Figure 6. A unified model of aerobic glycolysis.
A unified picture of flux control in aerobic glycolysis. (left) Under conditions where there is an accumulation of intermediates in upper glycolysis and depletion of intermediates in lower glycolysis a bottleneck exists at the step involving GAPDH. This bottleneck is due to the status of energy and redox metabolism and the thermodynamics of the pathway that together mediate the flux through GAPDH. As a result, inhibiting flux through glycolysis is most sensitive to a perturbation in GAPDH activity. (right) Under conditions where the metabolites in glycolysis are distributed more evenly with levels together being either high or low, no such bottleneck exists. Instead flux through glycolysis leading to lactate production is most determined by the canonical pacemaking steps in glycolysis involving PFK and HK. The relative levels of glycolytic intermediates are denoted by the size of the text.