Current status and challenges in connecting models of erythrocyte metabolism to experimental reality

Detailed kinetic models of human erythrocyte metabolism have served to summarize the vast literature and to predict outcomes from laboratory and "Nature's" experiments on this simple cell. Mathematical methods for handling the large array of nonlinear ordinary differential equations that describe the time dependence of this system are well developed, but experimental methods that can guide the evolution of the models are in short supply. NMR spectroscopy is one method that is non-selective with respect to analyte detection but is highly specific with respect to their identification and quantification. Thus time courses of metabolism are readily recorded for easily changed experimental conditions. While the data can be simulated, the systems of equations are too complex to allow solutions of the inverse problem, namely parameter-value estimation for the large number of enzyme and membrane-transport reactions operating in situ as opposed to in vitro. Other complications with the modelling include the dependence of cell volume on time, and the rates of membrane transport processes are often dependent on the membrane potential. These matters are discussed in the light of new modelling strategies.