cholinesterase

コリンエステラーゼ 　

WordNet

1. an enzyme that hydrolyses acetylcholine (into choline and acetic acid)
2. a medicine that inhibits cholinesterase by combining with it and so has a cholinergic effect

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/12/15 21:31:06」(JST)

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acetylcholinesterase (Yt blood group)
Diagram of Pacific electric ray acetylcholinesterase. From PDB 1EA5.
Identifiers
Symbol	ACHE
Alt. symbols	YT
Entrez	43
HUGO	108
OMIM	100740
RefSeq	NM_015831
UniProt	P22303
Other data
Locus	Chr. 7 q22

butyrylcholinesterase
Cartoon diagram of human butyrylcholinesterase. From PDB 1P0I.
Identifiers
Symbol	BCHE
Alt. symbols	CHE1
Entrez	590
HUGO	983
OMIM	177400
RefSeq	NM_000055
UniProt	P06276
Other data
Locus	Chr. 3 q26.1-26.2

In biochemistry, cholinesterase is a family of enzymes that 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.

Types

There are two types:

• Acetylcholinesterase (EC 3.1.1.7) (AChE), also known as RBC cholinesterase, erythrocyte cholinesterase, or (most formally) acetylcholine acetylhydrolase, found primarily in the blood on red blood cell membranes, in neuromuscular junctions, and in 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.

• Pseudocholinesterase (EC 3.1.1.8) (BChE or BuChE), also known as plasma cholinesterase, butyrylcholinesterase, or (most formally) acylcholine acylhydrolase, is produced in the liver and found primarily in plasma.

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 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.

History

In 1968, Walo Leuzinger et al. successfully purified and crystallized the enzyme from electric eels at Columbia University, NY.

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

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. This is a silent condition that manifests itself only when people that have the deficiency receive the muscle relaxants succinylcholine or 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 pseudocholinesterase was observed in 90.5% cases of acute myocardial infarction.

The presence of acetylcholinesterase in the amniotic fluid may be tested in early pregnancy. A sample of amniotic fluid is removed by amniocentesis, and presence of AChE can confirm several common types of birth defect, including abdominal wall defects and neural tube defects.

Butyrylcholinesterase 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 neurotoxins, 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 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 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.

Some benzodiazepines, e.g. temazepam have an inhibitory effect on cholinesterase.

Outside of biochemical warfare, anticholinesterases are also used for reversing medication induced paralysis during anesthesia; as well as in the treatment of myasthenia gravis, glaucoma, and Alzheimer's disease. Such compounds are used for killing insects in a range of products including sheep dip, organophosphate pesticides, and carbamate 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 of Law and Order: SVU, Olivia Benson is taken to the hospital after being exposed to organophosphates, where she is told her cholinesterase level is low.
• In the film The I Inside, Simon Cable is poisoned with cholinesterase inhibitors and he is given atropine and pralidoxime to help reverse the poison. The doctor is also shown dispensing a diazepam at the beginning of the movie.
• In the film The Rock, Dr. Goodspeed (Nicolas Cage) describes the effects of the chemical weapon VX gas as a cholinesterase inhibitor to John Mason (Sean Connery) 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 Inhibition"

Additional images

• Acetylcholine

• Choline

• Acetic acid

• Butyrylcholine

References

External links

• ATSDR Case Studies in Environmental Medicine: Cholinesterase Inhibitors, Including Insecticides and Chemical Warfare Nerve Agents U.S. Department of Health and Human Services
• Movies at weizmann.ac.il showing the structure of acetylcholinesterase and interactions with various inhibitors.
• Proteopedia Acetylcholinesterase
• PDB Molecule of the Month pdb54_1
• Acetylcholinesterase at the US National Library of Medicine Medical Subject Headings (MeSH)
• Pseudocholinesterase at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

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• 1. 認知症治療におけるコリンエステラーゼ阻害剤 cholinesterase inhibitors in the treatment of dementia
• 2. 認知症の治療 treatment of dementia
• 3. 有機リン剤およびカルバメート中毒 organophosphate and carbamate poisoning
• 4. レビー小体型認知症の予後および治療 prognosis and treatment of dementia with lewy bodies
• 5. 成人における 多発性硬化症の症状のマネージメント symptom management of multiple sclerosis in adults

English Journal

• The therapeutic potential of berberine against the altered intrinsic properties of the CA1 neurons induced by Aβ neurotoxicity.

• Haghani M1, Shabani M2, Tondar M3.
• European journal of pharmacology.Eur J Pharmacol.2015 Jul 5;758:82-8. doi: 10.1016/j.ejphar.2015.03.016. Epub 2015 Apr 8.
• It was demonstrated that treatment with beta amyloid (Aβ) led to extreme alterations in the intrinsic electrophysiological properties of CA1 pyramidal neurons. Also, malfunction of the cholinergic system is correlated to the memory and cognitive impairments. Several new studies have suggested that
• PMID 25861937

• Sperm exposure to carbon-based nanomaterials causes abnormalities in early development of purple sea urchin (Paracentrotus lividus).

