Metabolome/metabolomics

Shurubor, Y.I. et al., Analytical precision, biological variation, and mathematical normalization in high data density metabolomics, Metabolomics, 1(1), 75, 2005. 

Metabolomics is the technology behind the measurement of metabolite concentrations, fluxes, and secretions in cells and tissues (metabolome). Metabolomics is at the cross-roads of genotype/phenotype interactions, where the interrelationship of metabolic pathways is considered to be the fundamental component of an organism s phenotype. Metabolomics is distinguished by the fact that metabolites are not directly linked to the genetic code but actually are products of a concerted action of many enzyme networks and other regulatory proteins (243). Metabolites also are more complex than nucleic acids, which are composed of four nucleotides, or proteins, which in turn are composed of 20 different amino acids. As a result, metabolites cannot be... 

Mihaleva VV, Vorst O, Maliepaard C, Verhoeven HA, de Vos RCH, Hall RD, van Ham RCHJ. Accurate mass error correction in liquid chromatography time-of-flight mass spectrometry based metabolomics. Metabolomics 2008 4 171-182. 

Boudonck KJ, et al. Characterization of the biochemical variability of bovine milk using metabolomics. Metabolomics 2009 5 1-12. 

Teng Q, et al. A direct cell quenching method for cell-culture based metabolomics. Metabolomics 2009 5 199-208. 

Bovy, A., Schijlen, E. Hall, R.D. (2007). Metabolic engineering of flavonoids in tomato (Solanum lycopersicum) the potential for metabolomics. Metabolomics, 3, 399-412. 

Evaluation of metabolite extraction strategies from tissue samples using NMR metabolomics. Metabolomics 3 55 7... 

Goodacre R, Broadhurst D, Smilde AK, Kristal BS, Baker JD, Beger R, et al. Proposed minimum reporting standards for data analysis in metabolomics. Metabolomics 2007 3 231-41. 

Kell DB. Metabolomics and systems biology making sense of the soup. Curr Opin Microbiol 2004 7 296-307. 

These seemingly simple questions have profound implications because they ask us to examine possibly obsolete policies and behaviors that have become deeply ingrained and unexamined habit patterns. For instance, let us consider the fields of genomics, proteomics, metabolomics, and systems biology as applied to pharmaceutical R D ... 

Metabolomics studies the entire metabolism of an organism. It is possible to consider characterising the complex pattern of cellular proteins and metabolites that are excreted in urine. Pattern recognition techniques of nuclear magnetic resonance spectra have been applied to determine the dose-response using certain classical liver and kidney toxicants (Robertson et al, 2000). This could well provide a signature of the functional state of the kidney, and perturbations in the pattern as a result of exposure to a chemical could be observed. But first it would be necessary to understand how compounds with known effects on the kidney affect these processes. 

Adjunctive to flux control analysis, other components of metabolism that contribute to product accumulation are needed including (1) substrate/precursor pool sizes (metabolomics), (2) co-factor capacities (metabolomics), (3) gene expression profiles (transcriptomics and quanfifafive real-time PCR), (4) protein profiles (pro-... 

Several observations lend credence to the rationale of monitoring cellular activities at the level of the proteins (proteomes) and metabolites (metabolomes). Some are listed below ... 

Several biochemical events occur posttranscriptionally that define the response of cells to stimuli. For instance, alternative splicing, posttrans-lational modifications, regulation of enzyme activities, distribution of metabolites between cellular compartments, necessitate analysis at the level of the proteome and the metabolome. 

Thus there is sufficient ground to cover at the functional level even after successful genetic characterizations that justifies the development of technologies for functional genomics, especially for high-throughput monitoring of proteomes and metabolomes. 

Maharjan, R. P. Ferenci,T. Global metabolite analysis the influence of extraction methodology on metabolome profiles of Escherichia coli. Anal. Biochem. 2003,313, 154-154. 

Castrillo, J. L. Hayes, A. Mohammed, S. Gaskell, S. J. Oliver, S. G. An optimized protocol for metabolome analysis in yeast using direct infusion electrospray mass spectrometry. Phytochemistry 2003, 62, 929-937. 

Porter, S.E.G., Stoll, D.R., Rutan, S.C., Carr, P.W., Cohen, J.D. (2006). Analysis of four-way two-dimensional liquid chromatography-diode array data application to metabolomics. Anal. Chem. 78, 5559-5569. 

Other applications that utilize different types of reversed-phase columns in both dimensions have been advocated by Carr (Stoll et al., 2006) for metabolomics work in small-molecule separations. These stationary phases include a pentafluorophenyl-propyl stationary phase in the first dimension and a carbon-coated zirconia material stationary phase in the second dimension. A common mistake in 2D method development is to mismatch the solvent system the two solvent systems must be miscible as discussed below. 

Recent proteomic or metabolomic analyses often require the separation/identification of several hundreds to several thousands of species in a mixture using LC-MS. It is practically impossible to achieve complete separation for a sample with complexity of... 

Tolstikov, V.V., Lommen, A., Nakanishi, K., Tanaka, N., Fiehn, O. (2003). Monolithic silica-based capillary reversed-phase liquid chromatography/electrospray mass spectrometry for plant metabolomics. Anal. Chem. 75, 6737-6740. 

Antoniewicz, M.R., Stephanopoulos, G., and Kelleher, J.K., Evaluation of regression models in metabolic physiology Predicting fluxes from isotopic data without knowledge of the pathway, Metabolomics 2,41, 2006. 

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