acetýlkolínesterasa

Acetýlkolínesterasa, also known as acetylcholinesterase (AChE), is a serine hydrolase that rapidly hydrolyzes the neurotransmitter acetylcholine into choline and acetate. By terminating cholinergic signaling at nerve–muscle, synaptic, and autonomic synapses, AChE plays a crucial role in fast synaptic transmission and neuromuscular function. It is widely distributed in the nervous system and in non-neuronal tissues, including the neuromuscular junction, brain regions with cholinergic inputs, and erythrocyte membranes.

The enzyme exists in multiple molecular forms arising from alternative splicing and protein association. In humans, major isoforms include a synaptic/tetrameric form (AChE-S, often membrane-associated) and a soluble read-through form (AChE-R). In the central nervous system, AChE can be anchored by scaffolding proteins such as PRiMA to form tetramers. All forms retain the catalytic core responsible for acetylcholine hydrolysis, while their localization differs and influences physiological roles.

The active site features a catalytic triad (commonly serine, histidine, and glutamate) within a deep gorge that contains a peripheral anionic site. Acetylcholine binds in the gorge, is cleaved by the catalytic serine, and the products are choline and acetate. AChE activity is inhibited by organophosphates (nerve agents and many insecticides), which irreversibly phosphorylate the catalytic serine. Reversible inhibitors, including certain drugs such as neostigmine, physostigmine, and pyridostigmine, are used therapeutically in conditions like myasthenia gravis; pralidoxime can restore activity after organophosphate poisoning if given before aging of the enzyme.

Clinical relevance: measuring AChE activity is important in diagnosing and guiding treatment for cholinergic disorders and poisoning, and its inhibitors have both therapeutic and toxicological significance. The gene encoding the enzyme is ACHE.