Acetylcholinesterase and butyrylcholinesterase (AChE and BChE)

Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are closely related enzymes that catalyze the hydrolysis of acetylcholine and butyrylcholine, respectively, both belonging to the serine hydrolase and carboxylesterase enzyme superfamilies[3][5]. AChE is primarily found in neuromuscular junctions and cholinergic synapses, where it rapidly terminates synaptic transmission by hydrolyzing acetylcholine, thus ensuring precise control of neural signaling[3][1]. BChE, though structurally similar, is distributed more broadly in the body, with less defined endogenous roles but is important for hydrolysis and detoxification of a wider range of ester-containing drugs and toxins and acts as a backup for AChE[5][6]. Both enzymes are major targets in neurodegenerative disorder therapy, especially Alzheimer’s disease: their selective inhibition increases central acetylcholine, improving cognitive symptoms[2][4][6]. Irreversible poisoning of these enzymes is central to the action of nerve agents, pesticides, and some drugs. Plasma BChE is used as a biomarker in various disease states, and genetic polymorphisms in BChE significantly affect individual drug responses. Safety concerns primarily relate to systemic cholinergic excess and the fine balance required for effective yet safe enzyme inhibition. Both enzymes remain highly relevant for clinical pharmacology, toxicology, and neurological disease management[2][8][6].

Other names

Acetylcholine acetylhydrolase (AChE)Butyrylcholine esterase (BChE)CholinesterasesAcetylhydrolaseAcetylcholine-esteraseCholine esterase I (for AChE)Pseudocholinesterase (for BChE)

Competitive or non-competitive inhibition of the active site gorge—blockade of acetylcholine or butyrylcholine hydrolysis Covalent modification by carbamates or organophosphates leading to irreversible inhibition Donepezil, rivastigmine, and galantamine are reversible inhibitors increasing synaptic acetylcholine Some drugs are dual AChE/BChE inhibitors, while others are selective