lacétylcholinestérase

Lacétylcholinestérase, also known as acetylcholinesterase (AChE), is a serine hydrolase enzyme that rapidly hydrolyzes the neurotransmitter acetylcholine in cholinergic synapses and at the neuromuscular junction. By breaking down acetylcholine, it terminates signaling and regulates the timing of synaptic transmission. The enzyme is located in the synaptic membrane and exists in multiple molecular forms, including tetrameric AChE-T and glycosylphosphatidylinositol-anchored AChE-GPI variants, often assembled with a collagen-like tail in vertebrates.

The catalytic mechanism features a serine-histidine-glutamate triad within a hydrophobic catalytic gorge that guides acetylcholine to the serine residue for hydrolysis, yielding choline and acetate. In humans, AChE is highly concentrated at neuromuscular junctions and central and peripheral synapses, with tissue-specific distribution of its molecular forms.

Physiological and clinical significance: AChE ensures rapid termination of cholinergic signaling, enabling precise control of muscle contraction and cognitive processes. Pharmacological modulation of AChE has therapeutic value: acetylcholinesterase inhibitors such as donepezil, rivastigmine, and galantamine are used to treat Alzheimer’s disease by increasing brain acetylcholine levels; inhibitors like pyridostigmine are used to treat myasthenia gravis. Conversely, organophosphates and nerve agents irreversibly inhibit AChE, causing cholinergic excess and requiring antidotal treatment with atropine and oximes (e.g., pralidoxime) to restore enzyme activity.

Lacétylcholinestérase is distinct from butyrylcholinesterase (pseudocholinesterase), a related serine hydrolase with broader substrate specificity. Defects or pharmacological inhibition can impair neuromuscular transmission or lead to excessive cholinergic activity.