Tumor cell energy metabolism and the role of AMPK in regulating the glycolytic and oxidative phosphorylation pathways

This study is based on the hypothesis that AMPK is a tumor suppressor protein and activation of AMPK in a cancer cell helps to reverse the Warburg effect. To test this hypothesis a computational model has been developed. If AMPK is active in a cancer cell, it phosphorylates and inactivates a number of metabolic enzymes to down-regulate glycolysis and up-regulate oxidative phosphorylation. It is shown that the activation of AMPK opposes the changes induced by the Warburg effect in a cancer cell. The concentrations of pyruvate and lactate, which are higher in a cancer cell, tend to go down towards levels present in a normal cell. As expected, the results show a decreased flux through glycolysis with AMPK activation,. The computational model successfully describes the metabolic hallmark of cancer and explains the metabolic role of AMPK as a tumor suppressor. The model contributes to the identification of important reaction in the metabolic pathways of tumor cell energy metabolism