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Butyrylcholinesterase, also known as pseudocholinesterase, BCHE or BuChE, is an enzyme that, in humans, is encoded by the BCHE gene.[1] Butyrylcholinesterase is also called serum cholinesterase. It is very similar to the neuronal acetylcholinesterase, and is a non-specific cholinesterase found in the blood plasma, which hydrolyses many different choline esters. 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.[2]

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.[3] 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.[4]

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.

See also

Cholinesterase enzyme


  1. 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.
  2., Pseudocholinesterase deficiency;
  3. 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.
  4. Entrez Gene: BCHE butyrylcholinesterase.

Further reading

  • Lockridge O (1989). Structure of human serum cholinesterase.. Bioessays 9 (4): 125–8.
  • Allderdice PW, Gardner HA, Galutira D, et al. (1992). The cloned butyrylcholinesterase (BCHE) gene maps to a single chromosome site, 3q26.. Genomics 11 (2): 452–4.
  • Gaughan G, Park H, Priddle J, et al. (1992). Refinement of the localization of human butyrylcholinesterase to chromosome 3q26.1-q26.2 using a PCR-derived probe.. Genomics 11 (2): 455–8.
  • Arpagaus M, Kott M, Vatsis KP, et al. (1990). Structure of the gene for human butyrylcholinesterase. Evidence for a single copy.. Biochemistry 29 (1): 124–31.
  • Nogueira CP, McGuire MC, Graeser C, et al. (1990). Identification of a frameshift mutation responsible for the silent phenotype of human serum cholinesterase, Gly 117 (GGT----GGAG).. Am. J. Hum. Genet. 46 (5): 934–42.
  • McGuire MC, Nogueira CP, Bartels CF, et al. (1989). Identification of the structural mutation responsible for the dibucaine-resistant (atypical) variant form of human serum cholinesterase.. Proc. Natl. Acad. Sci. U.S.A. 86 (3): 953–7.
  • Prody CA, Zevin-Sonkin D, Gnatt A, et al. (1987). Isolation and characterization of full-length cDNA clones coding for cholinesterase from fetal human tissues.. Proc. Natl. Acad. Sci. U.S.A. 84 (11): 3555–9.
  • Lockridge O, Adkins S, La Du BN (1987). Location of disulfide bonds within the sequence of human serum cholinesterase.. J. Biol. Chem. 262 (27): 12945–52.
  • McTiernan C, Adkins S, Chatonnet A, et al. (1987). Brain cDNA clone for human cholinesterase.. Proc. Natl. Acad. Sci. U.S.A. 84 (19): 6682–6.
  • Lockridge O, Bartels CF, Vaughan TA, et al. (1987). Complete amino acid sequence of human serum cholinesterase.. J. Biol. Chem. 262 (2): 549–57.
  • Jbilo O, Toutant JP, Vatsis KP, et al. (1994). Promoter and transcription start site of human and rabbit butyrylcholinesterase genes.. J. Biol. Chem. 269 (33): 20829–37.
  • Mattes C, Bradley R, Slaughter E, Browne S (1996). Cocaine and butyrylcholinesterase (BChE): determination of enzymatic parameters.. Life Sci. 58 (13): PL257–61.
  • Iida S, Kinoshita M, Fujii H, et al. (1996). Mutations of human butyrylcholinesterase gene in a family with hypocholinesterasemia.. Hum. Mutat. 6 (4): 349–51.
  • Kamendulis LM, Brzezinski MR, Pindel EV, et al. (1996). Metabolism of cocaine and heroin is catalyzed by the same human liver carboxylesterases.. J. Pharmacol. Exp. Ther. 279 (2): 713–7.
  • Hidaka K, Iuchi I, Tomita M, et al. (1998). Genetic analysis of a Japanese patient with butyrylcholinesterase deficiency.. Ann. Hum. Genet. 61 (Pt 6): 491–6.
  • Browne SP, Slaughter EA, Couch RA, et al. (1998). The influence of plasma butyrylcholinesterase concentration on the in vitro hydrolysis of cocaine in human plasma.. Biopharmaceutics & drug disposition 19 (5): 309–14.
  • Altamirano CV, Lockridge O (1999). Conserved aromatic residues of the C-terminus of human butyrylcholinesterase mediate the association of tetramers.. Biochemistry 38 (40): 13414–22.
  • Darvesh S, Kumar R, Roberts S, et al. (2002). Butyrylcholinesterase-Mediated enhancement of the enzymatic activity of trypsin.. Cell. Mol. Neurobiol. 21 (3): 285–96.
  • Barta C, Sasvari-Szekely M, Devai A, et al. (2002). Analysis of mutations in the plasma cholinesterase gene of patients with a history of prolonged neuromuscular block during anesthesia.. Mol. Genet. Metab. 74 (4): 484–8.

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