Esterases

Oksana Lockridge, D. M. Quinn, Z. Radić

Research output: Chapter in Book/Report/Conference proceedingChapter

1 Citation (Scopus)

Abstract

This structurally, mechanistically, and functionally diverse family of enzymes is found in nearly all human tissues where they hydrolyze physiologically essential esters, drugs, and toxins. Several esterases are found in human blood: butyrylcholinesterase and paraoxonase in plasma and acetylcholinesterase, esterase D (ESD), and neuropathy target esterase in blood cells. In contrast to rodents, human plasma contains no carboxylesterase. Human red blood cells contain glycolipid-anchored acetylcholinesterase outside and ESD inside the cells. Liver, lung, intestine, and other tissues contain a total of 31 esterases including 4 carboxylesterases, 2 paraoxonases, 14 thioesterases, 6 lipases, 2 cholinesterases, 1 methylesterase, 1 platelet-activating factor acetylhydrolase, and 1 sialate O-acetylesterase. Esterases detoxicate cocaine, organophosphorus pesticides, pyrethroid insecticides, nerve agents, succinylcholine, mivacurium, ritalin, aspirin, esmolol, and demerol. The prodrugs irinotecan, bambuterol, Tamiflu, trandolapril, imidapril, temocapril, and ciclesonide are converted into active drugs by esterases. Genetic variants of human butyrylcholinesterase, carboxylesterase, paraoxonase, and ESD affect the metabolism of ester drugs. A His322 to Asn mutation in human acetylcholinesterase has no effect on catalytic activity but does define an YT2 blood group antibody epitope. Catalytic triad (Ser-His-Glu/Asp) of butyrylcholinesterase, acetylcholinesterase, carboxylesterase, and ESD is covalently inhibited by organophosphates rendering nerve agents and organophosphorus pesticides acutely toxic primarily due to inhibition of acetylcholinesterase. The serine esterases have similar tertiary, alpha/beta hydrolase fold protein structures different from six-bladed beta-propeller structure of paraoxonase.

Original languageEnglish (US)
Title of host publicationBiotransformation
PublisherElsevier Inc.
Pages277-307
Number of pages31
Volume10-15
ISBN (Electronic)9780081006122
ISBN (Print)9780081006016
DOIs
StatePublished - Jan 1 2018

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Esterases
Acetylcholinesterase
Butyrylcholinesterase
Aryldialkylphosphatase
Carboxylesterase
irinotecan
trandolapril
Pesticides
Esters
Carboxylic Ester Hydrolases
Essential Drugs
Oseltamivir
Pyrethrins
Meperidine
Methylphenidate
Succinylcholine
Organophosphates
Poisons
Platelet Activating Factor
Glycolipids

Keywords

  • Acetylcholinesterase
  • Alpha/beta hydrolase fold
  • Butyrylthiocholine
  • Carboxylesterase
  • Detoxication
  • Esterase D
  • Nerve agents
  • Organophosphorus pesticides
  • Paraoxonase
  • Prodrug activation

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Lockridge, O., Quinn, D. M., & Radić, Z. (2018). Esterases. In Biotransformation (Vol. 10-15, pp. 277-307). Elsevier Inc.. https://doi.org/10.1016/B978-0-12-801238-3.01970-X

Esterases. / Lockridge, Oksana; Quinn, D. M.; Radić, Z.

Biotransformation. Vol. 10-15 Elsevier Inc., 2018. p. 277-307.

Research output: Chapter in Book/Report/Conference proceedingChapter

Lockridge, O, Quinn, DM & Radić, Z 2018, Esterases. in Biotransformation. vol. 10-15, Elsevier Inc., pp. 277-307. https://doi.org/10.1016/B978-0-12-801238-3.01970-X
Lockridge O, Quinn DM, Radić Z. Esterases. In Biotransformation. Vol. 10-15. Elsevier Inc. 2018. p. 277-307 https://doi.org/10.1016/B978-0-12-801238-3.01970-X
Lockridge, Oksana ; Quinn, D. M. ; Radić, Z. / Esterases. Biotransformation. Vol. 10-15 Elsevier Inc., 2018. pp. 277-307
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