Exploring the Altered Dynamics of @entity1 Central XXXX Metabolic Pathway in Cancer Cells: A Classical Control Theoretic Approach.

@entity1 @entity5 @entity36435 @entity880 @entity505 @entity2388 @entity413 @entity855
BACKGROUND: In contrast with normal cells, most of the @entity5 cells depend on aerobic glycolysis for energy production in the form of @entity855 ( @entity855 ) bypassing mitochondrial oxidative phosphorylation. Moreover, compared to normal cells, @entity5 cells exhibit higher consumption of @entity413 with higher production of @entity880 . Again, higher rate of glycolysis provides the necessary glycolytic intermediary precursors for DNA, protein and lipid synthesis to maintain high active proliferation of the @entity5 cells. In this scenario, classical control theory based approach may be useful to explore the altered dynamics of the @entity5 cells. Since the dynamics of the @entity5 cells is different from that of the normal cells, understanding their dynamics may lead to development of novel therapeutic strategies. METHOD: We have developed a model based on the state space equations of classical control theory along with an order reduction technique to mimic the actual dynamic behavior of @entity1 central @entity505 metabolic (CCM) pathway in normal cells. Here, we have modified Michaelis Menten kinetic equation to incorporate feedback mechanism along with perturbations and cross talks associated with a metabolic pathway. Furthermore, we have perturbed the proposed model to reduce the mitochondrial oxidative phosphorylation. Thereafter, we have connected proportional-integral (PI) controller(s) with the model for tuning it to behave like the CCM pathway of a @entity5 cell. This methodology allows one to track the altered dynamics mediated by different enzymes. RESULTS AND DISCUSSIONS: The proposed model successfully mimics all the probable dynamics of the CCM pathway in normal cells. Moreover, experimental results demonstrate that in @entity5 cells, a coordination among enzymes catalyzing @entity36435 pathway and intermediate glycolytic enzymes along with switching of @entity2388 kinase (M2 isoform) plays an important role to maintain their altered dynamics.
