View source for Butyrylcholinesterase

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{{Short description|Mammalian protein found in humans}}
{{Infobox_gene}}

'''Butyrylcholinesterase''' ([[HUGO Gene Nomenclature Committee|HGNC]] symbol '''BCHE'''; EC 3.1.1.8), [[#Nomenclature|also known as]] '''BChE''', '''BuChE''', '''BuChase''', '''pseudocholinesterase''', or '''plasma (cholin)esterase''',<ref name=umm_serum>{{cite web | url = http://www.umm.edu/ency/article/003358.htm | title = Cholinesterase - blood | author = Jasmin L | publisher = University of Maryland Medical Center | date = 2013-05-28 | access-date = 2011-09-07 | archive-date = 2012-10-30 | archive-url = https://web.archive.org/web/20121030134808/http://www.umm.edu/ency/article/003358.htm | url-status = dead }}</ref> is a nonspecific [[cholinesterase]] enzyme that hydrolyses many different [[choline]]-based [[ester]]s. In humans, it is made in the liver, found mainly in [[blood plasma]], and encoded by the ''BCHE'' [[gene]].<ref name="pmid1769657">{{cite journal | vauthors = Allderdice PW, Gardner HA, Galutira D, Lockridge O, LaDu BN, McAlpine PJ | title = The cloned butyrylcholinesterase (BCHE) gene maps to a single chromosome site, 3q26 | journal = Genomics | volume = 11 | issue = 2 | pages = 452–454 | date = October 1991 | pmid = 1769657 | doi = 10.1016/0888-7543(91)90154-7 | hdl-access = free | hdl = 2027.42/29109 }}</ref>

It is very similar to the neuronal [[acetylcholinesterase]], which is also known as RBC or erythrocyte cholinesterase.<ref name=umm_serum /> The term "serum cholinesterase" is generally used in reference to a clinical test that reflects levels of both of these enzymes in the blood.<ref name=umm_serum /> 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.<ref name="pmid6992635">{{cite journal | vauthors = Whittaker M | title = Plasma cholinesterase variants and the anaesthetist | journal = Anaesthesia | volume = 35 | issue = 2 | pages = 174–197 | date = February 1980 | pmid = 6992635 | doi = 10.1111/j.1365-2044.1980.tb03800.x | s2cid = 32806785 | doi-access = free }}</ref>

[[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.

== Potential physiological role ==

Butyrylcholinesterase may be a physiological [[ghrelin]] regulator.<ref>{{cite journal | vauthors = Chen VP, Gao Y, Geng L, Parks RJ, Pang YP, Brimijoin S | title = Plasma butyrylcholinesterase regulates ghrelin to control aggression | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 112 | issue = 7 | pages = 2251–2256 | date = February 2015 | pmid = 25646463 | pmc = 4343161 | doi = 10.1073/pnas.1421536112 | doi-access = free | bibcode = 2015PNAS..112.2251C }}</ref>

==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.{{cn|date=May 2024}}

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 one minute. In normal subjects, skeletal muscle function returns to normal approximately five 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 eight 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.<ref name="urlPseudocholinesterase Deficiency">{{cite journal | url = http://emedicine.medscape.com/article/247019-overview+emedicine.medscape.com | title = Pseudocholinesterase Deficiency | publisher = WebMD LLC | journal = Medscape | date = 15 July 2021 }}</ref>

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.<ref>{{cite web |title = Entrez Gene: BCHE butyrylcholinesterase| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=590}}</ref>

Finally, pseudocholinesterase metabolism of [[procaine]] results in formation of [[paraaminobenzoic acid]] (PABA). If the patient receiving procaine is on [[sulfonamide (medicine)|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]].{{cn|date=May 2024}}

=== Prophylactic countermeasure against nerve agents ===

Butyrylcholinesterase is a [[prophylactic]] [[countermeasure]] against [[organophosphate]] [[nerve agent]]s. 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 [[stoichiometry|stoichiometric]] protection against the entire spectrum of organophosphate nerve agents.<ref name="urlMedical Identification and Treatment Systems(MITS)">{{cite web | url = http://www.jpeocbd.osd.mil/packs/Default.aspx?pg=1207 | title = Medical Identification and Treatment Systems(MITS) | work = Joint Program Executive Office for Chemical and Biological Defense | publisher = United States Army | access-date = 2014-08-13 | archive-url = https://web.archive.org/web/20161028024829/http://www.jpeocbd.osd.mil/packs/Default.aspx?pg=1207 | archive-date = 2016-10-28 }}</ref>

