Metabolic network sensitivity analysis

A linear sensitivity analysis of metabolic regulation in nonsteady states is described. This treatment considers the effects of enzymatic and nonenzymatic reactions and spontaneous rapid equilibria. Sensitivity coefficients summarizing the influence of metabolite concentrations on reaction rates and pathway net flux are defined, as are sensitivity coefficients summarizing the effects of enzymes on metabolite concentrations and net flux. The sensitivity analysis is implemented in an easily used set of computer programs. A four-enzyme test model was shown to be resistant to intuitive interpretation. Sensitivity analysis showed a shift of control from the end of the enzymic sequence to the beginning of the sequence with changing metabolic state. The homeostatic behavior of the test system was shown to depend on the nonenzymatic reactions as well as on the enzymes. Under certain conditions metabolic regulation is shared so intimately among enzymes and spontaneous reactions that separation of their effects is impossible.