Sensitivity analysis for the reduction of complex metabolism models

Two different model reduction strategies are studied in order to test their applicability to reduce complex metabolism models. Using a model of one pre-identified model set describing complex metabolic dynamics after glucose pulse stimulation, a model reduction method based on the parameter tuning importance is compared with a pea based approach. Up to 49 of 122 parameters are rejected without significant changes of the simulated trajectories and of the flux distribution. Applying the reduction procedure to 12 other dynamic models reveals a general model structure inconsistency within the description of the pentose phosphate pathway. That points out the need of additional experiments to reproduce metabolite courses especially of this metabolic pathway. Thus the sensitivity based model reduction procedure is qualified as a promising tool for the model structure check and can be very useful for the entire model validation process which also includes the critical analysis of the data sets underlying the models. (C) 2004 Elsevier Ltd. All rights reserved.