TY - JOUR
T1 - Butyrylcholinesterase, paraoxonase, and albumin esterase, but not carboxylesterase, are present in human plasma
AU - Li, Bin
AU - Sedlacek, Meghan
AU - Manoharan, Indumathi
AU - Boopathy, Rathnam
AU - Duysen, Ellen G.
AU - Masson, Patrick
AU - Lockridge, Oksana
N1 - Funding Information:
Supported by U.S. Army Medical Research and Materiel Command Grants DAMD17-01-1-0776 and DAMD17-01-2-0036 (to O.L.), UNMC Eppley Cancer Center Support Grant P30CA36727, U.S. Army Research, Development & Engineering Command Grant W911SR-04-C-0019 (to O.L.), French Office of the Defense Cooperation Attache Grant DGA/DSP/STTC PEA 03CO001 (to P.M.), and Indian funding agency, AICTE, New Delhi Grant F. No. 8019/RDII/BOR/R&D 226/2001 (to R.B.). MS was funded by the UNMC College of Medicine Dean's Office as a summer student. I.M. was funded by Bharathiar University Research Fellowship. The information does not necessarily reflect the position or the policy of the U.S., French, or Indian Government, and no official endorsement should be inferred.
PY - 2005/11/25
Y1 - 2005/11/25
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.
AB - 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.
KW - Acetylcholinesterase
KW - Albumin
KW - Aspirin
KW - Butyrylcholinesterase knockout mice
KW - Carboxylesterase
KW - Cocaine esterase
KW - Human plasma
KW - Irinotecan
KW - Mivacurium
KW - Paraoxonase
KW - Procaine
KW - Succinylcholine
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U2 - 10.1016/j.bcp.2005.09.002
DO - 10.1016/j.bcp.2005.09.002
M3 - Article
C2 - 16213467
AN - SCOPUS:27544478172
SN - 0006-2952
VL - 70
SP - 1673
EP - 1684
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
IS - 11
ER -