Butyrylcholinesterase: inhibition by arsenite, fluoride, and other ligands, cooperativity in binding

JD Page, IB Wilson and I Silman

Arsenite is a quasi-irreversible inhibitor of human serum butyrylcholinesterase with a dissociation constant of 0.129 mM at pH 7.4, 25 degrees, 0.067 M phosphate, mu = 0.17 M. The inhibition process is second order with a rate constant of 340 M-1 min-1. The first order rate of dissociation, 0.044 min-1, is unaffected by fluoride but is decreased by substrate. The binding of arsenite and fluoride, as determined by the effect of fluoride on the apparent arsenite-enzyme dissociation constant, is highly anticooperative and may be mutually exclusive. The fluoride-enzyme dissociation constant determined from these experiments is 0.90 mM. The binding of a number of other substances, such as dibucaine, is markedly anticooperative with arsenite binding. The binding of some of these substances is positively cooperative with fluoride binding. The effect can be large; procainamide binds 17 times more strongly in the presence of fluoride. Similarly, the mutual binding of benzoylcholine as substrate and fluoride is cooperative, 30-fold, butyrylthiocholine and fluoride, 21- fold, propionylthiocholine and fluoride, 8.3-fold, and acetylthiocholine and fluoride, only 1.8-fold.

Volume 27, Issue 4, pp. 437-443, 04/01/1985
Copyright © 1985 by American Society for Pharmacology and Experimental Therapeutics

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