• Mesarič T1, Sepčić K1, Drobne D2, Makovec D3, Faimali M4, Morgana S4, Falugi C5, Gambardella C6.
• Aquatic toxicology (Amsterdam, Netherlands).Aquat Toxicol.2015 Jun;163:158-66. doi: 10.1016/j.aquatox.2015.04.012. Epub 2015 Apr 11.
• We examined egg fertilisation in purple sea urchin (Paracentrotus lividus) after sperm exposure to carbon-based nanomaterials, carbon black (CB) and graphene oxide (GO), from 0.0001mg/L to 1.0mg/L. Gastrula stage embryos were investigated for acetylcholinesterase and propionylcholinesterase activiti
• PMID 25897690

• High surface adsorption properties of carbon-based nanomaterials are responsible for mortality, swimming inhibition, and biochemical responses in Artemia salina larvae.

• Mesarič T1, Gambardella C2, Milivojević T3, Faimali M4, Drobne D5, Falugi C6, Makovec D7, Jemec A8, Sepčić K9.
• Aquatic toxicology (Amsterdam, Netherlands).Aquat Toxicol.2015 Jun;163:121-9. doi: 10.1016/j.aquatox.2015.03.014. Epub 2015 Mar 19.
• We investigated the effects of three different carbon-based nanomaterials on brine shrimp (Artemia salina) larvae. The larvae were exposed to different concentrations of carbon black, graphene oxide, and multiwall carbon nanotubes for 48h, and observed using phase contrast and scanning electron micr
• PMID 25889088

Japanese Journal

• Acute Toxicity and Neurobehavioral Effects of Diphenhydramine in Chicks

• Mohammad Fouad K.,Mousa Yaareb J.,Hasan Mohammad M.
• Journal of poultry science 49(1), 51-56, 2012-01
• NAID 40019140968

• 内視鏡的食道静脈瘤硬化療法後の血清コリンエステラーゼ活性上昇に関する検討

• 仲地 健一郎,曽 絵里子,大久保 政雄 [他]
• 肝臓 52(12), 784-786, 2011-12
• NAID 40019127066

Related Links

• Cholinesteraseとは - goo Wikipedia (ウィキペディア)

Cholinesteraseとは？goo Wikipedia (ウィキペディア) 。出典：Wikipedia（ウィキペディア）フリー百科事典。 Cholinesteraseとは - goo Wikipedia (ウィキペディア) gooトップ サイトマップ スタートページに設定 RSS ヘルプ メニューへスキップ ...

• Cholinesterase | Define Cholinesterase at Dictionary.com

Cholinesterase definition, an enzyme, found especially in the heart, brain, and blood, that hydrolyzes acetylcholine to acetic acid and choline. See more. Thesaurus Translate Puzzles & Games Word of the Day Blog Slideshows ...

Related Pictures

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★リンクテーブル★

リンク元	「コリンエステラーゼ」「ChE」
拡張検索	「anticholinesterase agent」「cholinesterase inhibitor」「acetylcholinesterase」「red blood cell cholinesterase」「plasma cholinesterase」
関連記事	「cholinesterases」

「コリンエステラーゼ」

　　[★]

英

cholinesterase, ChE

概念

• コリンエステラーゼはコリンエステルをコリンと有機酸に加水分解する酵素(LAB.601)
• 血清中のコリンエステラーゼは、アセチルコリン、ブチルコリン、ベンゾイルコリンなどのコリンエステルや、α-ナフチル酢酸などの非コリン性エステルも加水分解する(LAB.601)

• 血清中のコリンエステラーゼは偽性コリンエステラーゼ pseudocholinesterase、血清コリンエステラーゼ serum cholinesterase、非特異的コリンエステラーゼ non-specific cholinesterase、アシルコリンエステラーゼ acylcholine esteraseとも呼ばれる

阻害薬

可逆的阻害薬 カルバミン酸誘導体

• フィゾスチグミン　☆
• ネオスチグミン　☆
• エドロフォニウム

不可逆的阻害薬 有機リン製剤

• 有機リン系農薬

• パラチオン、マラソン、スミチオン、サリン

不可逆的阻害薬により不活性化されたChEの賦活化

• PAM

コリンエステラーゼの比較 (SPC.157)

		主な存在部位	主な機能	基質特異性
				アセチルコリン	カルバコール	アセチル-β-メチルコリン	ブチリルコリン
アセチルコリンエステラーゼ	AchE	脳、コリン作動性シナプス	AChをコリンと酢酸に分解	+	-	+	-
偽コリンエステラーゼ	pseudo-ChE (=BuChE)	血清、肝臓	健康診断の指標 低値：肝硬変・肝炎・有機リン系農薬中毒	+	-	-	+

「ChE」

　　[★] コリンエステラーゼ cholinesterase

「anticholinesterase agent」

　　[★]

• 抗コリンエステラーゼ薬、抗コリンエステラーゼ剤

関

acetylcholinesterase inhibitor、anticholinesterase、cholinesterase inhibitor

「cholinesterase inhibitor」

　　[★] コリンエステラーゼ阻害薬

関

acetylcholinesterase inhibitor、anticholinesterase、anticholinesterase agent

「acetylcholinesterase」

　　[★] アセチルコリンエステラーゼ AChE

「red blood cell cholinesterase」

　　[★]

赤血球コリンエステラーゼ

「plasma cholinesterase」

　　[★]

• 血漿コリンエステラーゼ

「cholinesterases」

　　[★] コリンエステラーゼ