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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2017/04/21 15:59:33」(JST)

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Butyrylcholinesterase (HGNC symbol BCHE), also known as BChE, BuChE, pseudocholinesterase, or plasma (cholin)esterase,^[5] is a nonspecific cholinesterase enzyme that hydrolyses many different choline-based esters. In humans, it is made in the liver, found mainly in blood plasma, and encoded by the BCHE gene.^[6]

It is very similar to the neuronal acetylcholinesterase, which is also known as RBC or erythrocyte cholinesterase.^[5] The term "serum cholinesterase" is generally used in reference to a clinical test that reflects levels of both of these enzymes in the blood.^[5] Assay of butyrylcholinesterase activity in plasma can be used as a liver function test as both hypercholinesterasemia and hypocholinesterasemia indicate pathological processes. The half-life of BCHE is approximately 10 to 14 days.^[7]

Butyrylcholine is a synthetic compound that does not occur in the body naturally. It is used as a tool to distinguish between acetylcholinesterase and butyrylcholinesterase.

Clinical significance

Pseudocholinesterase deficiency results in delayed metabolism of only a few compounds of clinical significance, including the following: succinylcholine, mivacurium, procaine, heroin, and cocaine. Of these, its most clinically important substrate is the depolarizing neuromuscular blocking agent, succinylcholine, which the pseudocholinesterase enzyme hydrolyzes to succinylmonocholine and then to succinic acid.

In individuals with normal plasma levels of normally functioning pseudocholinesterase enzyme, hydrolysis and inactivation of approximately 90-95% of an intravenous dose of succinylcholine occurs before it reaches the neuromuscular junction. The remaining 5-10% of the succinylcholine dose acts as an acetylcholine receptor agonist at the neuromuscular junction, causing prolonged depolarization of the postsynaptic junction of the motor-end plate. This depolarization initially triggers fasciculation of skeletal muscle. As a result of prolonged depolarization, endogenous acetylcholine released from the presynaptic membrane of the motor neuron does not produce any additional change in membrane potential after binding to its receptor on the myocyte. Flaccid paralysis of skeletal muscles develops within 1 minute. In normal subjects, skeletal muscle function returns to normal approximately 5 minutes after a single bolus injection of succinylcholine as it passively diffuses away from the neuromuscular junction. Pseudocholinesterase deficiency can result in higher levels of intact succinylcholine molecules reaching receptors in the neuromuscular junction, causing the duration of paralytic effect to continue for as long as 8 hours. This condition is recognized clinically when paralysis of the respiratory and other skeletal muscles fails to spontaneously resolve after succinylcholine is administered as an adjunctive paralytic agent during anesthesia procedures. In such cases respiratory assistance is required.^[8]

In 2008, an experimental new drug was discovered for the potential treatment of cocaine abuse and overdose based on the pseudocholinesterase structure. It was shown to remove cocaine from the body 2000 times as fast as the natural form of BChE. Studies in rats have shown that the drug prevented convulsions and death when administered cocaine overdoses.^[9] This enzyme also metabolizes succinylcholine which accounts for its rapid degradation in the liver and plasma. There may be genetic variability in the kinetics of this enzyme that can lead to prolonged muscle blockade and potentially dangerous respiratory depression that needs to be treated with assisted ventilation.

Mutant alleles at the BCHE locus are responsible for suxamethonium sensitivity. Homozygous persons sustain prolonged apnea after administration of the muscle relaxant suxamethonium in connection with surgical anesthesia. The activity of pseudocholinesterase in the serum is low and its substrate behavior is atypical. In the absence of the relaxant, the homozygote is at no known disadvantage.^[10]

Finally, pseudocholinesterase metabolism of procaine results in formation of paraaminobenzoic acid (PABA). If the patient receiving procaine is on sulfonamide antibiotics such as bactrim the antibiotic effect will be antagonized by providing a new source of PABA to the microbe for subsequent synthesis of folic acid.

