Opportunities in Metabolomics

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Opportunities in Metabolomics
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Conlon, Michael
University of Florida
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Gainesville, FL
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Opportunities for Metabolomics Metabolomics is the scientific study of chemical processes involving metabolites. Specifically, metabolomics is the systematic study of the unique chemical fingerprints that specific cellular processes leave behind, the study of their small molecule metabolite profiles. The metabalome represents the collection of all metabolites in a biological cell, tissue, organ or organism, which are the end products of cellular processes. Art Edison, Rick Yost, Lauren McIntyre, Tim Garrett, Mike Conlon, Alisha Mitchell Roberts, Alicia Turner, Tim Janicki Metabolomics in Plant Science SECIM, the Southeast Center for Integrated Metabolomics, is funded in part by the National Institutes of Health grant U24 DK097209, by the Clinical and Translational Science Institute, funded in part by NIH award UL1 TR000064, by the UF Office of Research and the UF Institute for Food and Agricultural Sciences Riboflavin is the substrate for biosynthesis of the essential flavocoenzymes FMN and FAD, which occur in all kingdoms of life and have roles in diverse redox reactions as well as in other processes such as DNA repair, light sensing, and bioluminescence. Biosynthesis of riboflavin is well known in prokaryotes but in plants gene for reductase step ( PyrR ) was missing. In E. coli the deamination and reduction steps are catalyzed by a single bifunctional enzyme, RibD which has N terminal deaminase and C termin al reductase domains. Bioinformatics analysis indicated a putative candidate gene for PyrR in maize (GRM ZM 2G 090068 ). Mass Spectrometric Imaging of Potential Biomarkers for Myocardial Infarction. An innovative approach for metabolomics studies is mass spectrometric imaging, in which a microscopically focused laser beam generates chemically selective images from tissue. We have employed this method to identify and image potential biomarkers of myocardial infarction following a left anterior descending (LAD) coronary artery ligation in an in vivo rat model. Figure 1 The first four steps of the riboflavin biosynthesis pathway in bacteria and plants. The enzymes involved are GTP cyclohydrolase II ( RibA ), pyrimidine deaminase ( Deam ), pyrimidine reductase (Red), and a specific phosphatase ( Pase ). Enzymes for which the plant genes are not known are colored red. Intermediates are: 1 2 5 diamino 6 ribosylamino 4 ( 3 H ) pyrimidinone 5 phosphate; 2 5 amino 6 ribosylamino 2 4 ( 1 H 3 H ) pyrimidinedione 5 phosphate; 3 5 amino 6 ribitylamino 2 4 ( 1 H 3 H ) pyrimidinedione 5 phosphate; 4 5 amino 6 ribitylamino 2 4 ( 1 H 3 H ) pyrimidinedione Reductase in the Plant Hasnaim O Frelin S Roje KW Ellens K Ali, J Guan, TJ Garrett, V de Grcy Lagard JF Gregory III, DR McCarty, and AD Hanson Plant Physiology 161 (1), 48 56 (2013). We have shown that nematodes convert information from external conditions such as food availability, population density, temperature, primary metabolism of the animals Srinivasan et al. Nature 2008 454 1115 1118; Srinivasan et al. PLoS Biol 2012 10 e1001237; Edison A. S. Curr Opin Neurobiol 2009 19 378 388. Metabolomics i n Animals Nematodes employ a complex chemical language that regulates multiple behaviors. We have used NMR and LC MS to identify several pheromones from several species of nematode that lead to male or female specific attraction. specific mating pheromones in the nematode Panagrellus redivivus A Choe T Chuman SH von Reuss AT Dossey JJ Yim R Ajredini AA Kolawa F Kaplan HT Alborn PEA Teal FC Schroeder PW Sternberg and AS Edison, PNAS, 109 (51), 20949 20954 (2012). Metabolomics And Clinical Biomarkers Goal: to identify biomarkers of myocardial infarc tion directly in heart tissue following ligation of the coronary artery in a rat (TTC stains healthy tissue red ) Water soluble metabolites such as creatine (M+H + ion at m/z 132 ) leak from the plasma membrane, d ecreasing their concentration in infarcted tissue Lysophospholipids such as LPC 18:0 ( M+Na + ion at m/z 504) localize within infarcted tissue Triacylglycerides such as TAG 16:0/18:1/18:2 the area of infarction Menger W.L. Stutts D. Anbukumar J.A. Bowden, D.A.Ford and R.A. Yost, Anal. Chem ., 84 1117 1125 (2012).