title: Discovery of Cell-Type-Specific and Disease-Related Enzymatic Activity Changes via Global Evaluation of Peptide Metabolism.
abstract: Cellular homeostasis is maintained by a complex network of reactions catalyzed by enormous numbers of enzymatic activities (the enzymome), which serve to determine the phenotypes of cells. Here, we focused on the enzymomics of proteases and peptidases because these enzymes are an important class of disease-related proteins. We describe a system that (A) simultaneously evaluates metabolic activities of peptides using a series of exogenous peptide substrates and (B) identifies the enzymes that metabolize the specified peptide substrate with high throughput. We confirmed that the developed system was able to discover cell-type-specific and disease-related exo- and endopeptidase activities and identify the responsible enzymes. For example, we found that the activity of the endopeptidase neurolysin is highly elevated in human colorectal tumor tissue samples. This simple but powerful enzymomics platform should be widely applicable to uncover cell-type-specific reactions and altered enzymatic functions with potential value as biomarkers or drug targets in various disease states and to investigate the mechanisms of the underlying pathologies.
authors.forename: Jun
authors.initials: J
authors.lastname: Onagi
authors.affiliation: Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency (JST) , 4-1-8 Honcho Kawaguchi, Saitama 332-0012, Japan.
authors.forename: Toru
authors.identifier: 0000-0002-9268-6964
authors.initials: T
authors.lastname: Komatsu
authors.forename: Yuki
authors.initials: Y
authors.lastname: Ichihashi
authors.forename: Yugo
authors.initials: Y
authors.lastname: Kuriki
authors.affiliation: Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency (JST) , 4-1-8 Honcho Kawaguchi, Saitama 332-0012, Japan.
authors.forename: Mako
authors.initials: M
authors.lastname: Kamiya
authors.forename: Takuya
authors.identifier: 0000-0002-3425-3589
authors.initials: T
authors.lastname: Terai
authors.forename: Tasuku
authors.initials: T
authors.lastname: Ueno
authors.forename: Kenjiro
authors.identifier: 0000-0003-0797-4038
authors.initials: K
authors.lastname: Hanaoka
authors.forename: Hiroyuki
authors.identifier: 0000-0001-8521-3029
authors.initials: H
authors.lastname: Matsuzaki
authors.forename: Keisuke
authors.initials: K
authors.lastname: Hata
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Watanabe
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Nagano
authors.affiliation: Core Research for Evolutional Science and Technology (CREST) Investigator, Japan Agency for Medical Research and Development (AMED) , 1-7-1 Otemachi, Chiyoda-ku, Tokyo 100-0004, Japan.
authors.forename: Yasuteru
authors.initials: Y
authors.lastname: Urano
mesh_terms: D045744:Cell Line, Tumor; D010450:Endopeptidases / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008968:Molecular Conformation; D009928:Organ Specificity; D010447:Peptide Hydrolases / Q000737:chemistry / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*
chemical_list: D010455:Peptides; D010450:Endopeptidases; D010447:Peptide Hydrolases