Chapter 64 - Biomarkers of Exposure to Organophosphorus Poisons: A New Motif for Covalent Binding to Tyrosine in Proteins That Have No Active Site Serine

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.