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Metabolomics 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. Messenger ribonucleic acid ( mRNA) is a molecule of RNA encoding a chemical "blueprint" for a Protein product Gene expression is the process by which inheritable information from a Gene, such as the DNA sequence, is made into a functional Gene product, such Proteomics is the large-scale study of Proteins particularly their structures and functions. One of the challenges of systems biology is to integrate proteomic, transcriptomic, and metabolomic information to give a more complete picture of living organisms. Systems biology is a biology-based inter-disciplinary study field that focuses on the systematic study of complex interactions in biological systems, thus using a new perspective Proteomics is the large-scale study of Proteins particularly their structures and functions. The transcriptome is the set of all Messenger RNA (mRNA molecules or "transcripts" produced in one or a population of cells.

Contents

Metabolome

Metabolome 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. The transcriptome is the set of all Messenger RNA (mRNA molecules or "transcripts" produced in one or a population of cells. Proteomics is the large-scale study of Proteins particularly their structures and functions. 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. Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. The University of Alberta (U of A is a public research University located in Edmonton, Alberta, Canada. The University of Calgary is a research-intensive Public university in Calgary Alberta, Canada. They catalogued approximately 2500 metabolites, 1200 drugs and 3500 food components that can be found in the human body, as reported in the literature. Metabolomics is the "systematic study of the unique chemical fingerprints that specific cellular processes leave behind" - specifically the study of their small-molecule metabolite A drug, broadly speaking is any chemical substance that when absorbed into the body [3] This information, available at the Human Metabolome Database (HMDB is available at: www. hmdb. ca. ) and based on analysis of information available in the current the scientific literature, is far from complete. In contrast, much more is known about the metabolomes of other organisms, especially of plants, where over 50,000 metabolites have been characterized from the plant kingdom, and many thousands of metabolites have been identified and/or characterized from single plants. Metabolomics in today's world carries on its shoulders the huge responsibility of providing a detailed description of metabolic pathways and their workings, whether they be in humans, animals, or the plants we both eat and admire.

Metabolites

Metabolites are the intermediates and products of metabolism. Metabolism is the set of Chemical reactions that occur in living Organisms in order to maintain Life. The term metabolite is usually restricted to small molecules. In Chemistry, a molecule is defined as a sufficiently stable electrically neutral group of at least two Atoms in a definite arrangement held together by 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 are Organic compounds that are not directly involved in the normal growth, development or Reproduction of Organisms Ecology (from Greek grc οἶκος oikos, "house(hold" and grc -λογία -logia) is the scientific study of Examples include antibiotics and pigments. In modern usage an antibiotic is a Chemotherapeutic agent with activity against Microorganisms such as Bacteria, fungi or Protozoa For the drug referred to as "pigment" see Black tar heroin.

The metabolome forms a large network of metabolic reactions, where outputs from one enzymatic chemical reaction are inputs to other chemical reactions. Metabolomics is the "systematic study of the unique chemical fingerprints that specific cellular processes leave behind" - specifically the study of their small-molecule metabolite Metabolism is the set of Chemical reactions that occur in living Organisms in order to maintain Life. Enzymes are Biomolecules that catalyze ( ie increase the rates of Chemical reactions Almost all enzymes are Proteins A chemical reaction is a process that always results in the interconversion of Chemical substances The substance or substances initially involved in a chemical reaction are called Such systems have been described as hypercycles.

Metabonomics

Metabonomics is defined as "the quantitative measurement of the dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modification". This approach originated at Imperial College London and has been used in toxicology, disease diagnosis and a number of other fields. Imperial College London (officially The Imperial College of Science Technology and Medicine as given in its Royal Charter It is one of only three universities to have reached [4]

There has been some disagreement over the exact differences between 'metabolomics' and 'metabonomics', although 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. Nuclear magnetic resonance spectroscopy, most commonly known as NMR spectroscopy, is the name given to a technique which exploits the magnetic properties of certain nuclei Mass spectrometry is an analytical technique that identifies the chemical composition of a compound or sample based on the Mass-to-charge ratio of charged particles 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, regardless of species investigated, while 'metabonomics' is used to describe multiple (but not necessarily comprehensive) metabolic changes caused by a biological perturbation. The term 'metabonomics' is rarely used to describe research not directly related to human disease or nutrition. In practice, within the field of human disease research there is still a large degree of overlap in the way both terms are used, and they are often in effect synonymous.

History

Metabolic 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]

The development of metabolomics began 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. What sets metabolomics apart from strictly analytical chemistry-based analyses is the scope of the work. Three characteristics common to metabolomic research are:

  1. Effort is made to profile metabolites with as little bias as is possible towards a specific metabolite or group of metabolites. Nevertheless, all profiling approaches require extraction of metabolites from biological tissues, and will therefore be biased due to solvent properties. This holds true, but is reduced, even if multiple solvent systems are used.
  2. Large numbers of metabolites are profiled at the same time, instead of being analyzed one by one.
  3. Relationships between the metabolites are characterized, currently mostly by multivariate methods, although other data analysis tools are being developed.

