In biochemistry
Biochemistry, sometimes called biological chemistry, is the study of chemical processes in living organisms, including, but not limited to, living matter. Biochemistry governs all living organisms and living processes...

, cholinesterase is a family of enzymes that catalyze the hydrolysis
Hydrolysis is a chemical reaction during which molecules of water are split into hydrogen cations and hydroxide anions in the process of a chemical mechanism. It is the type of reaction that is used to break down certain polymers, especially those made by condensation polymerization...

 of the neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...

The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...

 into choline
Choline is a water-soluble essential nutrient. It is usually grouped within the B-complex vitamins. Choline generally refers to the various quaternary ammonium salts containing the N,N,N-trimethylethanolammonium cation....

 and acetic acid
Acetic acid
Acetic acid is an organic compound with the chemical formula CH3CO2H . It is a colourless liquid that when undiluted is also called glacial acetic acid. Acetic acid is the main component of vinegar , and has a distinctive sour taste and pungent smell...

, a reaction necessary to allow a cholinergic
The word choline generally refers to the various quaternary ammonium salts containing the N,N,N-trimethylethanolammonium cation. Found in most animal tissues, choline is a primary component of the neurotransmitter acetylcholine and functions with inositol as a basic constituent of lecithin...

 neuron to return to its resting state after activation.


There are two types:
  • Acetylcholinesterase
    "Acetylcholinesterase, also known as AChE or acetylcholine acetylhydrolase, is an enzyme that degrades the neurotransmitter acetylcholine, producing choline and an acetate group. It is mainly found at neuromuscular junctions and cholinergic nervous system, where its activity serves to terminate...

    (AChE), also known as RBC
    Red blood cell
    Red blood cells are the most common type of blood cell and the vertebrate organism's principal means of delivering oxygen to the body tissues via the blood flow through the circulatory system...

    , erythrocyte cholinesterase, or (most formally) acetylcholine acetylhydrolase, found primarily in the blood
    Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....

     and neural synapse
    In the nervous system, a synapse is a structure that permits a neuron to pass an electrical or chemical signal to another cell...

    s. 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.

  • Pseudocholinesterase
    Butyrylcholinesterase is a non-specific cholinesterase enzyme that hydrolyses many different choline esters...

    (BChE or BuChE), also known as plasma cholinesterase, butyrylcholinesterase, or (most formally) acylcholine acylhydrolase, found primarily in the liver
    The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...


The difference between the two types of cholinesterase has to do with their respective preferences for substrate
Substrate (biochemistry)
In biochemistry, a substrate is a molecule upon which an enzyme acts. Enzymes catalyze chemical reactions involving the substrate. In the case of a single substrate, the substrate binds with the enzyme active site, and an enzyme-substrate complex is formed. The substrate is transformed into one or...

s: the former hydrolyses acetylcholine more quickly; the latter hydrolyses butyrylcholine
Butyrylcholine is an acetylcholine-like molecule, with activation of some of the same receptors as acetylcholine. It is hydrolysed by acetylcholinesterase and butyrylcholinesterase , with butyrylcholinesterase being more efficient than acetylcholinesterase.Butyrylcholine is a synthetic compound and...

 more quickly.

The half-life of pseudocholinesterase is approximately 8–16 hours. Pseudocholinesterase levels may be reduced in patients with advanced liver disease. The decrease must be greater than 75% before significant prolongation of neuromuscular blockade occurs with succinylcholine.


In 1968, Walo Leuzinger et al. successfully purified and crystallized the enzyme from electric eel
Electric eel
The electric eel , is an electric fish, and the only species of the genus Electrophorus. It is capable of generating powerful electric shocks, of up to six hundred volts, which it uses for both hunting and self-defense. It is an apex predator in its South American range...

s at Columbia University, NY.

The 3D structure of acetylcholinesterase was first determined in 1991 by Joel Sussman
Joel Sussman
Joel L. Sussman is an Israeli crystallographer best known for his studies on acetylcholinesterase, a key protein involved in transmission of nerve signals...

 et al. using protein from the Pacific electric ray
Pacific electric ray
The Pacific electric ray is a species of electric ray in the family Torpedinidae, endemic to the coastal waters of the northeastern Pacific Ocean from Baja California to British Columbia. It generally inhabits sandy flats, rocky reefs, and kelp forests from the surface to a depth of , but has also...


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

Clinical significance

An absence or mutation of the pseudocholinesterase enzyme leads to a medical condition known as pseudocholinesterase deficiency
Pseudocholinesterase deficiency
Pseudocholinesterase deficiency is an inherited blood plasma enzyme abnormality. People who have this abnormality may be sensitive to certain anesthetic drugs, including the muscle relaxants succinylcholine and mivacurium as well as other ester local anesthetics...

