Identification of flux control in metabolic networks using non-equilibrium thermodynamics

作者：Bordel Sergio; Nielsen Jens^*

来源：Metabolic Engineering, 2010, 12(4): 369-377.

DOI：10.1016/j.ymben.2010.03.001

• Thermodynamics
• Metabolic fluxes
• Elementary flux modes
• Regulation
• Constraining reactions

A method is presented to identify flux controlling reactions in metabolic networks using experimentally determined flux distributions. The method is based on the application of Ziegler's principle for the maximization of entropy production. According to this principle a metabolic network tends to maximize the entropy production rate while satisfying mass balances and maximal rate constraints. Experimental flux data corresponding to four different metabolic states of Saccharomyces cerevisiae were used to identify the corresponding flux controlling reactions. The bottleneck nature of several of the identified reactions was confirmed by earlier studies on over-expression of the identified target genes. The method also explains the failure of all the previous trials of increasing the glycolysis rate by direct over-expression of several glycolytic enzymes. These findings point to a wi

• 出版日期2010-7