Butyrylcholinesterase

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This article is about a human gene. For Bachelor of Chemical Engineering (BChE) degree, see Bachelor of Engineering.
Butyrylcholinesterase
Protein BCHE PDB 1p0i.png
PDB rendering based on 1p0i.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols BCHE ; CHE1; CHE2; E1
External IDs OMIM177400 MGI894278 HomoloGene20065 ChEMBL: 1914 GeneCards: BCHE Gene
EC number 3.1.1.8
RNA expression pattern
PBB GE BCHE 205433 at tn.png
More reference expression data
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:
165.49 – 165.56 Mb
Chr 3:
73.64 – 73.71 Mb
PubMed search [1] [2]

Butyrylcholinesterase (BCHE, or BuChE), also known as pseudocholinesterase or plasma cholinesterase[1]) 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] Assay of butyrylcholinesterase activity in plasma can be used as a liver function test as both hypercholinesterasemia and hypocholinesterasemia indicate pathological processes.[3]

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[edit]

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.[4]

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.[5] 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.[6]

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[edit]

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.[7]

Interactive pathway map[edit]

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

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IrinotecanPathway_WP46359 go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article Go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article Go to article go to article
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Irinotecan Pathway edit
  1. ^ The interactive pathway map can be edited at WikiPathways: "IrinotecanPathway_WP46359". 

See also[edit]

Cholinesterases

References[edit]

  1. ^ a b c d Jasmin L (2013/05/28). "Cholinesterase - blood". University of Maryland Medical Center. 
  2. ^ 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. 
  3. ^ Pohanka M (2013). "Butyrylcholinesterase as a biochemical marker". Bratislavske Lekarske Listy 114 (12): 726–734. doi:10.4149/BLL_2013_153. PMID 24329513. 
  4. ^ "Pseudocholinesterase Deficiency". Medscape. WebMD LLC. 
  5. ^ 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. Lay summaryScienceDaily. 
  6. ^ "Entrez Gene: BCHE butyrylcholinesterase". 
  7. ^ "Medical Identification and Treatment Systems(MITS)". Joint Program Executive Office for Chemical and Biological Defense. United States Army. 

Further reading[edit]

External links[edit]