Opportunities for Metabolomics

1. Opportunities for Metabolomics Art Edison, Rick Yost, Lauren McIntyre, Tim Garrett, Mike Conlon, Alisha Mitchell-Roberts, Alicia Turner, Tim Janicki 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 metabalomerepresents the collection of all metabolites in a biological cell, tissue, organ or organism, which are the end products of cellular processes. Metabolomics in Plant Science Metabolomics in Animals Metabolomics And Clinical Biomarkers 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. 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-termin­al reductase domains. Bioinformatics analysis indicated a putative candidate gene for PyrR in maize (GRM­ZM­2G­090068). Nematodes employ a complex chemical language that regulates multiple behaviors. • Goal: to identify biomarkers of myocardial infarc-tiondirectly 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, decreasing their concentration in infarcted tissue We have shown that nematodes convert information from external conditions such as food availability, population density, temperature, etc. into chemical pheromone signals that modify behavior. The “black box” converting the input to output is the primary metabolism of the animals. Srinivasan, et al. Nature2008, 454, 1115–1118; Srinivasan, et al. PLoSBiol2012, 10, e1001237; Edison, A. S. Curr. Opin. Neurobiol.2009, 19, 378–388. Lysophospholipids such as LPC 18:0 (M+Na+ ion at m/z 504) localize within infarcted tissue 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(3H)-pyrimidinone 5′-phosphate; 2, 5-amino-6-ribosylamino-2,4(1H,3H)-pyrimidinedione 5′-phosphate; 3, 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione 5′-phosphate; 4, 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione. Triacylglycerides such as TAG 16:0/18:1/18:2 (m/z 879) localize in the “at risk” region, around the area of infarction We have used NMR and LC-MS to identify several pheromones from several species of nematode that lead to male- or female-specific attraction. “Sex-specific mating pheromones in the nematode Panagrellusredivivus,” 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, andAS Edison, PNAS,109(51),20949-20954 (2012). “Identification and Characterization of the Missing Pyrimidine Reductase in the Plant Riboflavin Biosynthesis Pathway,” G Hasnaim, O Frelin, S Roje, KW Ellens, K Ali, J Guan, TJ Garrett, V de Grécy-Lagard, JF Gregory III, DR McCarty, and AD Hanson Plant Physiology, 161(1), 48-56 (2013). “MALDI Mass Spectrometric Imaging of Cardiac Tissue Following Myocardial Infarction in a Rat Coronary Artery Ligation Model”, R.F. Menger, W.L. Stutts, D. Anbukumar, J.A. Bowden, D.A.Ford, and R.A. Yost, Anal. Chem., 84, 1117-1125 (2012). 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.