title: Proteomic analysis of adducted butyrylcholinesterase for biomonitoring organophosphorus exposures.
abstract: Organophosphorus (OP) compounds include a broad group of toxic chemicals such as insecticides, chemical warfare agents and antiwear agents. The liver cytochromes P450 bioactivate many OPs to potent inhibitors of serine hydrolases. Cholinesterases were the first OP targets discovered and are the most studied. They are used to monitor human exposures to OP compounds. However, the assay that is currently used has limitations. The mechanism of action of OP compounds is the inhibition of serine hydrolases by covalently modifying their active-site serine. After structural rearrangement, the complex OP inhibitor-enzyme is irreversible and will remain in circulation until the modified enzyme is degraded. Mass spectrometry is a sensitive technology for analyzing protein modifications, such as OP-adducted enzymes. These analyses also provide some information about the nature of the OP adduct. Our aim is to develop high-throughput protocols for monitoring OP exposures using mass spectrometry.
authors.affiliation: Dept of Medicine (Division of Medical Genetics), University of Washington, 98195 Seattle, WA, USA. jmarsi@uw.edu
authors.forename: Judit
authors.initials: J
authors.lastname: Marsillach
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Hsieh
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Richter
authors.forename: Michael J
authors.initials: MJ
authors.lastname: MacCoss
authors.forename: Clement E
authors.initials: CE
authors.lastname: Furlong
mesh_terms: D000383:Agriculture; D002091:Butyrylcholinesterase / Q000737:chemistry / Q000378:metabolism*; D020134:Catalytic Domain; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D004781:Environmental Exposure; D004784:Environmental Monitoring / Q000379:methods*; D057166:High-Throughput Screening Assays / Q000379:methods; D006801:Humans; D016273:Occupational Exposure; D009943:Organophosphorus Compounds / Q000633:toxicity*; D040901:Proteomics; D012694:Serine / Q000737:chemistry; D053719:Tandem Mass Spectrometry
chemical_list: D002800:Cholinesterase Inhibitors; D009943:Organophosphorus Compounds; D012694:Serine; D002091:Butyrylcholinesterase