PROTEIN ADDUCTS AS BIOMAKERS OF EXPOSURE TO ORGANOPHOSPHORUS COMPOUNDS

Details

• Alternative Title:
  Toxicology
• Personal Author:
  Marsillach, Judit ; Costa, Lucio G. ; Furlong, Clement E.
• Description:
  Exposure to organophosphorus (OP) compounds can lead to serious neurological damage or death. Following bioactivation by the liver cytochromes P450, the OP metabolites produced are potent inhibitors of serine active-site enzymes including esterases, proteases and lipases. OPs may form adducts on other cellular proteins. Blood cholinesterases (ChEs) have long served as biomarkers of OP exposure in humans. However, the enzymatic assays used for biomonitoring OP exposures have several drawbacks. A more useful approach will focus on multiple biomarkers and avoid problems with the enzymatic activity assays. OP inhibitory effects result from a covalent bond with the active-site serine of the target enzymes. The serine OP adducts become irreversible following a process referred to as aging where one alkyl group dissociates over variable lengths of time depending on the OP adduct. The OP-adducted enzyme then remains in circulation until it is degraded, allowing for a longer window of detection compared with direct analysis of OPs or their metabolites. Mass spectrometry (MS) provides a very sensitive method for identification of post-translational protein modifications. MS analyses of the percentage adduction of the active-site serine of biomarker proteins such as ChEs will eliminate the need for basal activity levels of the individual and will provide for a more accurate determination of OP exposure. MS analysis of biomarker proteins also provides information about the OP that has caused inhibition. Other useful biomarker proteins include other serine hydrolases, albumin, tubulin and transferrin.
• Subjects:
  Acetylcholinesterase Butyrylcholinesterase Carboxylesterase Environmental Exposure Humans Organophosphorus Compounds Peptide Hydrolases Proteins Serum Albumin
• Source:
  Toxicology. 2012; 307:46-54.
• Pubmed ID:
  23261756
• Pubmed Central ID:
  PMC3747771
• Document Type:
  Journal Article
• Funding:
  R01 ES009883/ES/NIEHS NIH HHS/United States ; P42 ES004696/ES/NIEHS NIH HHS/United States ; ES09883/ES/NIEHS NIH HHS/United States ; ES07033/ES/NIEHS NIH HHS/United States ; P41 RR011823/RR/NCRR NIH HHS/United States ; P30 ES007033/ES/NIEHS NIH HHS/United States ; ES09601/EPA-R826886/ES/NIEHS NIH HHS/United States ; ES04696/ES/NIEHS NIH HHS/United States ; P01 ES009601/ES/NIEHS NIH HHS/United States
• Volume:
  307
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:95a29e247f480bd845e70c5c043e440a566356ae5e9e7d5c4bd817672f5d3e68
• Download URL:
  https://stacks.cdc.gov/view/cdc/52348/cdc_52348_DS1.pdf
• File Type:
  [PDF - 752.61 KB ]