Metabolic Flux Analysis

In modern metabolomics, cellular reactions are observed as an integrated and networked system, termed as the metabolic network, instead of individual enzymatic reactions. Based on the metabolic network quantitated in terms of fluxes which are the rates at which materials are processed through the metabolic pathways, functional and regulatory activities of cells can be understood in its entirety. Typically, a realistic metabolic network which comprises catabolic and anabolic pathway fluxes of cells represents an underdetermined system from a stoichiometric viewpoint. This yields the intracellular fluxes that cannot be calculated from other fluxes measured. In order to determine those fluxes, 13 C labeling information is most frequently applied. This involves mathematical models that compute distributions of fluxes together with experimental tools for 13 C labeling analysis. In this regard, understating the modeling techniques that aim the metabolic flux analysis using 13 C isotopomer analysis is one central issue of metabolomics. Therefore, we describe the principle of different modeling strategies of the metabolic flux analysis in this chapter. First, we introduce the stoichiometry-based approach which is the foundation of the 13 C-based approaches. Further to this, the modeling aspect of 13 C-based approaches and related tools such as computer-aided optimal design of 13 C labeling experiments and numerical computation of fluxes from measured 13 C labeling states of metabolic products are treated. Also, the mathematical and statistical background is provided, which are relevant to the modeling of 13 C-based metabolic flux analysis.