Proteomic Analysis of Adducted Butyrylcholinesterase for Biomonitoring Organophosphorus Exposures

Details

• Personal Author:
  Furlong CE ; Hsieh EJ ; MacCoss MJ ; Marsillach J ; Richter RJ
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Enzymes Insecticides Occupational Health Safety
• Keywords:
  Author Keywords: Organophosphates Biomonitoring Butyrylcholinesterase Enzyme Activity Mass Spectrometry Organophosphorus Compounds Protein Adducts Protein Biochemistry Proteins
• ISSN:
  0009-2797
• Document Type:
  Text
• Funding:
  Cooperative Agreement
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 10 ; Washington
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  85-90
• Volume:
  203
• Issue:
  1
• NIOSHTIC Number:
  nn:20053334
• Citation:
  Chem-Biol Interact 2013 Mar; 203(1):85-90
• Contact Point Address:
  Clement E. Furlong, Dept. of Medicine (Division of Medical Genetics), University of Washington, 1959 NE Pacific St., HSB Room I-204A, Box 357720, 98195 Seattle, WA, USA
• Email:
  clem@uw.edu
• Federal Fiscal Year:
  2013
• NORA Priority Area:
  Agriculture, Forestry and Fishing
• Performing Organization:
  University of Washington
• Peer Reviewed:
  True
• Start Date:
  20010930
• Source Full Name:
  Chemico-Biological Interactions
• End Date:
  20270929
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:65c67dc20dbad207caf380fad5ffacae4b6ae2c90a8a6e8a2786fc6e29db183de3c338b2fcaf025a75cde3f3521a49265efb40ad05af2d060d928896ac09853f
• Download URL:
  https://stacks.cdc.gov/view/cdc/216118/cdc_216118_DS1.pdf
• File Type:
  [PDF - 764.67 KB ]