=== Prophylactic against cocaine addiction ===

An experimental new drug was developed for the potential treatment of [[cocaine]] abuse and overdose based on the pseudocholinesterase structure (it was a human BChE mutant with improved catalytic efficiency). 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.<ref name="pmid18710224">{{cite journal | vauthors = Zheng F, Yang W, Ko MC, Liu J, Cho H, Gao D, Tong M, Tai HH, Woods JH, Zhan CG | display-authors = 6 | title = Most efficient cocaine hydrolase designed by virtual screening of transition states | journal = Journal of the American Chemical Society | volume = 130 | issue = 36 | pages = 12148–12155 | date = September 2008 | pmid = 18710224 | pmc = 2646118 | doi = 10.1021/ja803646t | bibcode = 2008JAChS.13012148Z }}
* {{cite press release |date=September 16, 2008 |title=Potential New Drug For Cocaine Addiction And Overdose |website=ScienceDaily |url=https://www.sciencedaily.com/releases/2008/09/080915164427.htm}}</ref>

Transplantation of skin cells modified to express the enhanced form of butyrylcholinesterase into mice enables the long-term release of the enzyme and efficiently protects the mice from cocaine-seeking behavior and cocaine overdose.<ref>{{cite journal | vauthors = Li Y, Kong Q, Yue J, Gou X, Xu M, Wu X | title = Genome-edited skin epidermal stem cells protect mice from cocaine-seeking behaviour and cocaine overdose | journal = Nature Biomedical Engineering | volume = 3 | issue = 2 | pages = 105–113 | date = February 2019 | pmid = 30899600 | pmc = 6423967 | doi = 10.1038/s41551-018-0293-z }}</ref>

=== Marker for risk of SIDS ===

Research published by the SIDS and Sleep Apnoea Research Group of The Children's Hospital in Westmead, New South Wales, Australia, in the May 6, 2022 edition of in ''[[The Lancet]]'' indicates that BChE may be a marker for babies that are at risk of [[sudden infant death syndrome]] (SIDS). That is, lower levels of BChE were associated with an increased risk of SIDS.<ref>{{cite journal | vauthors = Harrington CT, Hafid NA, Waters KA | title = Butyrylcholinesterase is a potential biomarker for Sudden Infant Death Syndrome | journal = eBioMedicine | volume = 80 | pages = 104041 | date = June 2022 | pmid = 35533499 | pmc = 9092508 | doi = 10.1016/j.ebiom.2022.104041 | publisher = The Children's Hospital in Westmead, New South Wales, Australia | s2cid = 248645079 }}</ref>

== Interactive pathway map ==
{{IrinotecanPathway_WP229|highlight=Butyrylcholinesterase}}

== Inhibitors ==
{{See also|Cholinesterase inhibitor}}
* [[Cannabinoid|Phytocannabinoids]]<ref>{{cite journal | vauthors = Puopolo T, Liu C, Ma H, Seeram NP | title = Inhibitory Effects of Cannabinoids on Acetylcholinesterase and Butyrylcholinesterase Enzyme Activities | journal = Medical Cannabis and Cannabinoids | volume = 5 | issue = 1 | pages = 85–94 | date = 2022-04-19 | pmid = 35702400 | doi = 10.1159/000524086 | pmc = 9149358 | doi-access = free }}</ref>
** [[Cannabidiol]]
** Δ8-[[tetrahydrocannabinol]]
** [[Cannabigerol]]
** [[Cannabigerolic acid|Cannabigerolic]] acid
** [[Cannabicitran]]
** [[Cannabidivarin]]
** [[Cannabichromene]]
** [[Cannabinol]]
* [[Cymserine]] and derivatives
* [[Profenamine]]
* [[Rivastigmine]]
* [[Tacrine]]
* (+)-ZINC-12613047: IC<sub>50</sub> human BChE 13nM, high selectivity over [[AChE]].<ref name="pmid25226236">{{cite journal | vauthors = Brus B, Košak U, Turk S, Pišlar A, Coquelle N, Kos J, Stojan J, Colletier JP, Gobec S | display-authors = 6 | title = Discovery, biological evaluation, and crystal structure of a novel nanomolar selective butyrylcholinesterase inhibitor | journal = Journal of Medicinal Chemistry | volume = 57 | issue = 19 | pages = 8167–8179 | date = October 2014 | pmid = 25226236 | doi = 10.1021/jm501195e }}</ref>
* Hybrid/bitopic ligands<ref>{{cite journal | vauthors = Messerer R, Dallanoce C, Matera C, Wehle S, Flammini L, Chirinda B, Bock A, Irmen M, Tränkle C, Barocelli E, Decker M, Sotriffer C, De Amici M, Holzgrabe U | display-authors = 6 | title = Novel bipharmacophoric inhibitors of the cholinesterases with affinity to the muscarinic receptors M<sub>1</sub> and M<sub>2</sub> | journal = MedChemComm | volume = 8 | issue = 6 | pages = 1346–1359 | date = June 2017 | pmid = 30108847 | pmc = 6072511 | doi = 10.1039/c7md00149e }}</ref>

==Nomenclature==
The nomenclatural variations of BCHE and of cholinesterases generally are discussed at ''[[Cholinesterase#Types and nomenclature|Cholinesterase § Types and nomenclature]]''.

