Substrate activation of butyrylcholinesterase and substrate inhibition of acetylcholinesterase by 3,3-dimethylbutyl-N-n-butylcarbamate and 2-trimethylsilyl-ethyl-N-n-butylcarbamate.
Carbamates are used to treat Alzheimer's disease. These compounds inhibit acetylcholinesterase and butyrylcholinesterase. The goal of this work is to use the substrate analogs of butyrylcholinesterase, 3,3-dimethylbutyl-N-n-butylcarbamate (1) and 2-trimethylsilyl-ethyl-N-n-butylcarbamate (2) to probe the substrate activation mechanism of butyrylcholinesterase. Compounds 1 and 2 are characterized as the pseudo substrate inhibitors of acetylcholinesterase; however, compounds 1 and 2 are characterized as the essential activators of butyrylcholinesterase. Therefore, compounds 1 and 2 mimic the substrate in the acetylcholinesterase-catalyzed reactions, but the behavior of compounds 1 and 2 mimics the substrate activation in the butyrylcholinesterase-catalyzed reactions.
Chiou
Shyh-Ying
SY
Institute of Medicine and Division of Neurosurgery, Chung-Shan Medical University Hospital, Taichung 402, Taiwan.
Wu
Yon-Gi
YG
Lin
Yan-Fu
YF
Lin
Long-Yau
LY
Lin
Gialih
G
D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D002091:Butyrylcholinesterase / Q000378:metabolism*; D002219:Carbamates / Q000737:chemistry / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D006736:Horses; D007700:Kinetics; D016018:Least-Squares Analysis; D008954:Models, Biological; D013379:Substrate Specificity / Q000187:drug effects; D014297:Trimethylsilyl Compounds / Q000737:chemistry / Q000494:pharmacology*
C524208:2-trimethylsilylethyl-N-n-butylcarbamate; C524207:3,3-dimethylbutyl-N-n-butylcarbamate; D002219:Carbamates; D002800:Cholinesterase Inhibitors; D014297:Trimethylsilyl Compounds; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase