Understanding metabolism with flux analysis: From theory to application

Quantitative and qualitative knowledge of metabolic rates (i.e. fluxes) over a metabolic network and in specific cellular compartments gives insights into the regulation of metabolism and helps to understand the contribution of metabolic alterations to pathology. In this review we introduce methodology to resolve metabolic fluxes from stable isotope labeling and relevant techniques in model development, model simplification, flux uncertainty analysis and experimental design that together is termed metabolic flux analysis. Finally we discuss applications using metabolic flux analysis to elucidate mechanisms pertinent to tumor cell metabolism. We hope that this review gives the readers a brief introduction of how flux analysis is conducted, how technical issues related to it are addressed, and how its application has contributed to our knowledge of tumor cell metabolism.