Metabolome defined

While the clinical use of MS/MS of hormonal steroids is new, metabolite analysis by gas chromatography (GC)-mass spectrometry (MS) has been available for 40 years, since few immunoassays were developed for urinary analytes. Profile analysis is a very powerful technique and it must be recognized that with few exceptions, all disorders of steroid synthesis and metabolism first had their metabolome defined... 

Several biochemical events occur posttranscriptionally that define the response of cells to stimuli. For instance, alternative splicing, posttrans-lational modifications, regulation of enzyme activities, distribution of metabolites between cellular compartments, necessitate analysis at the level of the proteome and the metabolome. 

Characterizing the metabolome is only one component which needs to be integrated with its counterparts to realize its potential contributions to drug discovery and development. When all of the work has been done to define the universe of the transcriptome, proteome, and metabolome, and biomarker sets have been identified, 90% of the work remains in the validation and acceptance of these patterns. 

There are other small biomolecules, specific to certain types of cells or organisms. For example, vascular plants contain, in addition to the universal set, small molecules called secondary metabolites, which play a role specific to plant life. These metabolites include compounds that give plants their characteristic scents, and compounds such as morphine, quinine, nicotine, and caffeine that are valued for their physiological effects on humans but used for other purposes by plants. The entire collection of small molecules in a given cell has been called that cell s metabolome, in parallel with the term genome (defined earlier and expanded on in... 

However, it is clear that the ease of collecting proteome data currently exceeds the capacity to analyse it. Therefore, international standards are being sought for proteomic experiments, such as the proteomics standards initiative (PSI, http //psidev.source forge.net/), and the proteomics experiment data repository (PEDRo, http //pedro.man.ac.uk). The aim is to provide proteomic researchers with the opportunity to query and reproduce protocols, analyse raw or metadata from other laboratories, and to link the proteome with the respective transcriptome and the metabolome. The Human Proteome Organization (HUPO) is establishing a defined infrastructure for human data submission, and annotation for the numerous proteomic data platforms. This will also be required to effectively develop parasitic flatworm proteomics. 

In what many consider to be a landmark publication on metabolomics, Fiehn et al. (2000) state it is crucial to perform unbiased (metabolite) analyses in order to define precisely the biochemical function of plant metabolism. The authors argue that for metabolomics/metabolite profiling to become a robust and sensitive method suited to automation, a mature technology such as gas chromatography-mass spectrometry (GC-MS) is required as an analytical technique. The authors go on to describe a simple sample preparation and analysis regime that allowed for the detection and quantification of more than 300 compounds from a single-leaf sample extract. 

Metabolomics as defined in Section 5.1.1 is a recent addition to accepted technology platforms. As such, when researching this chapter, it became obvious that there is... 

Ippolito JE, Xu J, Jain S, et al. An integrated functional genomics and metabolomics approach for defining poor prognosis in human neuroendocrine cancers. Proc Natl AcadSci USA. 2005 102(28) 9901-9906. 

Metabolism is considered to be a phenotype. It integrates all the factors from nutrition to environment to genetics assessing one s current state of health. Metabolomics arose from metabolic control theory and was originally based on the metabolome, which is defined as the metabolic composition of a cell and is analogous to the genome or proteome. In metabonomics, static cellular and biofluid concentrations of endogenous metabolites are evaluated over a time-course. 

NMR spectroscopy evolved primarily as a tool for the characterization of pure compounds or simple well-defined mixtures (see Section 9.06.1.2), whereas strategies for the NMR spectroscopic identification of compounds from complex mixtures have been developed only recently. As several examples have shown, using NMR spectroscopy for the analysis of complex mixtures can open up new perspectives and may enable new lines of inquiry in both natural products chemistry and metabolomics. Before discussing some of these examples in greater detail, it is useful to consider what developments spawned the recent surge in applications of NMR spectroscopy to mixtures and what prevented earlier uses of NMR spectroscopy for this purpose. 

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