Human metabolomics

The identification of the lipids is a very challenging task. The lack of comprehensive mass spectral libraries often limits the identification of compounds in LC-MS and shotgun methods. Some spectral libraries are available, such as the Human Metabolome Database (http /www.hmdb.ca), the METLIN Metabolite Database (http /metlin.scripps.edu) (24), and the MassBank (http /www. massbank.jp) (25). However, construction of universal spectral databases for API-MS is challenging due to the poor reproducibility and high interinstru-ment variability of fragmentation patterns. 

The number of human metabolites has been estimated differently by various scientists. For example, according to Kell [4], the size of the human metabolome is calculated at approximately 2700 metabolites, which are involved in 1100-3300 reactions. This is only an estimated value because the human metabolome has not been thoroughly calculated and substrates for many enzymes have not yet been discovered. Additionally, difficulties in estimation of the appropriate size of the metabolome can be attributed to the fact that many determined metabolites are exogenous in origin (derived from diet or drugs) or derived from endogenous bacterial flora. So far, the online Human Metabolome Database (http //www. hmdb.ca) contains more than 4500 metabohtes detected in human blood and 3995 metabolites detected in human urine. This database is constantly expanded and updated. It is estimated that it will eventually contain more than 10,000 metabolites. 

Wishart DS, Tzur D, Knox C, Eisner R, Guo AC, Young N, Cheng D, Jewell K, Arndt D, Sawhney S, et al. HMDB the Human Metabolome Database. Nucleic Acids Res. 2007 35 D521-526. 

Sources for specific omics studies are also available. For instance, tools such as the RNA-Seq Atlas [17], Human Protein Atlas (HPA) [18], and the Human Metabolome Database (HMDB) [19] are useful for systemic genomic, proteomic, and metabolo-mics studies of human beings. LIPID Metabolites and Pathways Strategy (LIPID MAPS) [20] is a lipidomics gateway, an integrative platform for studies in lipid biology. More resources and updated links can be found at the Biomarkers portal (see Table 1). 

As mixture analysis by NMR is developed, it is increasingly critical to improve NMR small molecule databases. There are currently three main publically accessible small-molecule databases available with NMR data, the Biological Magnetic Resonance Data Bank (BMRB http //www.bmrb.wisc.edu/),78,79 the Madison Metabolomics Consortium Database (MMCD http //mmcd.nmrfam.wisc.edu/),80 and the Human Metabolome Database (HMDB http //www.hmdb.ca/).81 These databases each support searching... 

Metabolomics is often employed in early discovery projects and used for the identification of biomarkers. In mammalian systems, the metabolites so identified are often contained in NMR databases, which, depending on the database, are either commercially or freely available to the public (e.g., Human Metabolome Database).37 There is considerably less nonmammalian NMR information available in these databases. While this is an obvious problem for plant biochemists, it can also impact biomarker discovery utilizing other organisms,... 

Wishart DS (2007) Human Metabolome Database completing the human parts list . Pharmacogenomics 8(7) 683-686... 

Human Metabolome Database (HMDB) KNApSAcK (Comprehensive Species-Metabolite Relationship Database) MassBank... 

Bijlsma, S. et al., Large-scale human metabolomics studies A strategy for data (pre-) processing and validation, Anal. Chem., 78(2), 567, 2006. 

The second example represents a large-scale human metabolomics study that was performed with LC/MS [54]. The aim of this study was to identify potential biomarkers from lipid profiles of some 600 human plasma samples. Lipids were extracted from plasma samples and subjected to LC/ESI-MS analysis. Several different classes of lipids, such as phosphatidylcholines, lysophosphatidyl-cholines, triglycerides, diglycerides, sphingomyelins, and cholesterol esters were the target of this study. To detect small differences in metabolic profiles, statistical methods were used to process this large set of data. Partial least-squares discriminant analysis of the data could locate potential biomarkers. 

Beecher CWW. The human metabolome In Metabolic Profiling Its Role in Biomarker Discovery and Gene Function, Harrogan GG, Ed. Boston, Kluwer Academic, 2003, pp. 311-319. 

Wishart DS, et al. HMDB A knowledgebase for the human metabolome. Nucleic Acids Res 2009 37 D603-D610. 

An insight is provided here into the current state-of-the-art for the compositional analysis of molecules in food utilising high-resolution NMR spectroscopy in conjunction with multivariate data analysis techniques. The recent Human Metabolome Project (http //www.metabolomics.ca) has identified 2,500 metabolites, 1,200 drugs, and 3,500... 

Wishart, D.S., Tzur, D., Knox, C., Eisner, R., Guo, A.C., Young, N., Cheng, D., Jewell, K., Arndt, D., et al. (2007) HMDB the Human Metabolome Database. Nucleic Acid Research, 35 (Database issue), D521-D526. 

Mass spectrometry (MS) is a physical method for analysis introduced more than 100 years ago. During that period, MS applications have successfully proliferated in almost all areas of science and technology— from early studies of the structure of atoms and molecules culminating with the discovery of isotopes to characterization of planetary atmospheres and surfaces and search for extraterrestrial life. MS is an indispensable tool in organic chemistry and biochemistry for structural elucidation of various classes of natural products and synthetic compoimds. In the last quarter century, advances in MS methods and instrumentation have been at the forefront of efforts to map complex biological systems, including the human metabolome, proteome, and microbiome. 

The human metabolome database (HMDB) has been significantly expanded, e.g. the number of purified compounds with NMR, LC-MS and... 

The METLIN metabolite database is implemented using the open-source software tool, MySQL. Most compounds are annotated with both a chemical formula and structure. Individual metabolite is linked to outside resources such as the KEGG, Human Metabolome Database (HMDB), and the respective PubChem database entries through the included numbers of KEGG, HMDB, and Chemical Abstract Service (CAS), respectively. This kind of linkage makes it easy for the researchers to find further references and inquiries about the metabolite. 

R. Ramautar, R. Berger, J. van der Greef and T. Hankemeier, Human Metabolomics Strategies to Understand Biology, Curr. Opin. Chem. Biol, 2013, 17, 841. 

Oral glucose tests have also been investigated by Krug etal, this time for 15 healthy male volunteers [ 101 ]. In fact, this was just one part of a more extensive and comprehensive study to analyse the dynamics of the human metabolome in response to environmental stimuli. 

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