Choline acetyltransferase (ChAT)

Choline acetyltransferase (ChAT) is an enzyme responsible for catalyzing the transfer of an acetyl group from acetyl-coenzyme A to choline, producing the neurotransmitter acetylcholine. ChAT is a defining marker of cholinergic neurons and is essential for the function and maintenance of cholinergic systems in both the central and peripheral nervous system. The enzyme is a single-chain globular protein, expressed in neurons and some other cell types, and exists in soluble and membrane-associated forms. Genetically, mutations in the ChAT gene can cause congenital myasthenic syndromes due to disruption in acetylcholine production. Decreased ChAT activity or expression is closely associated with neurodegenerative diseases, notably Alzheimer’s disease. Although ChAT itself has been identified as a potential drug target and experimental inhibitors exist, current therapies for cholinergic dysfunction rely on cholinesterase inhibitors, which act downstream by preventing acetylcholine breakdown rather than directly targeting ChAT. The crystal structures of ChAT reveal a two-domain monomer with the active site located in a solvent-accessible tunnel at the domain interface, facilitating substrate binding and catalysis.

Other names

ChATCholine-O-acetyltransferaseEC 2.3.1.6

Competitive enzyme inhibition (for AVP derivatives and similar ChAT inhibitors); Not typically a direct drug target; most drug interventions modulate acetylcholine levels by inhibiting downstream degradation, not ChAT itself