AChE

Acetylcholinesterase (AChE) is a serine hydrolase that rapidly hydrolyzes the neurotransmitter acetylcholine into choline and acetate at cholinergic synapses, thereby terminating the synaptic signal. In humans, the Ache gene encodes the AChE protein. It is abundant in nervous system tissues, particularly at neuromuscular junctions and in brain interneuronal synapses, as well as in red blood cells and other tissues.

Mechanism: AChE features a catalytic triad and an anionic subsite within a deep active-site gorge. The enzyme catalyzes an acylation step on the serine residue followed by deacylation, enabling fast turnover (often millions of cycles per minute). The quaternary ammonium of acetylcholine binds in the anionic subsite, ensuring high specificity.

Molecular forms and localization: AChE exists in several molecular forms produced by alternative splicing and post-translational assembly, including soluble dimers and tetramers that associate with a collagen-like tail to anchor at membranes. At cholinergic synapses, AChE concentrates in the synaptic basal lamina and postsynaptic membranes, ensuring rapid acetylcholine clearance after release.

Clinical and pharmacological relevance: AChE is a target of organophosphates (pesticides, nerve agents) and carbamates, which inhibit hydrolysis and cause accumulation of acetylcholine and cholinergic toxicity. Treatments for organophosphate poisoning include atropine (a muscarinic antagonist) and oximes such as pralidoxime to reactivate the enzyme. AChE inhibitors are also used therapeutically to treat Alzheimer's disease by increasing brain acetylcholine levels, for example donepezil, rivastigmine, and galantamine. AChE activity is commonly assessed in clinical laboratories to evaluate exposure or disease.