. This is a silent condition that manifests itself only when people that have the deficiency receive the muscle relaxants succinylcholine or mivacurium
Mivacurium chloride is a short-duration non-depolarizing neuromuscular-blocking drug or skeletal muscle relaxant in the category of non-depolarizing neuromuscular-blocking drugs, used adjunctively in anesthesia to facilitate endotracheal intubation and to provide skeletal muscle relaxation during...

 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 pseudocholinesterase was observed in 90.5% cases of acute myocardial infarction
Myocardial infarction
Myocardial infarction or acute myocardial infarction , commonly known as a heart attack, results from the interruption of blood supply to a part of the heart, causing heart cells to die...


The presence of acetylcholinesterase in the amniotic fluid may be tested in early pregnancy. A sample of amniotic fluid is removed by amniocentesis
Amniocentesis is a medical procedure used in prenatal diagnosis of chromosomal abnormalities and fetal infections, in which a small amount of amniotic fluid, which contains fetal tissues, is sampled from the amnion or amniotic sac surrounding a developing fetus, and the fetal DNA is examined for...

, and presence of AChE can confirm several common types of birth defect, including abdominal wall defects and neural tube defects
Neural tube defects
Neural tube defects are one of the most common birth defects, occurring in approximately one in 1,000 live births in the United States. An NTD is an opening in the spinal cord or brain that occurs very early in human development. In the 2nd week of pregnancy called gastrulation, specialized cells...


Butyrylcholinesterase is a non-specific cholinesterase enzyme that hydrolyses many different choline esters...

 can be used as a prophylactic agent against nerve gas and other organophosphate poisoning.

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 neurotoxin
A neurotoxin is a toxin that acts specifically on nerve cells , usually by interacting with membrane proteins such as ion channels. Some sources are more general, and define the effect of neurotoxins as occurring at nerve tissue...

s, causing excessive salivation and eye-watering in low doses, followed by muscle spasms and ultimately death (examples are some snake venoms, and the nerve gases sarin
Sarin, or GB, is an organophosphorus compound with the formula [2CHO]CH3PF. It is a colorless, odorless liquid, which is used as a chemical weapon. It has been classified as a weapon of mass destruction in UN Resolution 687...

 and VX
VX (nerve agent)
VX, IUPAC name O-ethyl S-[2-ethyl] methylphosphonothioate, is an extremely toxic substance whose only application is in chemical warfare as a nerve agent. As a chemical weapon, it is classified as a weapon of mass destruction by the United Nations in UN Resolution 687...

). One counteracting medication is pralidoxime
Pralidoxime or 2-PAM, usually as the chloride or methiodide salts, belongs to a family of compounds called oximes that bind to organophosphate-inactivated acetylcholinesterase. It is used to combat poisoning by organophosphates or acetylcholinesterase inhibitors , in conjunction with atropine and ...

. 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 enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

. The structural requirements are a phosphorus
Phosphorus is the chemical element that has the symbol P and atomic number 15. A multivalent nonmetal of the nitrogen group, phosphorus as a mineral is almost always present in its maximally oxidized state, as inorganic phosphate rocks...

 atom bearing two lipophilic
Lipophilicity, , refers to the ability of a chemical compound to dissolve in fats, oils, lipids, and non-polar solvents such as hexane or toluene. These non-polar solvents are themselves lipophilic — the axiom that like dissolves like generally holds true...

 groups, a leaving group (such as a halide
A halide is a binary compound, of which one part is a halogen atom and the other part is an element or radical that is less electronegative than the halogen, to make a fluoride, chloride, bromide, iodide, or astatide compound. Many salts are halides...

 or thiocyanate
Thiocyanate is the anion [SCN]−. It is the conjugate base of thiocyanic acid. Common derivatives include the colourless salts potassium thiocyanate and sodium thiocyanate. Organic compounds containing the functional group SCN are also called thiocyanates...

), and a terminal
A polymer is a large molecule composed of repeating structural units. These subunits are typically connected by covalent chemical bonds...

Oxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...

. The entry on Lawesson's reagent
Lawesson's reagent
Lawesson's reagent, or LR, is a chemical compound used in organic synthesis as a thiation agent. Lawesson's reagent was first made popular by Sven-Olov Lawesson, who did not, however, invent it. Lawesson's reagent was first made in 1956 during a systematic study of the reactions of arenes with...

 has some details on one sub-class of the phosphorus-based compounds.

Some benzodiazepines, e.g. temazepam
Temazepam is an intermediate-acting 3-hydroxy benzodiazepine. It is mostly prescribed for the short-term treatment of sleeplessness in patients who have difficulty maintaining sleep...

 have an inhibitory effect on cholinesterase.

Outside of biochemical warfare, anticholinesterases are also used for reversing medication induced paralysis during anesthesia
Anesthesia, or anaesthesia , traditionally meant the condition of having sensation blocked or temporarily taken away...

