CONTROL ANALYSIS OF METABOLIC SYSTEMS INVOLVING QUASI-EQUILIBRIUM REACTIONS

Reactions for which the rates are extremely sensitive to changes in th e concentrations of variable metabolite concentrations contribute litt le to the control of biochemical reaction networks, Yet they do interf ere with the calculation of the system's behaviour, both in terms of n umerical integration of the rate equations and in terms of the analysi s of metabolic control, We here present a way to solve this problem sy stematically for systems with time hierarchies. We identify the fast r eactions and fast metabolites, group them apart from the other (''slow '') reactions and metabolites, and then apply the appropriate quasi-eq uilibrium condition for the fast subsystem, This then makes it possibl e to eliminate the fast reactions and their elasticity coefficients fr om the calculations, allowing the calculation of the control coefficie nts of the slow reactions in terms of the elasticity coefficients of t he slow reactions, As expected, the elasticity coefficients of the fas t reactions drop out of the calculations, and they are irrelevant for control at the time resolution of the steady state of the slow reactio ns, The analysis, when applied iteratively, is expected to be particul arly valuable for the control analysis of living cells, where a time h ierarchy exists, the fastest being at the level of enzyme kinetics and the slowest at gene expression. (C) 1998 Elsevier Science B.V.