The field of metabolomics exploded in the early 2000s, particularly as a result of efforts by researchers from the Max Planck Institute for Plant Physiology, in Golm, Germany, under the direction of Prof. Dr. Lothar Willmitzer. Their research, while still more appropriately called 'metabolite profiling' because they analyzed only hundreds of compounds and not the entire complement of the plant cell, set the framework for metabolomics-scale investigations. Their review articles promoting the field and its potential applications to agriculture, medicine, and other fields in the biological sciences, definitely had a strong stimulatory effect on the field as a whole.

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 a database of approximately 2500 metabolites, 1200 drugs and 3500 food components. Similar projects have been underway in several plant species, most notably Medicago truncatula and Arabidopsis thaliana for several years.

Analytical technologies

There are four important issues to be addressed for metabolite analysis: 1. Efficient and unbiased extraction of metabolites from biological tissues. 2. Separation of the analytes, usually by chromatography. Chromatography (from Greek χρώμα chroma, color and γραφειν"graphein" to write is the collective term for a family of Laboratory Electrophoresis, particularly capillary electrophoresis, is also used. 3. Detection of the analytes, following separation by chromatographic or other methods. 4. Identification and quantification of the analytes.

Separation methods

Detection methods

Key applications

See also

Sources and notes

  1. ^ B. This is a navigational and informational list. The terms 'Ome' and 'Omics' are derivations of the suffix -ome, which has been appended to a variety of previously existing Proteomics is the large-scale study of Proteins particularly their structures and functions. Cytomics is the study of cell systems (cytomes at a single cell level The term tumor metabolome describes the characteristic metabolic phenotype of Tumor cells Mass spectrometry is an analytical technique that identifies the chemical composition of a compound or sample based on the Mass-to-charge ratio of charged particles In Chemistry and Medicine, protein electrophoresis (aka Immunoelectrophoresis) is a method of analysing a mixture of Proteins by means Proteins are found in every cell and are essential to every biological process Protein structure is very complex determining a protein's structure involves first Swiss-Prot is a manually curated Biological database of Protein sequences Pfam is a large collection of Multiple sequence alignment and Hidden Markov models covering many common protein domains and families Bioinformatics is the application of information technology to the field of molecular biology Glycomics, an analogous term to Genomics and Proteomics, is the comprehensive study of Glycomes (the entire complement of Sugars whether free Lipidomics is the large-scale study of non-water-soluble Metabolites ( Lipids or Lipidome) For terminology see glossary below A DNA microarray is a High-throughput technology used in Molecular biology and in Systems biology is a biology-based inter-disciplinary study field that focuses on the systematic study of complex interactions in biological systems, thus using a new perspective Daviss, "Growing pains for metabolomics," The Scientist, 19[8]:25-28, April 25, 2005
  2. ^ First use of the term "metabolome" in the literature — Oliver, S. G. , Winson, M. K. , Kell, D. B. & Baganz, F. (1998). "Systematic functional analysis of the yeast genome". Trends Biotechnol. 16 (10): 373–378. Trends is a series of Scientific journals owned by Elsevier that publish review articles in a range of areas of Biology. PMID 9744112.  
  3. ^
    • First book on metabolomics — Harrigan, G. G. & Goodacre, R. (eds) (2003). RMetabolic Profiling: Its Role in Biomarker Discovery and Gene Function Analysis. Kluwer Academic Publishers (Boston). ISBN 1-4020-7370-4.  
    • Fiehn, O. , Kloska, S. & Altmann, T. (2001). "Integrated studies on plant biology using multiparallel techniques". Curr. Opin. Biotechnol. 12 (1): 82–86. Current Opinion is a series of review journals published by Elsevier on various subjects of biology PMID 11167078.  .
    • Fiehn, O. (2001). "Combining genomics, metabolome analysis, and biochemical modelling to understand metabolic networks. ". Comp. Funct. Genomics 2 (3): 155–168.   Publisher abstract link
    • Weckwerth, W. Metabolomics in systems biology. Annu. Rev. Plant Biol. 54, 669–689 (2003).
    • Goodacre, R. , Vaidyanathan, S. , Dunn, W. B. , Harrigan, G. G. & Kell, D. B. Metabolomics by numbers: acquiring and understanding global metabolite data. Trends Biotechnol. 22, 245–252 (2004).
    • Nicholson, J. K. , Holmes, E. , Lindon, J. C. & Wilson, I. D. The challenges of modeling mammalian biocomplexity. Nature Biotechnol. 22, 1268–1274 (2004). Stresses the role of intestinal microorganisms in contributing to the human metabolome.
    • van der Greef, J. , Stroobant, P. & van der Heijden, R. The role of analytical sciences in medical systems biology. Curr. Opin. Chem. Biol. 8, 559–565 (2004).
    • Kell, D. B. Metabolomics and systems biology: making sense of the soup. Curr. Opin. Microbiol. 7, 296–307 (2004).
    • Dunn, W. B. and Ellis, D. I. (2005) Metabolomics: current analytical platforms and methodologies. Trends in Analytical Chemistry 24(4), 285-294.
    • Ellis, D. I. and Goodacre, R. (2006) Metabolic fingerprinting in disease diagnosis: biomedical applications of infrared and Raman spectroscopy, Analyst, 131, 875-885. DOI:10. 1039/b602376m
    • Wishart, D. S. , Tzur, D. , Knox, C. , Eisner, R. , Guo, A. C. , Young, N. , Cheng, D. , Jewell, K. , Arndt, D. , Sawhney, S. , Fung, C. , Nikolai, L. , Lewis, M. , Coutouly, M. -A. , Forsythe, I. , Tang, P. , Shrivastava, S. , Jeroncic, K. , Stothard, P. , Amegbey, G. , Block, D. , Hau, D. D. , Wagner, J. , Miniaci, J. , Clements, M. , Gebremedhin, M. , Guo, N. , Zhang, Y. , Duggan, G. E. , Macinnis, G. D. , Weljie, A. M. , Dowlatabadi, R. , Bamforth, F. , Clive, D. , Greiner, R. , Li, L. , Marrie, T. , Sykes, B. D. , Vogel, H. J. , Querengesser, L. (2007) HMDB: The Human Metabolome Database. Nucleic Acids Research 35(Database issue), pp D521-6. Nucleic Acids Research or NAR is a Peer reviewed Scientific journal published by Oxford University Press. PMID: 17202168
  4. ^
    • Nicholson, J. K. , Lindon, J. C. , Holmes, E. (1999). “Metabonomics”: understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data. Xenobiotica. 11: p. 1181-1189.
    • Lindon, J. C. , Holmes, E. , Bollard, M. E. , Stanley, E. G. , and Nicholson, J. K. (2004) Metabonomics technologies and their applications in physiological monitoring, drug safety assessment and disease diagnosis. Biomarkers. Vol. 9, No. 1. p. 1-/31.
    • Brindle, J. T. , , Antti, H. , Holmes, E. , Tranter, G. , Nicholson, J. K. , Bethell, H. W. L. , Clarke, S. , Schofield, P. M. , McKilligan, E. , Mosedale, D. E. , & Grainger, D. J. (2002) Rapid and non-invasive diagnosis of the presence and severity of coronary heart disease using 1H NMR -based metabonomics. Nature Medicine. 8 (12): p. 1439-1444.
    • Bollard, M. E. , Stanley, E. G. , Lindon, J. C. , Nicholson, J. K. , & Holmes, E. (2005) NMR-based metabonomic approaches for evaluating physiological influences on biofluid composition. NMR Biomed. 2005: p. 18:143–162.
  5. ^ Preti, George. "Metabolomics comes of age?" The Scientist, 19[11]:8, June 6, 2005.
  6. ^ The European Nutrigenomics Network

