Abstract
Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are not the only protein targets of organophosphorus (OP) agent exposure in humans. Doses too low to inhibit AChE are neurotoxic to some humans, suggesting that other proteins are also modified. Mass spectrometry (MS) analysis shows that tyrosine in purified proteins and small synthetic peptides creates stable covalent bonds with OP compounds. A new, tyrosine-based motif for OP agent binding to proteins is proposed. An example of this motif is the binding of OP agents to albumin at tyrosine 411. MS has detected albumin adducts in humans who deliberately poisoned themselves with dichlorvos or chlorpyrifos. Antibodies to OP adducts on tyrosine are expected to be useful for detecting exposure and for identifying new biomarkers of exposure.
Original language | English (US) |
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Title of host publication | Handbook of Toxicology of Chemical Warfare Agents |
Subtitle of host publication | Second Edition |
Publisher | Elsevier Inc. |
Pages | 953-965 |
Number of pages | 13 |
ISBN (Print) | 9780128001592 |
DOIs | |
State | Published - Jan 21 2015 |
Keywords
- Aging
- Albumin
- Biomarkers
- Chemical warfare agents
- Chlorpyrifos
- Dichlorvos
- Mass spectrometry
- Nerve agents
ASJC Scopus subject areas
- General Medicine