Metabolism is one of the most complex cellular processes. Connections between biochemical reactions via substrate and product metabolites create complex metabolic networks that may be analyzed using network theory, stoichiometric analysis, and information on protein structure/function and metabolite properties. These frameworks take into consideration different aspects of enzyme chemistry, enzyme structure and metabolite structure, and demonstrate the impact of metabolic biochemistry on the systemic properties of metabolism. The integration of these approaches and the systematic classification of enzyme function and the chemical structure of metabolites will enhance our understanding of metabolism, and could improve our ability to predict enzyme function and novel metabolic pathways.