Moselio Schaechter

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May 21, 2009

Of Terms in Biology: Metabolomics and Metabonomics

by Merry


Schematic of the 'omic hierarchy: genomics,
transcriptomics, proteomics, and metabolomics.
(Yes, the figure leaves out a few others, e.g.,
epigenomics and phenomics.) Source.

What is metabolomics? Oh, that's easy. It's the study of the metabolome. Very good. Now, what is the metabolome?

  • the collection of all metabolites in a biological organism, which are the end products of its gene expression. (Source)
  • the complete set of small-molecule metabolites (such as metabolic intermediates, hormones and other signalling molecules, and secondary metabolites) to be found within a biological sample, such as a single organism. (Source)

Ergo, metabolomics is the study of the complete collection of metabolites present in a cell or tissue under a particular set of conditions (= the metabolome) generating a biochemical profile. (Source) It's 'omics for the small molecules.

There is a similar term, metabonomics, that differs more in practice than in definition. It is usually applied only to studies of human nutrition and responses to drugs or disease, and usually compares profiles without identifying individual compounds.

The technology employed here is sophisticated and impressive: NMR spectroscopy and mass spectrometry (MS) for the detection and analysis of metabolites. NMR excels in determining the structure of unknown compounds. MS, on the other hand, offers high sensitivity and high throughput, and when coupled with a preliminary separation step, such as gas chromatography, can resolve very complex biological samples.

But the biological systems to be observed lack such cold precision. Sample preparation is the most time-consuming and most important step. Metabolites are fast moving targets. For S. cerevisiae growing aerobically on glucose, the typical half-life for an intracellular metabolite is on the order of a second or less. (Source) Thus the first step is the rapid quenching of all biochemical processes.

Then there is the goal of extracting the maximum number of metabolites with minimum losses and alteration. Unlike the proteome, for example, the metabolome consists of extremely diverse chemical compounds from ionic inorganic species to hydrophilic carbohydrates, volatile alcohols and ketones, amino and non-amino organic acids, hydrophobic lipids, and complex natural products. That complexity makes it virtually impossible to simultaneously determine the complete metabolome. (Source) What to do? You can use several different extraction and analysis procedures and combine the results. Sometimes focusing on one method may be adequate, still giving you data on a large number of metabolites.

Lastly, there is the analysis of the massive amounts of data obtained. The "stare and compare" method is inadequate. Relationships between the metabolites can be characterized, currently mostly by multivariate analysis, although other tools are being developed.

Why do we need it? To bridge the gap between phenotype and the other 'omes. The level of the metabolites are determined by the concentration and the properties of the enzymes, and their level is, therefore, a complex function of many different regulatory processes inside the cell; i.e., regulation of transcription and translation, regulation of protein–protein interactions, and allosteric regulation of enzymes through their interaction with metabolites. Thus, the level of metabolites represents integrative information of the cellular function, and, hence, defines the phenotype of a cell or tissue in response to genetic or environmental changes. (Source)

It also has been used in less grand ways, e.g., to monitor effects of a herbicide on plants, to identify the responses of a host to infection, and for taxonomic classification of fungi based on secondary metabolites. It can contribute to gene annotation by pinpointing the metabolites altered by mutations.

It may even tell us whether or not an organically grown apple really is different.


good introduction

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