Metabonomics and Metabolomics
The vast information revealed with the sequencing of the human genome has yet to produce the advances in personalized medicine expected. However, the tech-niques and processes of identifying clinically signifi-cant biomarkers of human disease and drug safety have fostered the systematic study of the unique chemical fingerprints that specific cellular processes leave behind, specifically, their small-molecule meta-bolite profiles (Nicholson and Wilson, 2003; Fernie et al., 2004; Delnomdedieu and Schneider, 2005; Lindon et al., 2005; Weckwerth and Morgenthal, 2005) The human “metabolome” represents the collection of all metabolites in a biological organism, which are the end products of its gene expression and gene product function. Thus, while genomics and proteomics do not tell the whole story of what might be happening within a cell, metabolic profiling can give an instantaneous snapshot of the physiology of that cell.
High performance liquid chromatography coupled with sophisticated NMR and mass spectrometry (MS) techniques are used to separate and quantify complex metabolite mixtures found in biological fluids to get a picture of the metabolic continuum of an organism influenced by an internal and external environment. The field of metabonomics is the holistic study of the metabolic continuum at the equivalent level to the study of genomics and proteomics. However, unlike genomics and proteomics, microarray technology is little used since the molecules assayed in metabonomics are small molecule end products of gene expression and resulting protein function. The term metabolomics has arisen as the metabolic composition of a cell at a specified time whereas metabonomics includes both the static metabolite composition and concentrations as well as the full time course fluctuations. Coupling the information being collected in biobanks, large collections of patient’s biological samples and medical records, with metabonomic and metabolomic studies will not only detect why a given metabolite level is increasing or decreasing, but may reliably predict the onset of disease. Also, the techniques are finding use in drug safety screening, identification of clinical biomarkers, and systems biology studies (see below).