understanding regulation of metabolism through feasibility analysis通过可行性分析理解调节新陈代谢.pdf

Understanding Regulation of Metabolism through Feasibility Analysis 1,3,4 2,3,4,5 1 2,3,4,5 1,3,4 Emrah Nikerel *, Jan Berkhout , Fengyuan Hu , Bas Teusink , Marcel J. T. Reinders , Dick de Ridder1,3,4 1The Delft Bioinformatics Lab, Department of Intelligent Systems, Delft University of Technology, Delft, The Netherlands, 2 Systems Bioinformatics IBIVU, Faculty of Earth and Life Sciences, Vrije Universiteit, Amsterdam, The Netherlands, 3 Kluyver Centre for Genomics of Industrial Fermentation, Delft, The Netherlands, 4 Netherlands Consortium for Systems Biology (NCSB), Amsterdam, The Netherlands, 5 Netherlands Institute Systems Biology (NISB), Amsterdam, The Netherlands Abstract Understanding cellular regulation of metabolism is a major challenge in systems biology. Thus far, the main assumption was that enzyme levels are key regulators in metabolic networks. However, regulation analysis recently showed that metabolism is rarely controlled via enzyme levels only, but through non-obvious combinations of hierarchical (gene and enzyme levels) and metabolic regulation (mass action and allosteric interaction). Quantitative analyses relating changes in metabolic fluxes to changes in transcript or protein levels have revealed a remarkable lack of understanding of the regulation of these networks. We study metabolic regulation via feasibility analysis (FA). Inspired by the constraint-based approach of Flux Balance Analysis, FA incorporates a model describing kinetic interactions between molecules. We enlarge the portfolio of objectives for the cell by defining three main physiologically relevant objectives for the cell: function, robustness and