Butyrylcholinesterase, paraoxonase, and albumin esterase, but not carboxylesterase, are present in human plasma

Bin Li, Meghan Sedlacek, Indumathi Manoharan, Rathnam Boopathy, Ellen G. Duysen, Patrick Masson, Oksana Lockridge

Research output: Contribution to journalArticle

355 Citations (Scopus)

Abstract

The goal of this work was to identify the esterases in human plasma and to clarify common misconceptions. The method for identifying esterases was nondenaturing gradient gel electrophoresis stained for esterase activity. We report that human plasma contains four esterases: butyrylcholinesterase (EC 3.1.1.8), paraoxonase (EC 3.1.8.1), acetylcholinesterase (EC 3.1.1.7), and albumin. Butyrylcholinesterase (BChE), paraoxonase (PON1), and albumin are in high enough concentrations to contribute significantly to ester hydrolysis. However, only trace amounts of acetylcholinesterase (AChE) are present. Monomeric AChE is seen in wild-type as well as in silent BChE plasma. Albumin has esterase activity with alpha- and beta-naphthylacetate as well as with p-nitrophenyl acetate. Misconception #1 is that human plasma contains carboxylesterase. We demonstrate that human plasma contains no carboxylesterase (EC 3.1.1.1), in contrast to mouse, rat, rabbit, horse, cat, and tiger that have high amounts of plasma carboxylesterase. Misconception #2 is that lab animals have BChE but no AChE in their plasma. We demonstrate that mice, unlike humans, have substantial amounts of soluble AChE as well as BChE in their plasma. Plasma from AChE and BChE knockout mice allowed identification of AChE and BChE bands without the use of inhibitors. Human BChE is irreversibly inhibited by diisopropylfluorophosphate, echothiophate, and paraoxon, but mouse BChE spontaneously reactivates. Since human plasma contains no carboxylesterase, only BChE, PON1, and albumin esterases need to be considered when evaluating hydrolysis of an ester drug in human plasma.

Original languageEnglish (US)
Pages (from-to)1673-1684
Number of pages12
JournalBiochemical Pharmacology
Volume70
Issue number11
DOIs
StatePublished - Nov 25 2005

Fingerprint

Plasma (human)
Butyrylcholinesterase
Aryldialkylphosphatase
Carboxylesterase
Esterases
Albumins
Acetylcholinesterase
Plasmas
Hydrolysis
Esters
Paraoxon
Isoflurophate
Tigers
Cholinesterases
Electrophoresis
Knockout Mice
Rats
Horses
Animals
Gels

Keywords

  • Acetylcholinesterase
  • Albumin
  • Aspirin
  • Butyrylcholinesterase knockout mice
  • Carboxylesterase
  • Cocaine esterase
  • Human plasma
  • Irinotecan
  • Mivacurium
  • Paraoxonase
  • Procaine
  • Succinylcholine

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

Cite this

Butyrylcholinesterase, paraoxonase, and albumin esterase, but not carboxylesterase, are present in human plasma. / Li, Bin; Sedlacek, Meghan; Manoharan, Indumathi; Boopathy, Rathnam; Duysen, Ellen G.; Masson, Patrick; Lockridge, Oksana.

In: Biochemical Pharmacology, Vol. 70, No. 11, 25.11.2005, p. 1673-1684.

Research output: Contribution to journalArticle

Li, Bin ; Sedlacek, Meghan ; Manoharan, Indumathi ; Boopathy, Rathnam ; Duysen, Ellen G. ; Masson, Patrick ; Lockridge, Oksana. / Butyrylcholinesterase, paraoxonase, and albumin esterase, but not carboxylesterase, are present in human plasma. In: Biochemical Pharmacology. 2005 ; Vol. 70, No. 11. pp. 1673-1684.
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AU - Manoharan, Indumathi

AU - Boopathy, Rathnam

AU - Duysen, Ellen G.

AU - Masson, Patrick

AU - Lockridge, Oksana

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N2 - The goal of this work was to identify the esterases in human plasma and to clarify common misconceptions. The method for identifying esterases was nondenaturing gradient gel electrophoresis stained for esterase activity. We report that human plasma contains four esterases: butyrylcholinesterase (EC 3.1.1.8), paraoxonase (EC 3.1.8.1), acetylcholinesterase (EC 3.1.1.7), and albumin. Butyrylcholinesterase (BChE), paraoxonase (PON1), and albumin are in high enough concentrations to contribute significantly to ester hydrolysis. However, only trace amounts of acetylcholinesterase (AChE) are present. Monomeric AChE is seen in wild-type as well as in silent BChE plasma. Albumin has esterase activity with alpha- and beta-naphthylacetate as well as with p-nitrophenyl acetate. Misconception #1 is that human plasma contains carboxylesterase. We demonstrate that human plasma contains no carboxylesterase (EC 3.1.1.1), in contrast to mouse, rat, rabbit, horse, cat, and tiger that have high amounts of plasma carboxylesterase. Misconception #2 is that lab animals have BChE but no AChE in their plasma. We demonstrate that mice, unlike humans, have substantial amounts of soluble AChE as well as BChE in their plasma. Plasma from AChE and BChE knockout mice allowed identification of AChE and BChE bands without the use of inhibitors. Human BChE is irreversibly inhibited by diisopropylfluorophosphate, echothiophate, and paraoxon, but mouse BChE spontaneously reactivates. Since human plasma contains no carboxylesterase, only BChE, PON1, and albumin esterases need to be considered when evaluating hydrolysis of an ester drug in human plasma.

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KW - Irinotecan

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KW - Paraoxonase

KW - Procaine

KW - Succinylcholine

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