Prophylactic countermeasure against nerve gas

Butyrylcholinesterase is a prophylactic countermeasure against organophosphate nerve agents. It binds nerve agent in the bloodstream before it can exert effects in the nervous system. Because it is a biological scavenger (and universal target), it is currently the only therapeutic agent effective in providing complete stoichiometric protection against the entire spectrum of organophosphate nerve agents.^[11]

Physiological role

It was recently indicated that butyrylcholinesterase could be a physiological ghrelin regulator.^[12]

Interactive pathway map

Click on genes, proteins and metabolites below to link to respective articles. ^{[§ 1]}

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|{{{bSize}}}px|alt=Irinotecan Pathway edit]]

File:IrinotecanPathway_WP229.png

Irinotecan Pathway edit

^ The interactive pathway map can be edited at WikiPathways: "IrinotecanPathway_WP46359".

Inhibitors

Cymserine and derivatives
Profenamine
Rivastigmine
Tacrine
(+)-ZINC-12613047: IC₅₀ human BChE 13nM, high selectivity over AChE.^[13]

Nomenclature

The nomenclatural variations of BCHE and of cholinesterases generally are discussed at Cholinesterase § Types and nomenclature.

References

^ "Diseases that are genetically associated with BCHE view/edit references on wikidata".
^ "Drugs that physically interact with Butyrylcholinesterase view/edit references on wikidata".
^ "Human PubMed Reference:".
^ "Mouse PubMed Reference:".
^ ^a ^b ^c Jasmin L (2013-05-28). "Cholinesterase - blood". University of Maryland Medical Center.
^ Allderdice PW, Gardner HA, Galutira D, Lockridge O, LaDu BN, McAlpine PJ (Oct 1991). "The cloned butyrylcholinesterase (BCHE) gene maps to a single chromosome site, 3q26". Genomics. 11 (2): 452–4. doi:10.1016/0888-7543(91)90154-7. PMID 1769657.
^ Whittaker M (1980). "Plasma cholinesterase variants and the anaesthetist". Anaesthesia. 35 (2): 174–197. doi:10.1111/j.1365-2044.1980.tb03800.x. PMID 6992635.
^ "Pseudocholinesterase Deficiency". Medscape. WebMD LLC.
^ Zheng F, Yang W, Ko MC, Liu J, Cho H, Gao D, Tong M, Tai HH, Woods JH, Zhan CG (Sep 2008). "Most efficient cocaine hydrolase designed by virtual screening of transition states". Journal of the American Chemical Society. 130 (36): 12148–55. doi:10.1021/ja803646t. PMC 2646118. PMID 18710224. Lay summary – ScienceDaily.
^ "Entrez Gene: BCHE butyrylcholinesterase".
^ "Medical Identification and Treatment Systems(MITS)". Joint Program Executive Office for Chemical and Biological Defense. United States Army.
^ Chen VP, Gao Y, Geng L, Parks RJ, Pang YP, Brimijoin S (Feb 2015). "Plasma butyrylcholinesterase regulates ghrelin to control aggression". Proceedings of the National Academy of Sciences of the United States of America. 112 (7): 2251–6. doi:10.1073/pnas.1421536112. PMID 25646463.
^ Brus B, Košak U, Turk S, Pišlar A, Coquelle N, Kos J, Stojan J, Colletier JP, Gobec S (Oct 2014). "Discovery, biological evaluation, and crystal structure of a novel nanomolar selective butyrylcholinesterase inhibitor". Journal of Medicinal Chemistry. 57 (19): 8167–79. doi:10.1021/jm501195e. PMID 25226236.

External links

Butyrylcholinesterase at the US National Library of Medicine Medical Subject Headings (MeSH)
Human BCHE genome location and BCHE gene details page in the UCSC Genome Browser.

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 成人におけるコカイン使用障害：病態、薬理学、臨床症状、医学的転帰、および診断 cocaine use disorder in adults epidemiology pharmacology clinical manifestations medical consequences and diagnosis

English Journal

Beverages of lemon juice and exotic noni and papaya with potential for anticholinergic effects.

Gironés-Vilaplana A1, Valentão P2, Andrade PB2, Ferreres F1, Moreno DA3, García-Viguera C1.
Food chemistry.Food Chem.2015 Mar 1;170:16-21. doi: 10.1016/j.foodchem.2014.08.021. Epub 2014 Aug 17.
Lemon (Citrus limon (L.) Burm. f.) juice beverages enriched either with noni (Morinda citrifolia L.) (LN) or papaya (Carica papaya L.) (LP), were characterized by HPLC-DAD-ESI/MS(n), the antioxidant capacity was evaluated by (DPPH), superoxide (O2(-)), hydroxyl radicals (OH) and hypochlorous acid (H
PMID 25306312

Resistance in cholinesterase activity after an acute and subchronic exposure to azinphos-methyl in the freshwater gastropod Biomphalaria straminea.

