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MetabolomicsMetabolomics is the "systematic study of the unique chemical fingerprints that specific cellular processes leave behind" - specifically, the study of their small-molecule metabolite profiles.[1] The metabolome represents the collection of all metabolites in a biological organism, which are the end products of its gene expression. Thus, while mRNA gene expression data and proteomic analyses do not tell the whole story of what might be happening in a cell, metabolic profiling can give an instantaneous snapshot of the physiology of that cell. One of the challenges of systems biology is to integrate proteomic, transcriptomic, and metabolomic information to give a more complete picture of living organisms. Additional recommended knowledge
MetabolomeMetabolome refers to 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.[2] The word was coined in analogy with transcriptomics and proteomics; like the transcriptome and the proteome, the metabolome is dynamic, changing from second to second. Although the metabolome can be defined readily enough, it is not currently possible to analyse the entire range of metabolites by a single analytical method. In January 2007, scientists at the University of Alberta and the University of Calgary completed the first draft of the human metabolome. They have catalogued and characterized 2500 metabolites, 1200 drugs and 3500 food components that can be found in the human body.[3] Metabolomics in today's world carries on its shoulders the huge responsibility of providing a detailed description of human pathways and their workings. MetabolitesMetabolites are the intermediates and products of metabolism. The term metabolite is usually restricted to small molecules. 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. Examples include antibiotics and pigments. The metabolome forms a large network of metabolic reactions, where outputs from one enzymatic chemical reaction are inputs to other chemical reactions. Such systems have been described as hypercycles. MetabonomicsMetabonomics is defined as "the quantitative measurement of the dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modification". This approach originated in Imperial College London and has been used in toxicology, disease diagnosis and a number of other fields.[4] There is some disagreement over the exact differences between 'metabolomics' and 'metabonomics'; in general, the term 'metabolomics' is more commonly used. The difference between the two terms is not related to choice of analytical platform: although metabonomics is more associated with NMR spectroscopy and metabolomics with mass spectrometry-based techniques, this is simply because of usages amongst different groups that have popularized the different terms. While there is still no absolute agreement, there is a growing consensus that the difference resides in the fact that 'metabolomics' places a greater emphasis on comprehensive metabolic profiling, while 'metabonomics' is used to describe multiple (but not necessarily comprehensive) metabolic changes caused by a biological perturbation. In practice, there is still a large degree of overlap in the way the terms are used, and they are often in effect synonymous. HistoryMetabolic biochemists have arguably been 'doing metabolomics' for decades. The chromatographic separation techniques that made the initial detection of metabolites possible were developed in the late 1960's, which marks the technical origin of the field. [5] Metabolomics began develop in 1970 by Arthur Robinson investigating Pauling's ideas as to whether biological variability could be explained on the basis of far wider ranges of nutritional requirements than what was generally recognized. In analyzing the "messy" chromatographic patterns of urine from vitamin B6-loaded subjects, Robinson realized that the patterns of hundreds or thousands of chemical constituents in urine contained much useful information. Although it was not called metabolomics, the first paper devoted to this topic was titled, “Quantitative Analysis of Urine Vapor and Breath by Gas-Liquid Partition Chromatography”, by Robinson and Pauling in 1971 and published in the Proceedings of the National Academy of Sciences. Since then, Robinson has had nineteen more papers published on the quantitative patterns of metabolites in body fluids (see below). Robinson and colleagues have identified several diseases, conditions, and physiological age based on this data. It was his expectation that body fluid analysis can be optimized to make a low cost, information-rich, medically-relevant means of measuring metabolically-driven changes in functional state, even when the chemical constituents are all in the “normal range”. The core idea that Robinson conceived is that information-rich data that reflects the functional status of a complex biological system resides in the quantitative and qualitative pattern of metabolites in body fluids. Twenty years later, others began to realize the value of this approach, and interest in this has mushroomed. The name metabolomics was coined in the 1990s (the first paper using the word metabolome is Oliver, S. G., Winson, M. K., Kell, D. B. & Baganz, F. (1998). Systematic functional analysis of the yeast genome. Trends Biotechnol. 16, 373-378), and in 2004 a society was formed to promote its study. Many of the bioanalytical methods used for metabolomics have been adapted (or in some cases simply adopted) from existing biochemical techniques. Two characteristics common to metabolomic research are:
On January 23rd, 2007, the Human Metabolome Project, led by Dr. David Wishart of the University of Alberta, Canada, completed the first draft of the human metabolome, consisting of 2500 metabolites, 1200 drugs and 3500 food components. Analytical technologies: separation methodsThere are two issues to be addressed for metabolite analysis: 1. separation of the analytes, usually by chromatography. Electrophoresis, particularly capillary electrophoresis, is also used. 2. Detection of the analytes, following separation by chromatographic or other methods.
Analytical technologies: detection methods
Key applications
See also
References
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- The Human Serum Metabolome Project (HUSERMET)
- BMRB - Free NMR spectral database of common metabolites
- MMCD - Free Bioinformatics resources for NMR and MS-based metabolomics
- Metabolomics, a peer-reviewed journal
- Metabolic Profiling Forum - The Industry Forum for Metabolomics Research and Application
- Metabolomics Society
- Metabolomics Lab Keio university
- Metabolite Profiling in Plant Science in MPI-MP, Golm
- Metabolomics Science
- Metabolomic Analysis at the University of California Davis
- Metabolite Link Database (Metlin)
- The European Nutrigenomics Network
- The Human Metabolome Project
- The Human Metabolome Database
- The Human Metabolome Library
- Metabolomics at ISAS - Institute for Analytical Sciences
- The Magnetic Resonance Metabolomics Database of Linkoping (MDL) - contains NMR data of many small metabolites
- Proteome.org
- Bioinformatics Journal
- PDF of Reporting Standards for Metabolomic Studies
- Scientists complete human metabalome
- Metabolomics, IBT1&2, Forschungszentrum Jülich, Germany
Categories: Metabolism | Systems biology | Bioinformatics | Genomics