Aprophen: a substrate and inhibitor of butyrylcholinesterase and carboxylesterases.
Biochem Pharmacol
; 34(12): 2063-8, 1985 Jun 15.
Article
en En
| MEDLINE
| ID: mdl-4004924
Aprophen, alpha-methyl-alpha-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 X 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 X 10(-3) sec-1. Rabbit liver oligomeric and monomeric carboxylesterases (CE) also hydrolyzed aprophen with a similar turnover number that varied from 1.4 X 10(-3) sec-1 to 4.3 X 10(-4) sec-1 respectively. Comparison of the catalytic rate of aprophen hydrolysis with butyrylthiocholine (BTC) and the neutral aromatic substrate, phenylthiobutyrate (phi TB), indicated that BuChE hydrolyzed BTC and phi TB 3.2 X 10(5) and 3.1 X 10(5) times more rapidly than aprophen respectively. Similarly, the CEs also hydrolyzed BTC and phi TB 17.6 and 1.9 X 10(5) times 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.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Parasimpatolíticos
/
Fenilpropionatos
/
Butirilcolinesterasa
/
Hidrolasas de Éster Carboxílico
/
Inhibidores de la Colinesterasa
/
Colinesterasas
Límite:
Humans
Idioma:
En
Revista:
Biochem Pharmacol
Año:
1985
Tipo del documento:
Article
Pais de publicación:
Reino Unido