Bianco K1, Otero S1, Balazote Oliver A1, Nahabedian D2, Kristoff G3.
Ecotoxicology and environmental safety.Ecotoxicol Environ Saf.2014 Nov;109:85-92. doi: 10.1016/j.ecoenv.2014.07.038. Epub 2014 Aug 28.
Organophosphorous and carbamates insecticides are ones of the most popular classes of pesticides used in agriculture. Its success relies on their high acute toxicity and rapid environmental degradation. These insecticides inhibit cholinesterase and cause severe effects on aquatic non-target species,
PMID 25173743

Protective effect of quercetin in ecto-enzymes, cholinesterases, and myeloperoxidase activities in the lymphocytes of rats exposed to cadmium.

Abdalla FH1, Cardoso AM, Schmatz R, Gonçalves JF, Baldissarelli J, Martins CC, Zanini D, de Oliveira LS, da Costa P, Pimentel VC, Pereira LB, Lhamas CL, Schetinger MR, Morsch VM, Mazzanti CM.
Molecular and cellular biochemistry.Mol Cell Biochem.2014 Nov;396(1-2):201-11. doi: 10.1007/s11010-014-2155-7. Epub 2014 Jul 27.
The ex vivo and in vitro effects of quercetin on NTPDase, adenosine deaminase (ADA), and acetycholinesterase (AChE) activities in lymphocytes, as well as the effects of quercetin on butyrylcholinesterase (BChE) activity in serum and myeloperoxidase (MPO) activity in plasma were determined in rats. F
PMID 25064450

Japanese Journal

Paraoxonase 1 Correlates with Butyrylcholinesterase and Gamma Glutamyl Transferase in Workers Chronically Exposed to Pesticides

ARAOUD Manel,NEFFETI Fadoua,DOUKI Wahiba,NAJJAR Mohamed Fadhel,KENANI Abderraouf
Journal of occupational health 52(6), 383-388, 2010-11-01
NAID 10026964722

Potential use of cholinesterase activity from tropical green mussel, Perna viridis as a biomarker in effect-based marine monitoring in Indonesia (Special section for JSPS multilateral core university program on "coastal marine science": proceedings on 4th JSPS-VAST joint seminar on 'coastal marine science', Hai Phong, Viet Nam, 26-28 October 2009) -- (Special section: Ocean pollution)

Yaqin Khusnul
Coastal marine science 34(1), 156-164, 2010
NAID 40017386886

Related Pictures

★リンクテーブル★

リンク元	「偽コリンエステラーゼ」「ブチリルコリンエステラーゼ」

「偽コリンエステラーゼ」

BCHE
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1P0P, 4AXB, 4B0P, 2XQG, 1XLV, 2WIK, 2WIL, 1P0Q, 1XLU, 4BDS, 2XQF, 2PM8, 2XQK, 4AQD, 4BBZ, 2WID, 2XMB, 1XLW, 2XMC, 4TPK, 2XMG, 2XMD, 3DKK, 3O9M, 2WSL, 2WIJ, 1P0I, 2WIG, 2XQJ, 3DJY, 1P0M, 4B0O, 2XQI, 2Y1K, 4XII, 2WIF, 2J4C
Identifiers
Aliases	BCHE, CHE1, CHE2, E1, butyrylcholinesterase
External IDs	OMIM: 177400 MGI: 894278 HomoloGene: 20065 GeneCards: BCHE
Genetically Related Diseases
	cardiovascular system disease
Targeted by Drug
	bambuterol, physostigmine, pyridostigmine, rivastigmine, tacrine
Gene ontology
Molecular function	• carboxylic ester hydrolase activity; • beta-amyloid binding; • cholinesterase activity; • choline binding; • catalytic activity; • identical protein binding; • acetylcholinesterase activity; • enzyme binding; • hydrolase activity; • hydrolase activity, acting on ester bonds;
Cellular component	• endoplasmic reticulum lumen; • blood microparticle; • membrane; • extracellular region; • endoplasmic reticulum; • nuclear envelope lumen; • extracellular space;
Biological process	• choline metabolic process; • response to nutrient; • neuroblast differentiation; • response to glucocorticoid; • negative regulation of synaptic transmission; • learning; • cocaine metabolic process; • response to alkaloid; • response to folic acid; • response to drug; • negative regulation of cell proliferation;
	Sources:Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	590
	12038
	ENSG00000114200
	ENSMUSG00000027792
	P06276
	Q03311
	NM_000055
	NM_009738
	NP_000046
	NP_033868.3; NP_033868
	Wikidata
View/Edit Human	View/Edit Mouse

