Butyrylcholinesterase

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, BCHED
External IDs	OMIM: 177400 MGI: 894278 HomoloGene: 20065 GeneCards: BCHE
Gene location (Human) Chr. Chromosome 3 (human)[1] Band 3q26.1 Start 165,772,904 bp[1] End 165,837,462 bp[1]
Gene location (Mouse) Chr. Chromosome 3 (mouse)[2] Band 3|3 E3 Start 73,635,808 bp[2] End 73,708,415 bp[2]
RNA expression pattern Bgee Top expressed in parietal pleura liver Right lobe of liver visceral pleura More reference expression data BioGPS More reference expression data
Gene ontology Molecular function GO:0004091 carboxylic ester hydrolase activity amyloid-beta 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 negative regulation of cell population proliferation Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	590	12038
Ensembl	ENSG00000114200	ENSMUSG00000027792
UniProt	P06276	Q03311
RefSeq (mRNA)	NM_000055	NM_009738
RefSeq (protein)	NP_000046	NP_033868
Location (UCSC)	Chr 3: 165.77 – 165.84 Mb	Chr 3: 73.64 – 73.71 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Butyrylcholinesterase (HGNC symbol BCHE; EC 3.1.1.8), 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.

Potential physiological role[]

Butyrylcholinesterase may be a physiological ghrelin regulator.^[8]

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.^[9]

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 agents[]

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]

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.^[12]

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.^[13]

Interactive pathway map[]

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

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|alt=Irinotecan Pathway edit]]

Irinotecan Pathway edit

1. ^ 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.^[14]
• Hybrid/bitopic ligands^[15]

Nomenclature[]

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

See also[]

• Cholinesterases
• Dibucaine number

References[]

Further reading[]

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.