Computational Modeling of the Metabolic States Regulated by the Kinase Akt
| Autor: | Annamaria Bevilacqua, Luciano Milanesi, Gianfranco Canti, Carlo Maj, Roberta Alfieri, Ettore Mosca |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Physiology
kinetic models Biology Pentose phosphate pathway mTORC2 lcsh:Physiology 03 medical and health sciences 0302 clinical medicine Physiology (medical) PI3K/AKT/mTOR cancer Glycolysis Protein kinase B PI3K/AKT/mTOR pathway 030304 developmental biology Original Research 0303 health sciences lcsh:QP1-981 Kinase RPTOR kinetic model glycolysis PI3K/Akt/mTOR pathway Cell biology Biochemistry Anaerobic glycolysis 030220 oncology & carcinogenesis metabolism |
| Zdroj: | Frontiers in Physiology, Vol 3 (2012) Frontiers in Physiology Frontiers in physiology 3 (2012): 418. doi:10.3389/fphys.2012.00418 info:cnr-pdr/source/autori:Mosca, Ettore; Alfieri, Roberta; Maj, Carlo; Bevilacqua, Annamaria; Canti, Gianfranco; Milanesi, Luciano/titolo:Computational modeling of the metabolic States regulated by the kinase akt./doi:10.3389%2Ffphys.2012.00418/rivista:Frontiers in physiology/anno:2012/pagina_da:418/pagina_a:/intervallo_pagine:418/volume:3 |
| ISSN: | 1664-042X |
| DOI: | 10.3389/fphys.2012.00418 |
| Popis: | Signal transduction pathways 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 modelled the link between the PI3K/Akt/mTOR pathway, glycolysis, lactic acid production and nucleotide biosynthesis. We used a computational model in order to compare two metabolic states generated by the specific variation of the metabolic fluxes regulated by the activity of the PI3K/Akt/mTOR pathway. One of the two states represented the metabolism of a growing cancer cell characterised by aerobic glycolysis and cellular biosynthesis, while the other state represented the same metabolic network with a reduced glycolytic rate and a higher mitochondrial pyruvate metabolism, as reported in literature in relation to the activity of the PI3K/Akt/mTOR. Some steps that link glycolysis and pentose phosphate pathway revealed their importance for controlling the dynamics of cancer glucose metabolism. |
| Databáze: | OpenAIRE |
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