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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/09/18 18:37:13」(JST)

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This article is about a human gene. For Bachelor of Chemical Engineering (BChE) degree, see Bachelor of Engineering.

Butyrylcholinesterase (also known as pseudocholinesterase, plasma cholinesterase,^[1] BCHE, or BuChE) is a non-specific cholinesterase enzyme that hydrolyses many different choline esters. In humans, it is found primarily in the liver^[1] and is encoded by the BCHE gene.^[2]

It is very similar to the neuronal acetylcholinesterase, which is also known as RBC or erythrocyte cholinesterase.^[1] The term "serum cholinesterase" is generally used in reference to a clinical test that reflects levels of both of these enzymes in the blood.^[1]

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

Clinical significance

Pseudocholinesterase deficiency results in delayed metabolism of only a few compounds of clinical significance, including the following: succinylcholine, mivacurium, procaine, 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.^[3]

In 2008, an experimental new drug was discovered for the potential treatment of cocaine abuse and overdose based on the pseudocholiesterase 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.^[4] 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.^[5]

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.

Interactive pathway map

Click on genes, proteins and metabolites below to link to respective articles. ^[6]

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Irinotecan Pathway edit

References

^ ^a ^b ^c ^d http://www.umm.edu/ency/article/003358.htm
^ Allderdice PW, Gardner HA, Galutira D, Lockridge O, LaDu BN, McAlpine PJ (October 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.
^ emedicine.medscape.com, Pseudocholinesterase deficiency;
^ Zheng F, Yang W, Ko MC, Liu J, Cho H, Gao D, Tong M, Tai HH, Woods JH, Zhan CG (September 2008). "Most efficient cocaine hydrolase designed by virtual screening of transition states". J. Am. Chem. Soc. 130 (36): 12148–55. doi:10.1021/ja803646t. PMC 2646118. PMID 18710224. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2646118/. Lay summary – ScienceDaily.
^ "Entrez Gene: BCHE butyrylcholinesterase". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=590.
^ The interactive pathway map can be edited at WikiPathways: "IrinotecanPathway_WP46359". http://www.wikipathways.org/index.php/Pathway:WP46359.

External links

Butyrylcholinesterase at the US National Library of Medicine Medical Subject Headings (MeSH)

English Journal

Protection against paraoxon toxicity by an intravenous pretreatment with polyethylene-glycol-conjugated recombinant butyrylcholinesterase in macaques.

Rosenberg YJ1, Gearhart J2, Mao L3, Jiang X3, Hernandez-Abanto S3.Author information 1PlantVax Inc, Rockville, MD 20850, United States. Electronic address: yjr@plantvax.com.2Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD 20817, United States.3PlantVax Inc, Rockville, MD 20850, United States.AbstractRecombinant (r) butyrylcholinesterase (rBChE) produced in CHO cells is being developed as a prophylactic countermeasure against neurotoxicity resulting from exposure to organophosphates (OPs) in the form of pesticides and nerve agents. To evaluate the efficacy of a parenteral pretreatment, a PEGylated macaque (Ma) form of rBChE was administered into homologous animals to ensure good plasma retention without immunogenicity. Thus, macaques were administered PEG-rMaBChE at either 5 or 7mg/kg intravenously (i.v.) and exposed subcutaneously to 12μg/kg of the potent pesticide paraoxon (Px) at 1h or at 1 and 72h, respectively. Protection was measured by the ability of rBChE prophylaxis to prevent the inhibition of circulating acetylcholinesterase on red blood cells (RBC-AChE). In rBChE-pretreated animals, no inhibition of RBC-AChE activity after the first Px exposure and only a 10-20% reduction after the second exposure were observed as compared to a 75% RBC-AChE inhibition usually obtained without pretreatment. In addition, these studies raised other interesting issues. The lipophilic nature of Px, appears to result in early and transient inhibition of RBC-AChE as a result of transfer of OP bound to RBC even in BChE-pretreated animals. The protection by a single injection of rBChE against two administrations of Px represents the first example of protection by an i.v. rBChE pretreatment against a pesticide such as Px and bodes well for a parenteral rHuBChE pretreatment as an OP countermeasure in humans.
Chemico-biological interactions.Chem Biol Interact.2014 Mar 5;210:20-5. doi: 10.1016/j.cbi.2013.12.010. Epub 2013 Dec 30.
Recombinant (r) butyrylcholinesterase (rBChE) produced in CHO cells is being developed as a prophylactic countermeasure against neurotoxicity resulting from exposure to organophosphates (OPs) in the form of pesticides and nerve agents. To evaluate the efficacy of a parenteral pretreatment, a PEGylat
PMID 24384224

Serum butyrylcholinesterase and the risk of future type 2 diabetes: the Kansai Healthcare Study.