== See also ==
* [[Cholinesterase]]s
* [[Dibucaine number]]

== References ==
{{reflist|32em}}

== Further reading ==
{{refbegin|32em}}
* {{cite journal | vauthors = Bodur E, Cokugras AN | title = The effects of indole-3-acetic acid on human and horse serum butyrylcholinesterase | journal = Chemico-Biological Interactions | volume = 157-158 | issue = 16 | pages = 375–378 | date = December 2005 | pmid = 16429500 | doi = 10.1016/j.cbi.2005.10.061 }}
* {{cite journal | vauthors = Lockridge O | title = Structure of human serum cholinesterase | journal = BioEssays | volume = 9 | issue = 4 | pages = 125–128 | date = October 1988 | pmid = 3067729 | doi = 10.1002/bies.950090406 | hdl-access = free | s2cid = 29779511 | hdl = 2027.42/50189 }}
* {{cite journal | vauthors = Allderdice PW, Gardner HA, Galutira D, Lockridge O, LaDu BN, McAlpine PJ | title = The cloned butyrylcholinesterase (BCHE) gene maps to a single chromosome site, 3q26 | journal = Genomics | volume = 11 | issue = 2 | pages = 452–454 | date = October 1991 | pmid = 1769657 | doi = 10.1016/0888-7543(91)90154-7 | hdl-access = free | hdl = 2027.42/29109 }}
* {{cite journal | vauthors = Gaughan G, Park H, Priddle J, Craig I, Craig S | title = Refinement of the localization of human butyrylcholinesterase to chromosome 3q26.1-q26.2 using a PCR-derived probe | journal = Genomics | volume = 11 | issue = 2 | pages = 455–458 | date = October 1991 | pmid = 1769658 | doi = 10.1016/0888-7543(91)90155-8 }}
* {{cite journal | vauthors = Arpagaus M, Kott M, Vatsis KP, Bartels CF, La Du BN, Lockridge O | title = Structure of the gene for human butyrylcholinesterase. Evidence for a single copy | journal = Biochemistry | volume = 29 | issue = 1 | pages = 124–131 | date = January 1990 | pmid = 2322535 | doi = 10.1021/bi00453a015 }}
* {{cite journal | vauthors = Nogueira CP, McGuire MC, Graeser C, Bartels CF, Arpagaus M, Van der Spek AF, Lightstone H, Lockridge O, La Du BN | display-authors = 6 | title = Identification of a frameshift mutation responsible for the silent phenotype of human serum cholinesterase, Gly 117 (GGT----GGAG) | journal = American Journal of Human Genetics | volume = 46 | issue = 5 | pages = 934–942 | date = May 1990 | pmid = 2339692 | pmc = 1683584 }}
* {{cite journal | vauthors = McGuire MC, Nogueira CP, Bartels CF, Lightstone H, Hajra A, Van der Spek AF, Lockridge O, La Du BN | display-authors = 6 | title = Identification of the structural mutation responsible for the dibucaine-resistant (atypical) variant form of human serum cholinesterase | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 86 | issue = 3 | pages = 953–957 | date = February 1989 | pmid = 2915989 | pmc = 286597 | doi = 10.1073/pnas.86.3.953 | doi-access = free | bibcode = 1989PNAS...86..953M }}
* {{cite journal | vauthors = Prody CA, Zevin-Sonkin D, Gnatt A, Goldberg O, Soreq H | title = Isolation and characterization of full-length cDNA clones coding for cholinesterase from fetal human tissues | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 84 | issue = 11 | pages = 3555–3559 | date = June 1987 | pmid = 3035536 | pmc = 304913 | doi = 10.1073/pnas.84.11.3555 | doi-access = free | bibcode = 1987PNAS...84.3555P }}
* {{cite journal | vauthors = Lockridge O, Adkins S, La Du BN | title = Location of disulfide bonds within the sequence of human serum cholinesterase | journal = The Journal of Biological Chemistry | volume = 262 | issue = 27 | pages = 12945–12952 | date = September 1987 | pmid = 3115973 | doi = 10.1016/S0021-9258(18)45149-6 | doi-access = free }}
* {{cite journal | vauthors = McTiernan C, Adkins S, Chatonnet A, Vaughan TA, Bartels CF, Kott M, Rosenberry TL, La Du BN, Lockridge O | display-authors = 6 | title = Brain cDNA clone for human cholinesterase | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 84 | issue = 19 | pages = 6682–6686 | date = October 1987 | pmid = 3477799 | pmc = 299147 | doi = 10.1073/pnas.84.19.6682 | doi-access = free | bibcode = 1987PNAS...84.6682M }}
