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Mining the Metabolome
Education and Metabolism & Energy Tracks

The sequencing of the human genome has provided an opportunity for the discovery of novel peptide ligands for orphan G protein coupled receptors and other proteins potentially involved in the physiologic regulation of metabolism. Using bioinformatics Dr. Hsueh searched for orthologs of known peptide hormones and discovered embedded in the ghrelin-prohormone a second biologically active peptide, obestatin. Dr. Hsueh has provided evidence that the receptors for ghrelin and obestatin evolved from a common ancestral gene but diverged into opposing functions responsible for the maintenance of body weight balance. Dr. Mori employed bioinformatics coupled with subtraction cloning of peroxisome proliferators-activated receptor gamma-stimulated genes in brain and adipocytes to identify a novel, endogenous, appetite regulating peptide, nesfatin. Further, Dr. Mori  has demonstrated the interaction of nesfatin with known hypothalamic peptides recognized as major regulators of appetite and metabolism. Dr. Hsu employed phylogenetic screening to identify a novel member of the calcitonin gene related peptide/adrenomedullin gene familty, intermedin. Candidate sequences were identified to have catalytic processing sites that would yield homologous peptides, and the essential signal peptide sequence in the N terminus. In addition to expanding our knowledge of the function of the CGRP/AM family of peptides, intermedin has been demonstrated to be a potent anorexigenic agent and to have significant effects on autonomic function. This symposium will provide a forum for the description of the available  (and proven successful) tools for the bioinformatics and proteomic mining of the metabolome, demonstrating not only the power of those technologies but also the potential for the future discovery of additional proteins involved in the physiologic regulation of metabolism.