Pseudocholinesterase

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Pseudocholinesterase
Pseudocholinesterase

Existing structure data: 1EHO , 1EHQ , 1KCJ , 1P0I , 1P0M , 1P0P , 1P0Q , 1XLU , 1XLV , 1XLW , 2J4C , 2PM8 , 2WID , 2WIF , 2WIG , 2WIJ , 2WIK , 2WIL , 2WSL , 2XMB , 2XMC , 2XMD , 2XMG , 2XQF , 2XQG , 2XQI , 2XQJ , 2XQK , 2Y1K , 3DJY , 3DKK , 3O9M , 4AQD , 4AXB , 4B0O , 4B0P , 4BBZ , 4BDS , 4TPK

Properties of human protein
Mass / length primary structure 574 amino acids
Secondary to quaternary structure Homotetramer
Identifier
Gene names BCHE  ; CHE1
External IDs
Enzyme classification
EC, category 3.1.1.8 ,  esterase
Response type Saponification
Substrate Acylcholine + H 2 O
Products Choline + carboxylate
Occurrence
Homology family Carboxylesterase
Parent taxon Chordates
Orthologue
human House mouse
Entrez 590 12038
Ensemble ENSG00000114200 ENSMUSG00000027792
UniProt P06276 Q03311
Refseq (mRNA) NM_000055 NM_009738
Refseq (protein) NP_000046 NP_033868
Gene locus Chr 3: 165.77 - 165.84 Mb Chr 3: 73.64 - 73.71 Mb
PubMed search 590 12038

The Pseudocholinesterase (also butyrylcholinesterase, BuChE) is an enzyme that the hydrolytic cleavage of the Esterbindung in choline esters catalyzed. It is therefore indispensable in the metabolism of chordates in addition to acetylcholinesterase for the breakdown of these substances. Mutations in the BCHE gene in humans can lead to the rare deficiency disease BCHE deficiency .

effect

Pseudocholinesterase is also capable of cleaving various esters that contain an alcohol component other than choline, such as aspirin, cocaine and heroin. It is inhibited by glycoalkaloids (alpha-solanine, alpha-chaconin), which are found in the green parts of the potato plant.

Occurrence

The enzyme occurs in many tissues, for example in the liver , in blood plasma , in the intestinal mucosa or in the pancreas ; it is believed to prevent acetylcholine from acting outside the synaptic gap.

Recent studies have shown that the detergent Triton X-100 , which is used in tissue reconditioning, inhibits pseudocholinesterase. As a result, the levels of this enzyme in many tissues have been underestimated.

Clinical significance

Pseudocholinesterase is important in connection with the use of muscle relaxants as part of general anesthesia. The short duration of action of the two relaxants mivacurium (non-depolarizing) and suxamethonium (depolarizing) is due to the rapid breakdown of the medicinal substances in the blood plasma (mivacurium in about 4 minutes, suxamethonium in about 1 minute half broken down). A deficiency in pseudocholinesterase (loss of enzyme activity> 75%, e.g. due to severe liver dysfunction, malignancies, pregnancy) or the presence of an atypical form of the enzyme (genetic, see below) leads to a delayed breakdown of these substances. Due to the resulting prolonged respiratory paralysis, the patient must be anesthetized and artificially ventilated (so-called post-ventilation) until the muscle-relaxing effect has subsided.

Several genetic variants of pseudocholinesterase are known, for example in entire population groups, due to frequent endogamy such as the Vaishya of the Indian castes of merchants, traders, moneylenders and large landowners. Homozygous persons for an atypical variant of the enzyme (frequency approx. 1: 2000) hydrolyze the above-mentioned muscle relaxants only slowly and the complications described can occur. The function of the enzyme is measured by determining the so-called dibucaine number in the blood serum ; In this test, the activity of the enzyme is determined after the addition of the local anesthetic dibucain .

See also

Individual evidence

  1. ↑ UniProt entry
  2. ↑ Darvesh, S. et al., Nat Rev Neurosci . 2003; 4 (2): 131-8
  3. ↑ Li, B. et al., J Neurochem. 2000 Sep; 75 (3): 1320-31
  4. ↑ Manoharan, I; Wieseler, S; Layer, PG; Lockridge, O; Boopathy, R (2006). "Naturally occurring mutation Leu307 Pro of human butyrylcholinesterase in the Vysya community of India". Pharmacogenetics and genomics 16 (7): 461-8. doi : 10.1097 / 01.fpc.0000197464.37211.77 . PMID 16788378 .