　　[★]

英: pseudocholinesterase
同: 偽ChE、アシルコリン・アシルヒドロラーゼ acetylcholine acylhydrolase、偽性コリンエステラーゼ
関: butyrylcholinesterase

[show details]

偽コリンエステラーゼ : 約 806 件
偽性コリンエステラーゼ : 約 1,210 件

英: ChE pseudocholinesterase

see コリンエステラーゼ(ChE)

臨床関連

偽コリンエステラーゼの血中濃度は肝障害時に減少するので、肝機能の検査項目に加えられている (SPC.156)

低値：肝硬変、肝炎、有機リン系農薬中毒

「ブチリルコリンエステラーゼ」

　　[★]

英: butyrylcholinesterase
同: BuChE
関: 偽コリンエステラーゼ pseudocholinesterase

[WikiPathways-13] The interactive pathway map can be edited at WikiPathways: "IrinotecanPathway_WP46359".

[1] "Diseases that are genetically associated with BCHE view/edit references on wikidata".

[2] "Drugs that physically interact with Butyrylcholinesterase view/edit references on wikidata".

[3] "Human PubMed Reference:".

[4] "Mouse PubMed Reference:".

[umm_serum-5] Jasmin L (2013-05-28). "Cholinesterase - blood". University of Maryland Medical Center.

[pmid1769657-6] Allderdice PW, Gardner HA, Galutira D, Lockridge O, LaDu BN, McAlpine PJ (Oct 1991). "The cloned butyrylcholinesterase (BCHE) gene maps to a single chromosome site, 3q26". Genomics. 11 (2): 452–4. doi:10.1016/0888-7543(91)90154-7. PMID 1769657.

[pmid6992635-7] Whittaker M (1980). "Plasma cholinesterase variants and the anaesthetist". Anaesthesia. 35 (2): 174–197. doi:10.1111/j.1365-2044.1980.tb03800.x. PMID 6992635.

[urlPseudocholinesterase_Deficiency-8] "Pseudocholinesterase Deficiency". Medscape. WebMD LLC.

[pmid18710224-9] Zheng F, Yang W, Ko MC, Liu J, Cho H, Gao D, Tong M, Tai HH, Woods JH, Zhan CG (Sep 2008). "Most efficient cocaine hydrolase designed by virtual screening of transition states". Journal of the American Chemical Society. 130 (36): 12148–55. doi:10.1021/ja803646t. PMC 2646118. PMID 18710224. Lay summary – ScienceDaily.

[10] "Entrez Gene: BCHE butyrylcholinesterase".

[urlMedical_Identification_and_Treatment_Systems.28MITS.29-11] "Medical Identification and Treatment Systems(MITS)". Joint Program Executive Office for Chemical and Biological Defense. United States Army.

[12] Chen VP, Gao Y, Geng L, Parks RJ, Pang YP, Brimijoin S (Feb 2015). "Plasma butyrylcholinesterase regulates ghrelin to control aggression". Proceedings of the National Academy of Sciences of the United States of America. 112 (7): 2251–6. doi:10.1073/pnas.1421536112. PMID 25646463.

[pmid25226236-14] Brus B, Košak U, Turk S, Pišlar A, Coquelle N, Kos J, Stojan J, Colletier JP, Gobec S (Oct 2014). "Discovery, biological evaluation, and crystal structure of a novel nanomolar selective butyrylcholinesterase inhibitor". Journal of Medicinal Chemistry. 57 (19): 8167–79. doi:10.1021/jm501195e. PMID 25226236.

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案内

案内

butyrylcholinesterase