Organophosphorus oxon compounds (OP oxons)

Organophosphorus oxon compounds are the highly reactive, oxygenated metabolites of organophosphate (OP) pesticides and nerve agents. While many OPs are applied or encountered in their 'thion' (P=S) form, they undergo metabolic activation via cytochrome P450 enzymes to the 'oxon' (P=O) form, which possesses significantly higher toxicity (PubChem). These compounds are potent inhibitors of serine hydrolases, most notably acetylcholinesterase (AChE), which is responsible for terminating nerve impulses by breaking down acetylcholine. By forming a stable covalent bond with the active site of AChE, oxons cause a toxic buildup of acetylcholine, leading to a cholinergic crisis characterized by miosis, salivation, bronchospasm, and muscle paralysis (StatPearls, 2023). Understanding the kinetics of oxon formation and their interaction with cholinesterases is critical for developing effective antidotes and managing pesticide exposure (PubMed, 2021). Furthermore, the 'aging' process, where the oxon-enzyme complex loses an alkyl group, renders the inhibition irreversible and resistant to oxime reactivation (CDC, 2023).

Other names

Organophosphate oxonsP=O organophosphatesOxon metabolitesPhosphorothioate oxon derivatives

Organophosphorus oxons act as irreversible inhibitors of the enzyme acetylcholinesterase (AChE). They function by phosphorylating the hydroxyl group of the serine residue within the enzyme's active site (StatPearls, 2023). This covalent bond prevents the enzyme from hydrolyzing the neurotransmitter acetylcholine, leading to its accumulation in the synaptic cleft and subsequent overstimulation of muscarinic and nicotinic receptors (CDC, 2023). Antidotes like pralidoxime work by dephosphorylating the enzyme, while atropine antagonizes the muscarinic effects of accumulated acetylcholine.