Metabolic modeling intermediate approaches

Specifically, SKM seeks to overcome several known deficiencies of stoichiometric analysis While stoichiometric analysis has proven immensely effective to address the functional capabilities of large metabolic networks, it fails for the most part to incorporate dynamic aspects into the description of the system. As one of its most profound shortcomings, the steady-state balance equation allows no conclusions about the stability or possible instability of a metabolic state, see also the brief discussion in Section V.C. The objectives and main requirements in devising an intermediate approach to metabolic modeling are as follows, a schematic summary is depicted in Fig. 25 ... 

In this section, we describe a recently proposed approach that aims overcome some of the difficulties [23, 84, 296, 325] Structural Kinetic Modeling (SKM) seeks to provide a bridge between stoichiometric analysis and explicit kinetic models of metabolism and represents an intermediate step on the way from topological analysis to detailed kinetic models of metabolic pathways. Different from approximative kinetics described above, SKM is based on those properties that are a priori independent of the functional form of the rate equation. 

The development of kinetic schemes for sequences of enzyme reactions contributes to the resolution of two problems. The first of these, the more complex one, concerns the study of the control of metabolic pathways and has been of major interest to biochemists for some time. Two related approaches to the problem have been developed for the interpretation of the behaviour of large assemblies of coupled enzyme reactions. Models can be made which contain the differential equations for the progress of the reactions for all the enzymes of a system. The numerical solutions of this set of equations can be compared with the experimental data for the concentrations of intermediates and their rates of change. Iterative improvements of the model can then be made. Alternatively, if data are only available for a... 

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