Proteomic analysis of adducted butyrylcholinesterase for biomonitoring organophosphorus exposures

Details

• Alternative Title:
  Chem Biol Interact
• Personal Author:
  Marsillach, Judit ; Hsieh, Edward J. ; Richter, Rebecca J. ; MacCoss, Michael J. ; Furlong, Clement E.
• 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.
• Subjects:
  Agriculture Catalytic Domain Cholinesterase Inhibitors Environmental Exposure Environmental Monitoring High-Throughput Screening Assays Humans Occupational Exposure Organophosphorus Compounds Proteomics Serine Tandem Mass Spectrometry

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• Source:
  Chem Biol Interact. 2012; 203(1):85-90.
• Pubmed ID:
  23123252
• Pubmed Central ID:
  PMC4108156
• Document Type:
  Journal Article
• Funding:
  P41 GM103533/GM/NIGMS NIH HHS/United States ; R01 ES009883/ES/NIEHS NIH HHS/United States ; P42 ES004696/ES/NIEHS NIH HHS/United States ; 5P42ES04696/ES/NIEHS NIH HHS/United States ; R01 GM103551/GM/NIGMS NIH HHS/United States ; NIEHS P30ES07033/ES/NIEHS NIH HHS/United States ; P30 ES007033/ES/NIEHS NIH HHS/United States ; ES09601/EPA-R826886/ES/NIEHS NIH HHS/United States ; P41GM103533/GM/NIGMS NIH HHS/United States ; P01 ES009601/ES/NIEHS NIH HHS/United States ; R01ES09883/ES/NIEHS NIH HHS/United States
• Volume:
  203
• Issue:
  1
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:7bd58a362a6abff24c7e00a2082f2dc50a3d1e4cd2c33820181856849dc65faa
• Download URL:
  https://stacks.cdc.gov/view/cdc/52349/cdc_52349_DS1.pdf
• File Type:
  [PDF - 253.26 KB ]