Strategies for representing metabolic pathways within biochemical systems theory: Reversible pathways (Q1123832)

There are two principal strategies for the generation of S-systems of reversible pathways (S-systems are the preferred representation in biochemical system theory): First, the ``reversible strategy'' that involves aggregation of incoming fluxes separately from outgoing fluxes for each metabolite to define a netflux that can be positive, negative or zero; secondly, the ``irreversible strategy'', that involves aggregation for forward and reverse fluxes through each reaction to define a net flux that is always positive. After a general description of the methodology and underlying theory a detailed analysis by means of a specific amphibolic pathway is carried out to compare both strategies. The main results are: (1) All S-system representations predict the same changes in concentrations for a given change in an independent concentration. (2) S-system representation based on reversible strategy is superior to that based on irreversible strategy according to accuracy in predicting steady state, accuracy in predicting transient responses, and robustness of representation. (3) Only reversible strategy yields a representation that is able to capture the principal characteristic of amphibolic pathways.