Mosca2012 - Central Carbon Metabolism Regulated by AKT

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SBML (L2V4)
Related Publication
  • Computational modeling of the metabolic States regulated by the kinase akt.
  • Mosca E, Alfieri R, Maj C, Bevilacqua A, Canti G, Milanesi L
  • Frontiers in physiology , 0/ 2012 , Volume 3 , pages: 418
  • Institute for Biomedical Technologies, Consiglio Nazionale delle Ricerche Segrate Milano, Italy.
  • Signal transduction and gene regulation determine a major reorganization of metabolic activities in order to support cell proliferation. Protein Kinase B (PKB), also known as Akt, participates in the PI3K/Akt/mTOR pathway, a master regulator of aerobic glycolysis and cellular biosynthesis, two activities shown by both normal and cancer proliferating cells. Not surprisingly considering its relevance for cellular metabolism, Akt/PKB is often found hyperactive in cancer cells. In the last decade, many efforts have been made to improve the understanding of the control of glucose metabolism and the identification of a therapeutic window between proliferating cancer cells and proliferating normal cells. In this context, we have modeled the link between the PI3K/Akt/mTOR pathway, glycolysis, lactic acid production, and nucleotide biosynthesis. We used a computational model to compare two metabolic states generated by two different levels of signaling through the PI3K/Akt/mTOR pathway: one of the two states represents the metabolism of a growing cancer cell characterized by aerobic glycolysis and cellular biosynthesis, while the other state represents the same metabolic network with a reduced glycolytic rate and a higher mitochondrial pyruvate metabolism. Biochemical reactions that link glycolysis and pentose phosphate pathway revealed their importance for controlling the dynamics of cancer glucose metabolism.
Contributors
Ettore Mosca

Metadata information

Curation status
Curated
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Model files

BIOMD0000000426.xml.origin SBML L2V4 representation of Mosca2012 - Central Carbon Metabolism Regulated by AKT 233.51 KB Preview | Download

  • Model originally submitted by : Ettore Mosca
  • Submitted: Oct 15, 2012 10:07:51 AM
  • Last Modified: Oct 9, 2014 6:31:01 PM
Revisions
  • Version: 2 public model Download this version
    • Submitted on: Oct 9, 2014 6:31:01 PM
    • Submitted by: Ettore Mosca
    • With comment: Current version of Mosca2012 - Central Carbon Metabolism Regulated by AKT
  • Version: 1 public model Download this version
    • Submitted on: Oct 15, 2012 10:07:51 AM
    • Submitted by: Ettore Mosca
    • With comment: Original import of Central Carbon Metabolism Regulated by AKT
Curator's comment:
(added: 14 Nov 2012, 16:09:15, updated: 14 Nov 2012, 16:09:15)
The model compares two metabolic states generated by the specific variation of the fluxes regulated by the activity of the PI3K/Akt/mTOR pathway. One state represents the metabolism of a growing cancer cell characterised by aerobic glycolysis and cellular biosynthesis (condition H), while the other (condition L) represented the same metabolic network with a reduced glycolytic rate, a reduced lactic acid production, but a higher mitochondrial pyruvate metabolism, in relation to a lower activity of PI3K/Akt/mTOR. Here, the model parameters corresponds to condition H (high PI3K/Akt/mTOR activity) and the table reproducing the corresponding metabolic fluxes (reported in the Appendix of the paper) has been obtained using Copasi v4.8 (Build 35).