The metabolome refers to the complete set of small-molecule chemicals found within a biological sample. The biological sample can be a cell, a cellular organelle, an organ, a tissue, a tissue extract, a biofluid or an entire organism. The small molecule chemicals found in a given metabolome may include both endogenous metabolites that are naturally produced by an organism (such as amino acids, organic acids, nucleic acids, fatty acids, amines, sugars, vitamins, co-factors, pigments, antibiotics, etc.) as well as exogenous chemicals (such as drugs, environmental contaminants, food additives, toxins and other xenobiotics) that are not naturally produced by an organism.
In other words, there is both an endogenous metabolome and an exogenous metabolome. The endogenous metabolome can be further subdivided to include a "primary" and a "secondary" metabolome (particularly when referring to plant or microbial metabolomes). A primary metabolite is directly involved in the normal growth, development, and reproduction. A secondary metabolite is not directly involved in those processes, but usually has important ecological function. Secondary metabolites may include pigments, antibiotics or waste products derived from partially metabolized xenobiotics. The study of the metabolome is called metabolomics.
Origins
The word metabolome appears to be a blending of the words "metabolite" and "chromosome". It was constructed to imply that metabolites are indirectly encoded by genes or act on genes and gene products. The term "metabolome" was first used in 1998 and was likely coined to match with existing biological terms referring to the complete set of genes (the genome), the complete set of proteins (the proteome) and the complete set of transcripts (the transcriptome). The first book on metabolomics was published in 2003. The first journal dedicated to metabolomics (titled simply "Metabolomics") was launched in 2005 and is currently edited by Prof. Roy Goodacre. Some of the more significant early papers on metabolome analysis are listed in the references below.
Measuring the metabolome
The metabolome reflects the interaction between an organism's genome and its environment. As a result, an organism's metabolome can serve as an excellent probe of its phenotype (i.e. the product of its genotype and its environment). Metabolites can be measured (identified, quantified or classified) using a number of different technologies including NMR spectroscopy and mass spectrometry. Most mass spectrometry (MS) methods must be coupled to various forms of liquid chromatography (LC), gas chromatography (GC) or capillary electrophoresis (CE) to facilitate compound separation. Each method is typically able to identify or characterize 50-5,000 different metabolites or metabolite "features" at a time, depending on the instrument or protocol being used. Currently it is not possible to analyze the entire range of metabolites by a single analytical method.
Nuclear magnetic resonance (NMR) spectroscopy is an analytical chemistry technique that measures the absorption of radiofrequency radiation of specific nuclei when molecules containing those nuclei are placed in strong magnetic fields. The frequency (i.e. the chemical shift) at which a given atom or nucleus absorbs is highly dependent on the chemical environment (bonding, chemical structure nearest neighbours, solvent) of that atom in a given molecule. The NMR absorption patterns produce "resonance" peaks at different frequencies or different chemical shifts – this collection of peaks is called an NMR spectrum. Because each chemical compound has a different chemical structure, each compound will have a unique (or almost unique) NMR spectrum. As a result, NMR is particularly useful for the characterization, identification and quantification of small molecules, such as metabolites. The widespread use of NMR for "classical" metabolic studies, along with its exceptional capacity to handle complex metabolite mixtures is likely the reason why NMR was one of the first technologies to be widely adopted for routine metabolome measurements. As an analytical technique, NMR is non-destructive, non-biased, easily quantifiable, requires little or no separation, permits the identification of novel compounds and it needs no chemical derivatization. NMR is particularly amenable to detecting compounds that are less tractable to LC-MS analysis, such as sugars, amines or volatile liquids or GC-MS analysis, such as large molecules (>500 Da) or relatively non-reactive compounds. NMR is not a very sensitive technique with a lower limit of detection of about 5 μM. Typically 50-150 compounds can be identified by NMR-based metabolomic studies.