Hypoxia-induced alterations in metabolism: predictions using the mathematical model and measurements by CE-MS. A) 3 min-hypoxia-induced alterations in predicted activities (left), predicted metabolite concentrations (middle) and metabolite concentrations determined by CE-MS analysis (right) where closed circles indicate ratios of hypoxic metabolite concentrations to normoxic control concentrations represented with open circles. The boxed graphs in the left line indicate the hypoxia-induced changes in energy charge and total amount of 2,3-BPG. The simulation results using the BIII(+) model were shown in solid lines and those using the BIII() model in doted lines. B) Hypoxia-induced acceleration of glycolysis assessed by pulse-chace analysis of the conversion of ¹³C-glucose into ¹³C-lactate and its blockade by CO. Each bar indicates relative amounts of ¹³C-lactate converted per 1 min after loading with ¹³C-glucose at 5mM under normoxic (N) and hypoxic (H) conditions. CO() and CO(+) indicate erythrocytes pretreated without and with CO, respectively. C) Prediction of beneficial effects of enzyme-BIII interaction in changes in energy charge (upper graph) and total amount of 2,3-BPG (lower graph). Each line indicates the results under different hypoxic conditions when the amounts of the following enzymes were increased by 2-fold, PFK, HK, PK and their combinations, in corresponding line types shown in the upper box. Experimental values are the mean ± S.E. (n = 4). Asterisks, p < 0.05 versus the base-line values.