Acetylcholinesterase (1) Sites of location  Cholinergic neurons  Cholinergic synapses  Neuromuscular junction  Red blood cells Substrates  Acetylcholine is the best substrate  Methacholine is a substrate  Hydrolyzes ACh at greater velocity than choline esters with acyl groups larger than acetate or proprionate

Acetylcholinesterase (2) Esters that are not substrates  Bethanechol  Carbachol  Succinylcholine Its inhibition produces synergistic interaction with methacholine and additive actions with bethanechol and carbachol Drugs that block its hydrolysis of esters are called cholinesterase inhibitors

Drug Interactions of Choline Esters and Inhibitors of Acetylcholinesterase - Synergism versus Additivity Methacholine Carbachol Bethanechol

Butyrylcholinesterase (Plasma esterase, pseudocholinesterase, serum esterase, BuChE, PseudoChE)

Butyrylcholinesterase (1) Sites of location  Plasma, liver, glial cells, other tissues Substrates  Butyrylcholine is the best  Acetylcholine  Succinylcholine  Procaine

Butyrylcholinesterase (2) Esters that are not substrates  Methacholine, bethanechol, and carbachol Is inhibited by carbamyl and organophosphate inhibitors of acetylcholinesterase

Active Site of Acetylcholinesterase

Interaction of AChE and Acetylcholine

Acetylation of AChE and Release of Choline

Hydroxyl Group of Water Attacks the Carbonyl Group of Acetylated- AChE to Liberate AChE

Carbamyl Inhibitors of AChE