TY - JOUR
T1 - Computational modeling of the metabolic states regulated by the kinase Akt
AU - Mosca, Ettore
AU - Alfieri, Roberta
AU - Maj, Carlo
AU - Bevilacqua, Annamaria
AU - Canti, Gianfranco
AU - Milanesi, Luciano
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
KW - Cancer
KW - Glycolysis
KW - Kinetic models
KW - Metabolism
KW - PI3K/Akt/mTOR pathway
UR - http://www.scopus.com/inward/record.url?scp=84870942283&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84870942283&partnerID=8YFLogxK
U2 - 10.3389/fphys.2012.00418
DO - 10.3389/fphys.2012.00418
M3 - Article
C2 - 23181020
AN - SCOPUS:84870942283
VL - 3 NOV
JO - Frontiers in Physiology
JF - Frontiers in Physiology
SN - 1664-042X
M1 - Article 418
ER -