Organophosphate (OP) poisoning becomes refractory to oxime therapy (pralidoxime) once 'ageing' of the OP-AChE complex occurs. The mechanism of ageing involves:

• A Hydrolysis of the phosphoester bond releasing free acetylcholinesterase
• B Proteolytic cleavage of the enzyme active site by lysosomal enzymes
• C Conformational change in butyrylcholinesterase permanently inactivating it
• D Dealkylation of the phosphorylated serine residue in acetylcholinesterase, converting it to a monoalkyl phosphoryl enzyme ✓

Explanation

Ageing of the OP-AChE complex occurs by dealkylation (loss of one alkyl group from the phosphoryl moiety attached to the serine-200 residue of acetylcholinesterase), converting the dialkyl phosphoryl-enzyme to a monoalkyl phosphoryl-enzyme that is resistant to nucleophilic attack by oximes. Once aged, pralidoxime cannot reactivate the enzyme because the remaining negative charge on the phosphorus repels the nucleophilic oxime. The rate of ageing varies by OP compound — soman ages within minutes while parathion takes hours.

Reference: The Essentials of Forensic Medicine and Toxicology (Narayan Reddy), 34th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.