%0 Journal Article
%T Catabolic efficiency of aerobic glycolysis: The Warburg effect revisited
%A Alexei Vazquez
%A Jiangxia Liu
%A Yi Zhou
%A Zoltš¢n N Oltvai
%J BMC Systems Biology
%D 2010
%I BioMed Central
%R 10.1186/1752-0509-4-58
%X Here, we resolve this apparent contradiction by expanding the notion of metabolic efficiency. We study a reduced flux balance model of ATP production that is constrained by the glucose uptake capacity and by the solvent capacity of the cell's cytoplasm, the latter quantifying the maximum amount of macromolecules that can occupy the intracellular space. At low glucose uptake rates we find that mitochondrial respiration is indeed the most efficient pathway for ATP generation. Above a threshold glucose uptake rate, however, a gradual activation of aerobic glycolysis and slight decrease of mitochondrial respiration results in the highest rate of ATP production.Our analyses indicate that the Warburg effect is a favorable catabolic state for all rapidly proliferating mammalian cells with high glucose uptake capacity. It arises because while aerobic glycolysis is less efficient than mitochondrial respiration in terms of ATP yield per glucose uptake, it is more efficient in terms of the required solvent capacity. These results may have direct relevance to chemotherapeutic strategies attempting to target cancer metabolism.Since its original discovery by Warburg [1] it has been well established that most, if not all cancer cells are more dependent on aerobic glycolysis for ATP production than normal cells. The near uniform presence of this metabolic phenotype in tumor cells is counterintuitive, as glycolysis produces only 2 moles of ATP per mole of glucose, far less than the 36 generated by mitochondrial respiration (Figure 1). Several hypotheses have been proposed for the maintenance of this seemingly wasteful catabolic state. At the cell population level, mitochondrial respiration malfunction and enhancement of glycolysis are thought to be a metabolic advantage under the intermittent hypoxia conditions experienced by pre-malignant and malignant tumor cells [2,3]. However, aerobic glycolysis is not found exclusively in cancer cells, but is also observed in rapidly dividing n
%U http://www.biomedcentral.com/1752-0509/4/58