Chem Biol Interact

Abstract

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.P41 GM103533/GM/NIGMS NIH HHS/United StatesR01 ES009883/ES/NIEHS NIH HHS/United StatesP42 ES004696/ES/NIEHS NIH HHS/United States5P42ES04696/ES/NIEHS NIH HHS/United StatesR01 GM103551/GM/NIGMS NIH HHS/United StatesNIEHS P30ES07033/ES/NIEHS NIH HHS/United StatesP30 ES007033/ES/NIEHS NIH HHS/United StatesES09601/EPA-R826886/ES/NIEHS NIH HHS/United StatesP41GM103533/GM/NIGMS NIH HHS/United StatesP01 ES009601/ES/NIEHS NIH HHS/United StatesU54 OH007544/OH/NIOSH CDC HHS/United StatesR01ES09883/ES/NIEHS NIH HHS/United States2014-07-23T00:00:00Z23123252PMC4108156vault:2748