Comprehensive Metabolic Analysis for Understanding of Disease

Comprehensive measurement of intermediary metabolites and changes in metabolic activity lead to the improved detection and understanding of diseases. Metabolomics is increasingly getting integrated with genomic and transcriptomic profiling methods. This chapter describes current methodologies for metabolic profiling and flux analysis and discusses the instrumentation for measurement of large groups of intermediary metabolites as well as computational methods for analyzing such data. Instrumentation for measurement of large groups of intermediary metabolites as well as computational methods for analyzing such data are emerging. This surge in development of metabolomics technologies confers a number of potential advantages for disease research. Human beings contain approximately 5000 discrete small molecule metabolites, far less than the estimate of 25,000 genes and 100,000 proteins. This makes metabolomics the most tractable of the "omics" sciences. It also measures changes in metabolic or chemical milieu that are downstream of genomic and proteomic alterations, potentially providing the most integrated picture of biological status. Further, the identification of metabolic fingerprints for specific diseases has practical utility for development of therapies because metabolic changes immediately suggest enzymatic drug targets. Thus, metabolomics is likely to be a powerful and precise tool for discerning mechanisms of action and possible toxicological effects of drug therapies. © 2010