Catabolic efficiency of aerobic glycolysis: The Warburg effect revisited
By A. Vázquez, Jiangxia Liu, Yi Zhou, Zoltn Oltvai. BMC Systems Biology, 2010
327 citations recorded by the source corpus.
BackgroundCancer cells simultaneously exhibit glycolysis with lactate secretion and mitochondrial respiration even in the presence of oxygen, a phenomenon known as the Warburg effect. The maintenance of this mixed metabolic phenotype is seemingly counterintuitive given that aerobic glycolysis is far less efficient in terms of ATP yield per moles of glucose than mitochondrial respiration.ResultsHere, 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.ConclusionsOur 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.
Subfields: Cancer Research, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/3a7d4cd16cd1ccc4bf23a811a1c55bb04ad7a16a
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Citations in the corpus
- The Warburg Effect: How Does it Benefit Cancer Cells? (2016, background): “Another scenario of such a tradeoff comes from the idea that the physical volume available per cell may limit mitochondria number and thus any energy and biomass that exceed the limited mitochondrial capacity needs to be produced from aerobic glycolysis [36-38].”