Which enzyme is primarily inhibited by organophosphate compounds, leading to accumulation of acetylcholine at the neuromuscular junction?

Explanation

## Mechanism of Organophosphate Toxicity **Key Point:** Organophosphates irreversibly phosphorylate the serine residue in the active site of acetylcholinesterase (AChE), preventing hydrolysis of acetylcholine. ### Enzyme Target Organophosphates bind covalently to the esterase site of acetylcholinesterase, forming a stable phosphoester bond. This prevents the enzyme from breaking down acetylcholine, leading to its accumulation at synapses and neuromuscular junctions. ### Pathophysiology Accumulated acetylcholine causes: - Excessive stimulation of muscarinic receptors (parasympathetic overstimulation) - Excessive stimulation of nicotinic receptors (muscle fasciculations, paralysis) - CNS effects (confusion, seizures, respiratory depression) **High-Yield:** The inhibition is **irreversible** unless pralidoxime (2-PAM) is given early to reactivate the enzyme before "aging" occurs (typically within 24–48 hours depending on the agent). ### Related Enzymes While butyrylcholinesterase and pseudocholinesterase (plasma cholinesterase) are also inhibited by organophosphates, they are not the primary target in the nervous system. AChE is the critical enzyme at the neuromuscular junction and synapses. [cite:Parikh Forensic Medicine & Toxicology Ch 19]