Acetylcholinesterase (AChE or acetylhydrolase) is a hydrolase that hydrolyzes the neurotransmitter acetylcholine. AChE is found at mainly neuromuscular junctions and cholinergic brain synapses, where its activity serves to terminate synaptic transmission. It belongs tocarboxylesterase family of enzymes. It is the primary target of inhibition by organophosphorus compounds such as nerve agents and pesticides. AChE has a very high catalytic activity - each molecule of AChE degrades about 25000 molecules ofacetylcholine (ACh) per second, approaching the limit allowed by diffusion of the substrate. ACh is released from the nerve into the synaptic cleft and binds to ACh receptors on the post-synaptic membrane, relaying the signal from the nerve. AChE, also located on the post-synaptic membrane, terminates the signal transmission by hydrolyzing ACh. The liberated choline is taken up again by the pre-synaptic nerve and ACh is synthetized by combining with acetyl-CoA through the action of choline acetyltransferase.
Chlorpyrifos is an organophosphate insecticide that is classified as a phosphorothionate. The oxon metabolite of Chlorpyrifos is an inhibitor of acetylcholinesterase (AChE), affecting neurological function in insects, humans, and other animals. The Chlorpyrifos oxon (CPO) metabolite is hydrolyzed by the plasma enzyme paraoxonase 1 (PON1), and susceptibility to neurotoxicity associated with CPO exposure is mitigated by PON1 overexpression.