* {{cite journal | vauthors = Lockridge O, Bartels CF, Vaughan TA, Wong CK, Norton SE, Johnson LL | title = Complete amino acid sequence of human serum cholinesterase | journal = The Journal of Biological Chemistry | volume = 262 | issue = 2 | pages = 549–557 | date = January 1987 | pmid = 3542989 | doi = 10.1016/S0021-9258(19)75818-9 | doi-access = free }}
* {{cite journal | vauthors = Jbilo O, Toutant JP, Vatsis KP, Chatonnet A, Lockridge O | title = Promoter and transcription start site of human and rabbit butyrylcholinesterase genes | journal = The Journal of Biological Chemistry | volume = 269 | issue = 33 | pages = 20829–20837 | date = August 1994 | pmid = 8063698 | doi = 10.1016/S0021-9258(17)31897-5 | doi-access = free }}
* {{cite journal | vauthors = Mattes C, Bradley R, Slaughter E, Browne S | title = Cocaine and butyrylcholinesterase (BChE): determination of enzymatic parameters | journal = Life Sciences | volume = 58 | issue = 13 | pages = PL257–PL261 | year = 1996 | pmid = 8622553 | doi = 10.1016/0024-3205(96)00065-3 }}
* {{cite journal | vauthors = Iida S, Kinoshita M, Fujii H, Moriyama Y, Nakamura Y, Yura N, Moriwaki K | title = Mutations of human butyrylcholinesterase gene in a family with hypocholinesterasemia | journal = Human Mutation | volume = 6 | issue = 4 | pages = 349–351 | year = 1996 | pmid = 8680411 | doi = 10.1002/humu.1380060411 | s2cid = 86734543 | doi-access = free }}
* {{cite journal | vauthors = Kamendulis LM, Brzezinski MR, Pindel EV, Bosron WF, Dean RA | title = Metabolism of cocaine and heroin is catalyzed by the same human liver carboxylesterases | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 279 | issue = 2 | pages = 713–717 | date = November 1996 | doi = 10.1016/S0022-3565(25)21180-6 | pmid = 8930175 }}
* {{cite journal | vauthors = Hidaka K, Iuchi I, Tomita M, Watanabe Y, Minatogawa Y, Iwasaki K, Gotoh K, Shimizu C | display-authors = 6 | title = Genetic analysis of a Japanese patient with butyrylcholinesterase deficiency | journal = Annals of Human Genetics | volume = 61 | issue = Pt 6 | pages = 491–496 | date = November 1997 | pmid = 9543549 | doi = 10.1046/j.1469-1809.1997.6160491.x | s2cid = 23291616 }}
* {{cite journal | vauthors = Browne SP, Slaughter EA, Couch RA, Rudnic EM, McLean AM | title = The influence of plasma butyrylcholinesterase concentration on the in vitro hydrolysis of cocaine in human plasma | journal = Biopharmaceutics & Drug Disposition | volume = 19 | issue = 5 | pages = 309–314 | date = July 1998 | pmid = 9673783 | doi = 10.1002/(SICI)1099-081X(199807)19:5<309::AID-BDD108>3.0.CO;2-9 | s2cid = 35577799 }}
* {{cite journal | vauthors = Altamirano CV, Lockridge O | title = Conserved aromatic residues of the C-terminus of human butyrylcholinesterase mediate the association of tetramers | journal = Biochemistry | volume = 38 | issue = 40 | pages = 13414–13422 | date = October 1999 | pmid = 10529218 | doi = 10.1021/bi991475+ }}
* {{cite journal | vauthors = Darvesh S, Kumar R, Roberts S, Walsh R, Martin E | title = Butyrylcholinesterase-Mediated enhancement of the enzymatic activity of trypsin | journal = Cellular and Molecular Neurobiology | volume = 21 | issue = 3 | pages = 285–296 | date = June 2001 | pmid = 11569538 | doi = 10.1023/A:1010947205224 | s2cid = 9861675 | pmc = 11533858 }}
* {{cite journal | vauthors = Barta C, Sasvari-Szekely M, Devai A, Kovacs E, Staub M, Enyedi P | title = Analysis of mutations in the plasma cholinesterase gene of patients with a history of prolonged neuromuscular block during anesthesia | journal = Molecular Genetics and Metabolism | volume = 74 | issue = 4 | pages = 484–488 | date = December 2001 | pmid = 11749053 | doi = 10.1006/mgme.2001.3251 }}
{{refend}}

== External links ==
* {{MeshName|Butyrylcholinesterase}}
* {{UCSC gene info|BCHE}}

{{PDB Gallery|geneid=590}}
{{Esterases}}
{{Neurotransmitter metabolism enzymes}}
{{Acetylcholine metabolism and transport modulators}}

[[Category:Enzymes]]