Esterase-Like Activity of Human Serum Albumin: Structure-Activity Relationships for the Reactions with Phenyl Acetates and p-Nitrophenyl Esters

Abstract

In order to investigate the reactivity of human serum albumin (HSA) with ester-type drugs and to characterize the site of the esterase-like activity, the Michaelis constants (Ks) and the catalytic rate constants (Kcat) were determined for the reactions of phenyl acetates and p-nitrophenyl esters with HSA at 25°. A linear relationship between log Kcat and Hammett σ values was found for phenyl acetates at pH 9.9; its slope was +1.52. It is suggested that aspirin also reacts with HSA by the same mechanism. The effects of aromatic substituents on the Ksvalues were small. The Ksvalues for p-nitrophenyl esters at pH 7.0 were correlated with Hansch's n and Taft's Esvalues as follows; log Ks= — 0.578 π- 0.184 Es—3.566 (r—0.963). The hydrophobic interaction was predominant in the binding of the substrates to HSA. The log kcat—pH profile obtained for p-nitrophenyl acetate indicates the participation of a single catalytic group, pKa=9.5, in this reaction. © 1979, The Pharmaceutical Society of Japan. All rights reserved.