Model of 2,3-bisphosphoglycerate metabolism in the human erythrocyte based on detailed enzyme kinetic equations1 : computer simulation and Metabolic Control Analysis

This is the third of three papers [see also Mulquiney, Bubb and Kuchel (1999) Biochem. J. 342, 565–578; Mulquiney and Kuchel (1999) Biochem. J. 342, 579–594] for which the general goal was to explain the regulation and control of 2,3-bisphosphoglycerate (2,3-BPG) metabolism in human erythrocytes. 2,3-BPG is a major modulator of haemoglobin oxygen affinity and hence is vital in blood oxygen transport. A detailed mathematical model of erythrocyte metabolism was presented in the first two papers. The model was refined through an iterative loop of experiment and simulation and it was used to predict outcomes that are consistent with the metabolic behaviour of the erythrocyte under a wide variety of experimental and physiological conditions. For the present paper, the model was examined using computer simulation and Metabolic Control Analysis. The analysis yielded several new insights into the regulation and control of 2,3-BPG metabolism. Specifically it was found that : (1) the feedback inhibition of hexokinase and phosphofructokinase by 2,3-BPG