Rosenberry_1975_Proc.Natl.Acad.Sci.U.S.A_72_3834

Reference

Title : Catalysis by acetylcholinesterase: evidence that the rate-limiting step for acylation with certain substrates precedes general acid-base catalysis - Rosenberry_1975_Proc.Natl.Acad.Sci.U.S.A_72_3834
Author(s) : Rosenberry TL
Ref : Proceedings of the National Academy of Sciences of the United States of America , 72 :3834 , 1975
Abstract : Inferences about the catalytic mechanism of acetylcholinesterase (acetylcholine hydrolase, EC 3.1.1.7) are frequently made on the basis of a presumed analogy with chymotrypsin, EC 3.4.21.1. Although both enzymes are serine hydrolases, several differences in the steady-state kinetic properties of the two have been observed. In this report particular attention is focused on the second-order reaction constant, kcat/Kapp. While the reported pH dependence and deuterium oxide isotope effect associated with this parameter for chymotrypsin are generally consistent with simple models involving rate-limiting general acid-base catalysis, this study finds a more complicated situation with acetylcholinesterase. The apparent pKa of kcat/Kapp for acetylcholinesterase varies between 5.5 and 6.3 for neutral substrates and involves nonlinear inhibition by [H+]. Deuterium oxide isotope effects for kcat/Kapp range from 1.1 for acetylcholine to 1.9 for p-nitrophenyl acetate. The bimolecular reaction rate appears rate-limiting for acetylcholine at low concentrations, while a rate-limiting induced-fit step is proposed to account for apparent pKa values and low deuterium oxide isotope effects associated with low concentrations of phenyl acetate and isoamyl acetate.
ESTHER : Rosenberry_1975_Proc.Natl.Acad.Sci.U.S.A_72_3834
PubMedSearch : Rosenberry_1975_Proc.Natl.Acad.Sci.U.S.A_72_3834
PubMedID: 668

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Citations formats

Rosenberry TL (1975)
Catalysis by acetylcholinesterase: evidence that the rate-limiting step for acylation with certain substrates precedes general acid-base catalysis
Proceedings of the National Academy of Sciences of the United States of America 72 :3834

Rosenberry TL (1975)
Proceedings of the National Academy of Sciences of the United States of America 72 :3834