Acetylcholinesterase

In biochemistry, cholinesterase is a term which refers to one of the two enzymes:
 * Acetylcholinesterase (AChE), also known as RBC cholinesterase, erythrocyte cholinesterase, or (most formally) acetylcholine acetylhydrolase, found primarily in the blood and neural synapses
 * Pseudocholinesterase (BChE or BuChE), also known as plasma cholinesterase, butyrylcholinesterase, or (most formally) acylcholine acylhydrolase, found primarily in the liver

Both of these compounds catalyze the hydrolysis of the neurotransmitter acetylcholine into choline and acetic acid, a reaction necessary to allow a cholinergic neuron to return to its resting state after activation.

The difference between the two types of cholinesterase has to do with their respective preferences for substrates: the former hydrolyses acetylcholine more quickly; the latter hydrolyses butyrylcholine less quickly. In 1968, Walo Leuzinger et al successfully purified and cristalyzed the enzyme from electric eels at Columbia University, NY. The 3D structure of acetylcholinesterase was first determined in 1991 by Sussman et al using protein from the Pacific electric ray.

An absence or mutation of the pseudocholinesterase enzyme leads to a medical condition known simply as pseudocholinesterase deficiency. This is a silent condition that only manifests itself when people who have the deficiency receive the muscle relaxants succinylcholine or mivacurium during a surgery.

Cholinesterase inhibitors
A cholinesterase inhibitor (or "anticholinesterase") suppresses the action of the enzyme. Because of its essential function, chemicals that interfere with the action of cholinesterase are potent neurotoxins, causing excessive salivation and eye watering in low doses, followed by muscle spasms and ultimately death (examples are snake venom, sarin and VX).

One of the most common classes of acetylcholinesterase inhibitors are phosphorus-based compounds which are designed to bind to the active site of the enzyme. The structural requirements are a phosphorus atom bearing two lipophilic groups, a leaving group (such as a halide or thiocyanate) and a terminal oxygen. The entry on Lawesson's reagent has some details on one sub-class of the phosphorus-based compounds.

Outside of biochemical warfare, anticholinesterases are also used in anesthesia or in the treatment of myasthenia gravis, glaucoma and Alzheimer's disease. Also such compounds are used for killing insects in a range of products including sheep dip. In addition to acute poisoning as described above, a semi-acute poisoning characterized by strong mental disturbances can occur.

Reference

 * Sussman JL, Harel M, Frolow F, Oefner C, Goldman A, Toker L, Silman I. Atomic structure of acetylcholinesterase from Torpedo californica: a prototypic acetylcholine-binding protein. Science 1991;253:872-9. PMID 1678899.