Aprophen: a substrate and inhibitor of butyrylcholinesterase and carboxylesterases
| Autor: | J S Ralston, R S Rush, Alan D. Wolfe |
|---|---|
| Rok vydání: | 1985 |
| Předmět: |
Pharmacology
Chromatography biology Phenylpropionates Chemistry Hydrolysis Substrate (chemistry) Parasympatholytics Biochemistry Medicinal chemistry Turnover number Butyrylthiocholine Kinetics Non-competitive inhibition Enzyme inhibitor Butyrylcholinesterase biology.protein Cholinesterases Humans Cholinesterase Inhibitors Carboxylic Ester Hydrolases Cholinesterase |
| Zdroj: | Biochemical pharmacology. 34(12) |
| ISSN: | 0006-2952 |
| Popis: | Aprophen, α-methyl-α-phenylbenzeneacetic acid-2-(diethylamino) ethyl ester, is a potent reversible inhibitor and a poor substrate of human serum butyrylcholinesterase (BuChE). Complex mixed competitive noncompetitive inhibition kinetics were observed; an apparent competitive inhibition constant was estimated to be 3.7 × 10 −7 M. BuChE hydrolysis of aprophen to diphenylpropionic acid and diethylaminoethanol did not appear to follow Michaelis-Menten kinetics. The BuChE turnover number for aprophen was 2.0 × 10 −3 sec −1 . Rabbit liver oligomeric and monomeric carboxylesterases (CE) also hydrolyzed aprophen with a similar turnover number that varied from 1.4 × 10 −3 sec −1 to 4.3 × 10 −4 sec −1 respectively. Comparison of the catalytic rate of aprophen hydrolysis with butyrylthiocholine (BTC) and the neutral aromatic substrate, phenylthiobutyrate (φTB), indicated that BuChE hydrolyzed BTC and φTB 3.2 × 10 5 and 3.1 × 10 5 times more rapidly than aprophen respectively. Similarly, the CEs also hydrolyzed BTC and φTB 17.6 and 1.9 × 10 5 times more rapidly than aprophen. Acetylcholinesterases from bovine erythrocyte and electric eel were not inhibited by aprophen nor was aprophen hydrolyzed by these enzymes. The hydrolysis and inhibition reactions may best be described by a complex reaction scheme involving multiple binding sites for both the substrate and the inhibitor as well as positive cooperative ligand binding. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|