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

Abstract

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.

Stability of open pathways

“…The complete system given by Kuchel et al [9] is more complicated. Our counterexample, Figure 2(a), shows that systems can be unstable.…”

“…This type of reaction scheme can be found in the galactose pathway which runs into the glycolytic pathway in human erythrocyte metabolism Figure 3 [9]. We consider a situation where glycose is supplied but galactose is not.…”

“…Again, this example is drawn from the human erythrocyte metabolism, if we look to the glycolytic pathway Figure 3 [9]. The section of the pathway with this structure is the 1,3-BGP/2,3-BPG/3-PGA interaction:…”

“…This scheme represents the human erythrocyte glycolytic pathway. We show a reduced version of the pathway determined by Kuchel et al [9]. The metabolites have their standard abbreviations.…”

“…In Figure 3 we see a reduced version of the pathway given by Kuchel et al [9]. Even in this simplified form, there remains a great deal of complexity.…”