Aprophen: A Substrate and Inhibitor of Butyrylcholinesterase and Carboxylesterases

摘要

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 kinetic were observed; an apparent competitive inhibition constant was estimated to be .00000037M. BuChE hydrolysis of aprophen to diphenylptopionic acid and diethylaminoethanol did not appear to follow Michaelis-Menten kinetics. The BuChE turnover number for aprophen is .002/sec. Rabbit liver oligomeric and monoeric carboxylesterases)CE) also hydorlyze aprophen with a similar turnover number that varied from .0014/sec to .00043/sec. respectively. Comparison of the catalytic rate of aprophen hydrolysis with butyrylthiocholine (BTC) and the neutral aromatic substrate, phenylthiobutyrate(phiTB), indicated that BuChE hydroyzes BTC and phiTB 320,000 times more rapidly than aprophen, respectively.