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) |
|---|---|
| Title of host publication | Handbook of Toxicology of Chemical Warfare Agents: Second Edition |
| Publisher | Elsevier Inc. |
| Pages | 953-965 |
| Number of pages | 13 |
| ISBN (Print) | 9780128001592 |
| DOIs | |
| State | Published - Jan 21 2015 |
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Keywords
- Aging
- Albumin
- Biomarkers
- Chemical warfare agents
- Chlorpyrifos
- Dichlorvos
- Mass spectrometry
- Nerve agents
ASJC Scopus subject areas
- Medicine(all)
Cite this
Biomarkers of Exposure to Organophosphorus Poisons : A New Motif for Covalent Binding to Tyrosine in Proteins That Have No Active Site Serine. A New Motif for Covalent Binding to Tyrosine in Proteins That Have No Active Site Serine. / Lockridge, Oksana; Schopfer, Lawrence M; Masson, Patrick.
Handbook of Toxicology of Chemical Warfare Agents: Second Edition. Elsevier Inc., 2015. p. 953-965.Research output: Chapter in Book/Report/Conference proceeding › Chapter
}
TY - CHAP
T1 - Biomarkers of Exposure to Organophosphorus Poisons
T2 - A New Motif for Covalent Binding to Tyrosine in Proteins That Have No Active Site Serine. A New Motif for Covalent Binding to Tyrosine in Proteins That Have No Active Site Serine
AU - Lockridge, Oksana
AU - Schopfer, Lawrence M
AU - Masson, Patrick
PY - 2015/1/21
Y1 - 2015/1/21
N2 - 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.
AB - 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.
KW - Aging
KW - Albumin
KW - Biomarkers
KW - Chemical warfare agents
KW - Chlorpyrifos
KW - Dichlorvos
KW - Mass spectrometry
KW - Nerve agents
UR - http://www.scopus.com/inward/record.url?scp=84966784738&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84966784738&partnerID=8YFLogxK
U2 - 10.1016/B978-0-12-800159-2.00064-6
DO - 10.1016/B978-0-12-800159-2.00064-6
M3 - Chapter
SN - 9780128001592
SP - 953
EP - 965
BT - Handbook of Toxicology of Chemical Warfare Agents: Second Edition
PB - Elsevier Inc.
ER -