Advantages and disadvantages of aggregating fluxes into synthetic and degradative fluxes when modelling metabolic pathways

It is now widely accepted that mathematical models are needed to predict th e behaviour of complex metabolic networks in the cell, in order to have a r ational basis for planning metabolic engineering with biotechnological or t herapeutical purposes. The great complexity of metabolic networks makes it crucial to simplify them for analysis, but without violating key principles of stoichiometry or thermodynamics. We show here, however, that models for branched complex systems are sometimes obtained that violate the stoichiom etry of fluxes at branch points and as a result give unrealistic metabolite concentrations at the steady state. This problem is especially important w hen models are constructed with the S-system form of biochemical systems th eory. However, the same violation of stoichiometry can occur in metabolic c ontrol analysis if control coefficients are assumed to be constant when try ing to predict the effects of large changes. We derive the appropriate matr ix equations to analyse this type of problem systematically and to assess i ts extent in any given model.