Cholinesterase

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Not to be confused with Acetylcholinesterase.
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The enzyme cholinesterase (EC 3.1.1.8, choline esterase; systematic name acylcholine acylhydrolase) catalyses the hydrolysis of choline-based esters:

an acylcholine + H2O = choline + a carboxylate

Several of these serve as

catalyze the hydrolysis of these cholinergic neurotransmitters, such as breaking acetylcholine into choline and acetic acid.[1] These reactions are necessary to allow a cholinergic neuron to return to its resting state after activation. For example, in muscle contraction, acetylcholine at a neuromuscular junction triggers a contraction; but for the muscle to relax afterward, rather than remaining locked in a tense state, the acetylcholine must be broken down by a choline esterase. The main type for that purpose is acetylcholinesterase (also called choline esterase I[2] or erythrocyte cholinesterase); it is found mainly in chemical synapses and red blood cell membranes. The other type is butyrylcholinesterase (also called choline esterase II[2] or plasma cholinesterase); it is found mainly in the blood plasma
.

Types and nomenclature

The two types of cholinesterase are

substrates: the former hydrolyses acetylcholine more quickly; the latter hydrolyses butyrylcholine
more quickly.

The term cholinesterase is sometimes used to refer specifically to butyrylcholinesterase,

usage produces the oddity that cholinesterase and false cholinesterase (pseudocholinesterase) under that scheme mean the same thing[2] (confusingly), and acetylcholinesterase is then called true cholinesterase in contrast,[2] producing the second oddity that cholinesterase and true cholinesterase then do not mean the same thing. But such usage is now outdated; the current, unambiguous HGNC
names and symbols are acetylcholinesterase (ACHE) and butyrylcholinesterase (BCHE).

Acetylcholinesterase (EC 3.1.1.7) (ACHE), also known as AChE, choline esterase I, RBC cholinesterase, or erythrocyte cholinesterase, true cholinesterase, choline esterase I, or (most formally) acetylcholine acetylhydrolase, is found primarily in the blood on red blood cell membranes, in neuromuscular junctions, and in other neural synapses. Acetylcholinesterase exists in multiple molecular forms. In the mammalian brain the majority of AChE occurs as a tetrameric, G4 form (10) with much smaller amounts of a monomeric G1 (4S) form.[3]

Butyrylcholinesterase (

butyl and butyryl syllables both refer to butane with one of its terminal methyl groups
substituted.

The half-life of BCHE is approximately 10 to 14 days.

succinylcholine.[5][6]

Discovery

In 1968, Walo Leuzinger et al. successfully purified and crystallized acetylcholinesterase from electric eels at Columbia University, New York.[7][8]

The 3D structure of acetylcholinesterase was first determined in 1991 by Joel Sussman et al. using protein from the Pacific electric ray.[9]

Clinically useful quantities of butyrylcholinesterase were synthesized in 2007 by PharmAthene, through the use of genetically modified goats.[10]

Clinical significance

An absence or mutation of the BCHE enzyme leads to a medical condition known as

mivacurium
during a surgery.

Pseudocholinesterase deficiency may also affect local anaesthetic selection in dental procedures. The enzyme plays an important role in the metabolism of ester-based local anaesthetics, a deficiency lowers the margin of safety and increases the risk of systemic effects with this type of anaesthetic. The selection of an amide-based solution is recommended in such patients.

Elevation of plasma BCHE levels was observed in 90.5% of cases of acute myocardial infarction.[11]

The presence of ACHE in the amniotic fluid may be tested in early pregnancy. A sample of amniotic fluid is removed by

neural tube defects.[12]

BCHE can be used as a

nerve gas and other organophosphate poisoning.[10]

Some early research points to genetic butylcholinesterase deficiency as a possible candidate component in

sudden infant death syndrome.[13]

The enzyme Acetylcholin esterase, and its inhibition, plays a role in the development of myofascial trigger points and the associated myofascial pain syndrome. By injecting a mouse with acetylcholin esterase inhibitors and electrical stimulation, the muscle develops trigger points.[14][15]

Inhibitors

A

snake venoms, and the nerve gases sarin and VX). One counteracting medication is pralidoxime
. The so-called nerve gases and many substances used in insecticides have been shown to act by combining with a residue of serine in the active site of acetylcholine esterase, inhibiting the enzyme completely. The enzyme acetylcholine esterase breaks down the neurotransmitter acetylcholine, which is released at nerve and muscle junctions, in order to allow the muscle or organ to relax. The result of acetylcholine esterase inhibition is that acetylcholine builds up and continues to act so that any nerve impulses are continually transmitted and muscle contractions do not stop.

Among the most common acetylcholinesterase inhibitors are phosphorus-based compounds, which are designed to bind to the active site of the

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.

Some

benzodiazepines, e.g., temazepam have an inhibitory effect on cholinesterase.[16]

Cholinesterase levels can be used as an indirect marker of arsenic exposure.[17]

Outside of

birth defects.[citation needed
]

Additional images

References

  1. ^
    PMID 24179466
    .
  2. ^ a b c d e Elsevier, Dorland's Illustrated Medical Dictionary, Elsevier, archived from the original on 2014-01-11, retrieved 2015-09-24.
  3. PMID 15956816
    .
  4. S2CID 32806785
    .
  5. ISBN 978-0-7817-5745-4
    .
  6. ISBN 978-0-443-06618-4
    .
  7. PMID 16591490
    .
  8. PMID 5238989
    .
  9. S2CID 28833513
    .
  10. ^
    PMID 17660298
    .
  11. ISBN 978-93-5025-484-4
    .
  12. ^ FBR Resource Guide: Acetylcholinesterase-Amniotic Fluid Archived 2007-06-25 at the Wayback Machine. Foundation for Blood Research (September 7, 2007). Retrieved on 2007-11-21.
  13. PMID 35533499
    .
  14. S2CID 1829156
    . Retrieved 2023-09-24.
  15. PMID 14759755
    .
  16. PMID 29327
    .
  17. PMID 20618979
    .

External links