PubMed1984
As a starting point for modeling of metabolic networks this paper considers the simple Michaelis-Menten reaction mechanism. After the elimination of diffusional effects a mathematically intractable mass action kinetic model is obtained. The properties of this model are explored via scaling and linearization. The scaling is carried out such that kinetic properties, concentration parameters and external influences are clearly separated. We then try to obtain reasonable estimates for values of the dimensionless groups and examine the dynamic properties of the model over this part of the parameter space. Linear analysis is found to give excellent insight into reaction dynamics and it also gives a forum for understanding and justifying the two commonly used quasi-stationary and quasi-equilibrium analyses. The first finding is that there are two separate time scales inherent in the model existing over most of the parameter space, and in particular over the regions of importance here. Full modal analysis gives a new interpretation of quasi-stationary analysis, and its extension via singular perturbation theory, and a rationalization of the quasi-equilibrium approximation. The new interpretation of the quasi-steady state assumption is that the applicability is intimately related to dynamic interactions between the concentration variables rather than the traditional notion that a quasi-stationary state is reached, after a short transient period, where the rates of formation and decomposition of the enzyme intermediate are approximately equal. The modal analysis reveals that the generally used criterion for the applicability of quasi-stationary analysis that total enzyme concentration must be much less than total substrate concentration, et much less than St, is incomplete and that the criterion et much less than Km much less than St (Km is the well known Michaelis constant) is the appropriate one. The first inequality (et much less than Km) guarantees agreement over the longer time scale leading to quasi-stationary behavior or the applicability of the zeroth order outer singular perturbation solution but the second half of the criterion (Km much less than St) justifies zeroth order inner singular perturbation solution where the substrate concentration is assumed to be invariant. Furthermore linear analysis shows that when a fast mode representing the binding of substrate to the enzyme is fast it can be relaxed leading to the quasi-equilibrium assumption. The influence of the dimensionless groups is ascertained by integrating the equations numerically, and the predictions made by the linear analysis are found to be accurate.(ABSTRACT TRUNCATED AT 400 WORDS)