; as well as in the treatment of myasthenia gravis
Myasthenia gravis
Myasthenia gravis is an autoimmune neuromuscular disease leading to fluctuating muscle weakness and fatiguability...

, glaucoma
Glaucoma is an eye disorder in which the optic nerve suffers damage, permanently damaging vision in the affected eye and progressing to complete blindness if untreated. It is often, but not always, associated with increased pressure of the fluid in the eye...

, and Alzheimer's disease
Alzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...

. Such compounds are used for killing insects in a range of products including sheep dip
Sheep dip
Sheep dip is a liquid formulation of insecticide and fungicide which shepherds and farmers may use to protect their sheep from infestation against external parasites such as itch mite , blow-fly, ticks and lice...

, organophosphate
An organophosphate is the general name for esters of phosphoric acid. Phosphates are probably the most pervasive organophosphorus compounds. Many of the most important biochemicals are organophosphates, including DNA and RNA as well as many cofactors that are essential for life...

 pesticides, and carbamate
Carbamates are organic compounds derived from carbamic acid . A carbamate group, carbamate ester, and carbamic acids are functional groups that are inter-related structurally and often are interconverted chemically. Carbamate esters are also called urethanes.-Synthesis:Carbamic acids are derived...

 pesticides. In addition to acute poisoning as described above, a semi-acute poisoning characterized by strong mental disturbances can occur. Also, prolonged exposure can cause birth defects.

Pop culture

  • On season eight
    Law & Order: Special Victims Unit (season 8)
    This article contains a list of episodes for season 8 of the television series, Law & Order: Special Victims Unit.-Cast:*Christopher Meloni as Det. Elliot Stabler*Mariska Hargitay as Det. Olivia Benson*Richard Belzer as Det. John Munch...

     of Law and Order: SVU, Olivia Benson
    Olivia Benson
    Det. Olivia "Liv" Benson is a fictional character on the NBC police procedural drama Law & Order: Special Victims Unit, portrayed by Mariska Hargitay. She is the former partner of Elliot Stabler. In Season 13, her partner will be Nick Amaro...

     is taken to the hospital
    A hospital is a health care institution providing patient treatment by specialized staff and equipment. Hospitals often, but not always, provide for inpatient care or longer-term patient stays....

     after being exposed to organophosphates, where she is told her cholinesterase level is low.
  • In the film The I Inside
    The i Inside
    The I Inside is a 2003 psychological thriller directed by Roland Suso Richter. It was written by Michael Cooney based on his own play Point of Death. This film has no connection with the science-fiction novel, The I Inside, by Alan Dean Foster....

    , Simon Cable is poisoned with cholinesterase inhibitors and he is given atropine
    Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade , Jimson weed , mandrake and other plants of the family Solanaceae. It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects...

     and pralidoxime
    Pralidoxime or 2-PAM, usually as the chloride or methiodide salts, belongs to a family of compounds called oximes that bind to organophosphate-inactivated acetylcholinesterase. It is used to combat poisoning by organophosphates or acetylcholinesterase inhibitors , in conjunction with atropine and ...

     to help reverse the poison. The doctor is also shown dispensing a diazepam
    Diazepam , first marketed as Valium by Hoffmann-La Roche is a benzodiazepine drug. Diazepam is also marketed in Australia as Antenex. It is commonly used for treating anxiety, insomnia, seizures including status epilepticus, muscle spasms , restless legs syndrome, alcohol withdrawal,...

     at the beginning of the movie, which is contraindicated in cholinesterase inhibition.
  • In the film The Rock
    The Rock (film)
    The Rock is a 1996 action film that primarily takes place on Alcatraz Island and in the San Francisco Bay area. It was directed by Michael Bay and stars Sean Connery, Nicolas Cage and Ed Harris. It was produced by Don Simpson and Jerry Bruckheimer and released through Hollywood Pictures. The film...

    , Dr. Goodspeed (Nicolas Cage
    Nicolas Cage
    Nicolas Cage is an American actor, producer and director, having appeared in over 60 films including Raising Arizona , The Rock , Face/Off , Gone in 60 Seconds , Adaptation , National Treasure , Ghost Rider , Bad Lieutenant: Port of Call New Orleans , and...

    ) describes the effects of the chemical weapon VX gas as a cholinesterase inhibitor to John Mason (Sean Connery
    Sean Connery
    Sir Thomas Sean Connery , better known as Sean Connery, is a Scottish actor and producer who has won an Academy Award, two BAFTA Awards and three Golden Globes Sir Thomas Sean Connery (born 25 August 1930), better known as Sean Connery, is a Scottish actor and producer who has won an Academy...

    ) as they remove guidance chips from the rocket designed to deliver the gas into San Francisco from Alcatraz.
  • Indie band Ruet Caelum have a song entitled 'Showing Signs of Cholinesterase Inhabition"

External links

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