Sato KK1, Hayashi T, Maeda I, Koh H, Harita N, Uehara S, Onishi Y, Oue K, Nakamura Y, Endo G, Kambe H, Fukuda K.Author information 1Department of Preventive Medicine and Environmental Health, Osaka City University Graduate School of Medicine, Osaka, Japan.AbstractOBJECTIVE: Butyrylcholinesterase is synthesized in the liver. The serum butyrylcholinesterase level has been cross-sectionally reported to be higher in patients with diabetes, hyperlipidaemia, obesity and fatty liver than in those without them. It is not known whether serum butyrylcholinesterase is associated with the risk of future type 2 diabetes.
Clinical endocrinology.Clin Endocrinol (Oxf).2014 Mar;80(3):362-7. doi: 10.1111/cen.12171. Epub 2013 May 20.
OBJECTIVE: Butyrylcholinesterase is synthesized in the liver. The serum butyrylcholinesterase level has been cross-sectionally reported to be higher in patients with diabetes, hyperlipidaemia, obesity and fatty liver than in those without them. It is not known whether serum butyrylcholinesterase is
PMID 23418907

Molecular modeling evidence for his438 flip in the mechanism of butyrylcholinesterase hysteretic behavior.

Lushchekina SV1, Nemukhin AV, Varfolomeev SD, Masson P.Author information 1Computer Modeling of Biomolecular Systems Lab, N.M. Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, 4 Kosygina St., 119334, Moscow, Russia, sofya.lushchekina@gmail.com.AbstractCholinesterases display a hysteretic behavior with certain substrates and irreversible inhibitors. For years, this behavior has remained puzzling. However, several lines of evidence indicated that it is caused by perturbation of the catalytic triad and its water environment. In the present study, using molecular dynamics simulations of Ala328Cys BuChE mutant and wild-type BuChE in the absence and presence of a co-solvent (sucrose, glycerol), we provide evidence that hysteresis originates in a flip of the catalytic triad histidine (His438). This event is controlled by water molecules that interact with active site residues. The physiological significance of this phenomenon is still an issue.
Journal of molecular neuroscience : MN.J Mol Neurosci.2014 Mar;52(3):434-45. doi: 10.1007/s12031-013-0178-2. Epub 2013 Dec 6.
Cholinesterases display a hysteretic behavior with certain substrates and irreversible inhibitors. For years, this behavior has remained puzzling. However, several lines of evidence indicated that it is caused by perturbation of the catalytic triad and its water environment. In the present study, us
PMID 24310732

Japanese Journal

血清コリンエステラーゼ(ChE)の異常と病態 (今月の特集日常検査から見える病態 : 生化学検査(2))

矢内充
臨床検査 57(12), 1495-1499, 2013-11
NAID 40019835426

偽性コリンエステラーゼ欠損症患者に対する硬膜外麻酔併用全静脈麻酔の経験

渡部達範,生駒美穂,渋江智栄子,馬場洋
日本臨床麻酔学会誌 = The Journal of Japan Society for Clinical Anesthesia 32(4), 569-572, 2012-07-14
NAID 10030832406

Erratum:偽性コリンエステラーゼ欠損症患者に対する硬膜外麻酔併用全静脈麻酔の経験[日本臨床麻酔学会誌Vol. 32 (2012) No. 4 p. 569-572]

渡部達範,生駒美穂,渋江智栄子,馬場洋
日本臨床麻酔学会誌 32(7), 994-994, 2012
Vol. 32 (2012) No. 4掲載の短報「偽性コリンエステラーゼ欠損症患者に対する硬膜外麻酔併用全静脈麻酔の経験」の記述を訂正いたします．
NAID 130004450124

Related Pictures

Cholinergic drugs thea AN UNUSUAL CAUSE OF DELAYED RECOVERY FROM NEUROMUSCULAR PARALYSIS DUR… S. Cholinesterase estimation Cholinesterase serum | Labpedia.net

★リンクテーブル★

リンク元	「コリンエステラーゼ」「偽コリンエステラーゼ」「ブチリルコリンエステラーゼ」
拡張検索	「pseudocholinesterase deficiency」

「コリンエステラーゼ」

Butyrylcholinesterase
	; PDB rendering based on 1p0i.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	1P0I, 1P0M, 1P0P, 1P0Q, 1XLU, 1XLV, 1XLW, 2J4C, 2PM8, 2WID, 2WIF, 2WIG, 2WIJ, 2WIK, 2WIL, 2WSL, 2XMB, 2XMC, 2XMD, 2XMG, 2XQF, 2XQG, 2XQI, 2XQJ, 2XQK, 2Y1K, 3DJY, 3DKK, 3O9M, 4AQD, 4AXB, 4B0O, 4B0P
Identifiers
Symbols	BCHE; CHE1; E1
External IDs	OMIM: 177400 MGI: 894278 HomoloGene: 20065 ChEMBL: 1914 GeneCards: BCHE Gene
EC number	3.1.1.8
Gene Ontology
Molecular function	• beta-amyloid binding; • catalytic activity; • acetylcholinesterase activity; • acetylcholinesterase activity; • carboxylesterase activity; • cholinesterase activity; • cholinesterase activity; • enzyme binding; • choline binding;
Cellular component	• extracellular region; • extracellular region; • extracellular space; • membrane fraction; • nuclear envelope lumen; • endoplasmic reticulum lumen; • membrane;
Biological process	• synaptic transmission, cholinergic; • learning; • metabolic process; • choline metabolic process; • response to drug; • response to alkaloid; • cocaine metabolic process; • negative regulation of synaptic transmission; • response to glucocorticoid stimulus; • response to folic acid;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	This box: view; talk; edit;

　　[★]

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

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