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Pseudocholinesterase synthesis

Plasma cholinesterase (also known as pseudocholinesterase, butyrylcholinesterase, or BuChE) is a serine hydrolase that catalyses the hydrolysis of esters of choline. It is most known for the metabolism of depolarizing neuromuscular blocking agent succinylcholine (also known as suxamethonium chloride, or SCh) by hydrolysis of the two ester links of choline to succinic acid. BuChE also has aryl acylamidase activity that catalyses the hydrolysis of acyl amides of aromatic amines. BuChE deficiency is usually recognized when an anesthetized patient has prolonged neuromuscular blockade from the administration of SCh. First report of BuChE deficiency by Nilsson in 1953 described a patient who failed to resume spontaneous ventilation after completion of a short operation in the setting of SCh administration; therefore the colloquial name “suxamethonium apnea” was introduced.

BuChE is also responsible for the metabolism of mivacurium, and the concomitant use of mivacurium and SCh in susceptible patients may exaggerate paralytic effect. Since, BuChE enzymes contribute to ester-type local anesthetics hydrolysis to an alkylamine and paraaminobenzoic acid (PABA), patients with abnormal BuChE levels may be at increased risk for toxic side effects. BuChE also accelerates the metabolism of cocaine and has been proposed as a possible pharmacologic agent for the treatment of cocaine toxicity.

There are different molecular forms of BuChE, including monomers and oligomers that are built of identical subunits. The symmetric monomeric form is called the G1 form. The dimeric form, G2, consists of two molecules that are joined by a disulfide bridge between the cysteine residues of each monomer. Two G2 forms held together by hydrophobic interactions can form a tetramer, the G4. These are synthesised in the liver and can be additionally found in kidneys, pancreas, brain and plasma. Interestingly, BuChE enzymes are widely distributed in the nervous system. It has been postulated that BuChE may have important roles in cholinergic neurotransmission and neurodegenerative diseases.

A gene located on chromosome 3q26 codes for BuChE. Its region spans about 70 kb and has four exons and three introns. More than 40 mutations of BCHE have been recognized, but not all of them have been fully characterized. In general, these mutations manifest as different levels of catalytic activity. Normally, SCh is rapidly hydrolyzed after administration (the elimination half-time is estimated to be 2–4 minutes); however, when BuChE mutations are present SCh action may be prolonged. The duration of “suxamethonium apnea” cited for most common mutations ranges from 10 minutes to 2 hours; however, SCh effect may persist up to 8 hours and longer in some cases. Supportive ventilation is all that is required for treatment; there is no pharmacologic agent commonly used to increase the rate of recovery from abnormally prolonged SCh neuromuscular blockade.

Most variants of plasma BuChE can be variably inhibited by dibucaine and different phenotypical manifestations of BuChE deficiency have been studied by using dibucaine inhibition to differentiate among them. In normal patients, dibucaine will inhibit 80% of enzyme activity which corresponds to dibucaine number of 80. Heterozygous atypical plasma BuChE occurs in about 4% of the population with the corresponding dibucaine number between 30 and 65. Homozygous atypical plasma BuChE occurs in about 0.04% of the population and corresponds to a dibucaine number of 20. The most prevalent, wild-type BuChE is also inhibited by fluoride. However, there are two known less-prevalent fluoride-resistant forms of BuChE which allows for additional testing in cases of suspected clinical deficiency.

Plasma BuChE levels are affected by certain physiologic and pharmacologic factors. For example, alcoholism or obesity increase BuChE levels, so that higher doses of SCh may be necessary in obese patients, up to 1–2 mg/kg based on TBW and not IBW. BuChE levels may decrease to 75% of normal during pregnancy and to 67% of normal during immediate postpartum period; this degree of decrease is usually not clinically significant, but occasional prolonged apnea from SCh administration may result. Similarly, significant decrease of synthetic liver funciton may also result in prolonged apnea. In addition, plasma BuChE may be inhibited by exogenous compounds such as organophosphates (e.g., insecticides, chemical warfare agents, and echothiophate, a topical glaucoma agent), anticholinesterase agents (e.g., neostigmine, pyridostigmine, edrophonium), and MOAs.


  1. Sultan Darvesh, David A Hopkins, Changiz Geula Neurobiology of butyrylcholinesterase. Nat. Rev. Neurosci.: 2003, 4(2);131-8 PubMed Link
  2. D A Gorelick Enhancing cocaine metabolism with butyrylcholinesterase as a treatment strategy. Drug Alcohol Depend: 1997, 48(3);159-65 PubMed Link
  3. Charles W Schindler, Steven R Goldberg Accelerating cocaine metabolism as an approach to the treatment of cocaine abuse and toxicity. Future Med Chem: 2012, 4(2);163-75 PubMed Link