Comparative characterization of the fermentation pathway of Saccharomyces cerevisiae using biochemical systems theory and metabolic control analysis: Model definition and nomenclature

Abstract

Mathematical tools that involve the determination of systemic responses to small changes in metabolites or enzymes have demonstrated their utility for analyzing metabolic pathways. The different methodologies based on these ideas allow for modeling and analyzing biochemical pathways focusing on the coordinate behavior of the whole system. However, one must become familiar with the difference in nomenclature and methodology to relate the models and results obtained by applying these techniques and to appreciate their potential for answering fundamental questions about biochemical systems. In the following three papers we show how this can be facilitated by comparing the nomenclature, methodology, and results of the two leading techniques in this area, metabolic control analysis and biochemical systems theory, using a model of the fermentation pathway in Saccharomyces cerevisiae as a reference system. In the present paper we review the nomenclature, technical concepts, and related experimental measurements while creating a practical dictionary for the reference system that makes the relatedness of the two approaches more apparent. In the second paper, subtitled Steady-State Analysis, we show that both approaches give the same picture for many systemic responses of the reference system. In the third paper of this series, subtitled Model Validation and Dynamic Behavior, we show that the quality of the model can be assessed by studying the sensitivity to changes in the system parameters. We hope to illustrate the usefulness of these tools in providing an interpretation of the experimental measurements in a specific metabolic pathway.