PMID: 17202168

http://lab.bcb.iastate.edu/projects/plantmetabolomics/

External links

Genomics topics
Genome project | Paleopolyploidy | Glycomics | Human Genome Project | Proteomics | Metabolomics
Chemogenomics | Structural genomics | Pharmacogenetics | Pharmacogenomics | Toxicogenomics | Computational genomics
Bioinformatics | Cheminformatics | Systems biology
Genomics is the study of an organism's entire Genome. The field includes intensive efforts to determine the entire DNA sequence of organisms and fine-scale Genetic Genome projects are Scientific endeavours that ultimately aim to determine the complete Genome sequence of an Organism (be it an Animal, a Paleopolyploidy refers to ancient Genome duplications which occurred at least several million years ago (mya Glycomics, an analogous term to Genomics and Proteomics, is the comprehensive study of Glycomes (the entire complement of Sugars whether free The Human Genome Project (HGP was an international Scientific research project with a primary goal to determine the sequence of chemical base pairs which make up DNA Proteomics is the large-scale study of Proteins particularly their structures and functions. Chemogenomics can be defined as the study of genomic responses to Chemical compounds The goal is the rapid identification of novel Drugs and Drug targets Structural genomics consists in the determination of the three dimensional structure of all Proteins of a given organism by experimental methods such as X-ray crystallography The terms Pharmacogenomics and pharmacogenetics tend to be used interchangeably and a precise consensus definition of either remains elusive Pharmacogenomics is the branch of Pharmacology which deals with the influence of genetic variation on drug response in patients by correlating Gene expression Toxicogenomics is a field of Science that deals with the collection interpretation and storage of information about gene and Protein activity within Computational genomics is the study of deciphering biology from Genome sequences using computational analysis Bioinformatics is the application of information technology to the field of molecular biology Cheminformatics (also known as chemoinformatics and chemical informatics) is the use of computer and informational techniques applied to a range of problems Systems biology is a biology-based inter-disciplinary study field that focuses on the systematic study of complex interactions in biological systems, thus using a new perspective

Dictionary

metabolomics

-noun

  1. (biochemistry) The study of the range of metabolites present in a person's body at normal times, and when suffering from specific diseases; may be useful as a diagnostic tool
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