Metabolomics and fluxomics approaches.

Systems biology is based on the understanding that the behaviour of the whole is greater than would be expected from the sum of its parts. Thus the ultimate goal of systems biology is to predict the behaviour of the whole system on the basis of the list of components involved. Recent advances in '-omics' technologies and the development of new computational techniques and algorithms have greatly contributed to progress in this field of biology. Among the main '-omics' technologies, metabolomics is expected to play a significant role in bridging the phenotype-genotype gap, since it amplifies changes in the proteome and provides a better representation of the phenotype of an organism than other methods. However, knowledge of the complete set of metabolites is not enough to predict the phenotype, especially for higher cells in which the distinct metabolic processes involved in their production and degradation are finely regulated and interconnected. In these cases, quantitative knowledge of intracellular fluxes is required for a comprehensive characterization of metabolic networks and their functional operation. These intracellular fluxes cannot be detected directly, but can be estimated through interpretation of stable isotope patterns in metabolites. Moreover, analysis of these fluxes by means of metabolic control theories offers a potentially unifying, holistic paradigm to explain the regulation of cell metabolism. In this chapter, we provide an overview of metabolomics and fluxomics, highlighting stable isotope strategies for fluxome characterization. We also discuss some of the tools used to quantitatively analyse the control exerted by components of the network over both the metabolome and the fluxome. Finally, we outline the role and future of metabolomics and fluxomics in drug discovery.