Monoclonal antibody AE-2 modulates carbamate and organophosphate inhibition of fetal bovine serum acetylcholinesterase.
The monoclonal antibody AE-2, raised against the human erythrocyte acetylcholinesterase (AChE) dimer (acetylcholine acetylhydrolase, EC 3.1.1.7), binds to other mammalian AChEs, including the tetramer that occurs in fetal bovine serum (FBS). AE-2 partially inhibited the rate of hydrolysis of the charged substrate acetylthiocholine by FBS AChE, whereas it increased the rate of hydrolysis of the neutral substrate indophenyl acetate. Present results show that AE-2 decreases the rate of inhibition of FBS AChE by the positively charged organophosphate amiton-p-toluene sulfonate and the positively charged carbamates pyridostigmine and neostigmine but accelerates inhibition of FBS AChE by the neutral organophosphates paraoxon and diisopropylfluorophosphate. Results suggest that AE-2 may allosterically modulate an anionic site in the catalytic center of FBS AChE.
Wolfe
A D
AD
Division of Biochemistry, Walter Reed Army Institute of Research, Washington, D.C. 20307-5100.
Chiang
P K
PK
Doctor
B P
BP
Fryar
N
N
Rhee
J P
JP
Saeed
M
M
D000110:Acetylcholinesterase / Q000097:blood / Q000502:physiology*; D000122:Acetylthiocholine / Q000378:metabolism; D000494:Allosteric Regulation; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002219:Carbamates; D002417:Cattle; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D005333:Fetus; D006868:Hydrolysis; D007215:Indophenol / Q000031:analogs & derivatives / Q000378:metabolism; D007306:Insecticides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007700:Kinetics; D009943:Organophosphorus Compounds
D000911:Antibodies, Monoclonal; D002219:Carbamates; D002800:Cholinesterase Inhibitors; D007306:Insecticides; D009943:Organophosphorus Compounds; D000122:Acetylthiocholine; D007215:Indophenol; C016519:indophenyl acetate; D000110:Acetylcholinesterase