Acetylcholinesterase

[16] The esteratic subsite, where acetylcholine is hydrolyzed to acetate and choline, contains the catalytic triad of three amino acids: serine 203, histidine 447 and glutamate 334.

Then, the acyl-enzyme undergoes nucleophilic attack by a water molecule, assisted by the histidine 440 group, liberating acetic acid and regenerating the free enzyme.

[20] Overall, in mammals, AChE is primarily involved in the termination of impulse transmission at cholinergic synapses by rapid hydrolysis of the neurotransmitter acetylcholine.

[24][25] A cholinomimetic drug disrupts this process by acting as a cholinergic neurotransmitter that is impervious to acetylcholinesterase's lysing action.

[26] Irreversible inhibitors of AChE may lead to muscular paralysis, convulsions, bronchial constriction, and death by asphyxiation.

[27] Cleavage of OP by AChE leaves a phosphoryl group in the esteratic site, which is slow to be hydrolyzed (on the order of days) and can become covalently bound.

Reversible inhibitors occupy the esteratic site for short periods of time (seconds to minutes) and are used to treat of a range of central nervous system diseases.

[39] Acetylcholinesterase exists in multiple molecular forms, which possess similar catalytic properties, but differ in their oligomeric assembly and mode of attachment to the cell surface.

Note higher vertebrates also encode a closely related paralog BCHE (butyrylcholinesterase) with 50% amino acid identity to ACHE.

[40] Diversity in the transcribed products from the sole mammalian gene arises from alternative mRNA splicing and post-translational associations of catalytic and structural subunits.

The other, alternatively spliced form expressed primarily in the erythroid tissues, differs at the C-terminus, and contains a cleavable hydrophobic peptide with a PI-anchor site.

[45] Exposure to acetylcholinesterase inhibitors is one of several studied explanations for the chronic cognitive symptoms veterans displayed after returning from the Gulf War.

Studying acetylcholine levels using microdialysis and HPLC-ECD, researchers at the University of South Carolina School of Medicine determined PB, when combined with a stress element can lead to cognitive responses.

AChe mechanism of action [ 5 ]
Mechanism of Inhibitors of AChE