A Metabolic Model of Human Erythrocytes: Practical Application of the E-Cell Simulation Environment
Figure 3
Temporal alterations in glycolysis in response to hypoxia. (a) Predicted alterations in glycolytic enzyme activities under hypoxia and comparison of time-courses of glycolytic intermediates between the simulations and metabolome measurements using CE-MS. The simulation results of model A (including Band 3 interactions, corresponding to the solid red line in Figure 2 of [11]), model B (using the same initial steady-state conditions as A but neglecting further Band 3 interactions, corresponding to the dotted blue line in Figure 2 of [11]), and model C (with all enzymes dissociated from Band 3) are represented by the solid black (model A), dotted black (model B), and solid gray (model C) lines, respectively. See the main text for discussion of the models. In the metabolome data collected by CE-MS, closed circles indicate ratios of hypoxic metabolite concentrations to normoxic control concentrations, which are represented with open circles. Values are the means SE of four separate experiments. Asterisks: versus the steady-state baseline values. (b) Results of model analysis to determine whether or not increasing the activity of a particular enzyme (HK, PK, or PFK+ALD+GAPDH) by 2-fold can promote a simultaneous increase in the energy charge and in 2,3-BPG under conditions of hypoxia.
