An integrated metabolic pathway analysis based on metabolic signal flow diagram and cellular energetics for Saccharomyces cerevisiae

Noting that a metabolic signal flow diagram-based modelling approach developed by Endo and Inoue (Endo and Inoue, 1976) is restricted to a linear system applicable over the range of linearity of interest, we attempted to overcome such a restriction, and developed an integrated modelling approach by incorporating an energetic model into MSFD. The proposed approach was applied to continuous cultivation of Saccharomyces cerevisiae. The problem was formulated in terms of a flow network that has as its objective maximal ATP synthesis. The metabolic conversion coefficients C_ij in the metabolic signal flow diagram can be expressed as a function of z, the fraction of the total carbon flux into the Embden-Meyerhof-Parnas pathway. The resulting model equations were used for analysis of the directions of carbon fluxes and the degree of activation of a particular pathway or reaction loop in S. cerevisiae cultivation, in which the physiological state and the changes in fluxes of the main metabolic pathways in the viable cells can be distinguished in terms of the signs of the metabolic coefficients.