Characterization of intracellular metabolic states in cells presenting the Warburg phenotype

- Cancer cells have been shown to undergo a metabolic reprogramming (Warburg effect) characterized by enhanced glycolytic fluxes and down-regulated oxidative phosphorylation even in the presence of abundant oxygen. - Experiments show that disruption of expression of enzymes that contribute to the enhancement of this glycolytic flux stimulates oxidative phosphorylation and leads to a decrease in tumor cell proliferation opening the way to the investigation of new therapeutic targets. - To date, the mechanistic details of this metabolic reprogramming, and in particular the physiological conditions that lead to the activation of this metabolic switch, have not been well characterized. - We apply thermodynamic-based metabolic flux balance analysis (TFBA) on a model of central carbon metabolism of mammalian cells in order to characterize thermodynamically feasible intracellular flux states associated with Warburg phenotype based on a pre-selected set of metabolic objectives.