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 (k_cat) were determined for the reactions of phenyl acetates and p-nitrophenyl esters with HSA at 25°. A linear relationship between log k_cat 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 K_s values were small. The K_s values for p-nitrophenyl esters at pH 7.0 were correlated with Hansch's π and Taft's E_s values as follows ; log K_s=-0.578 π-0.184 E_s-3.566 (γ=0.963). The hydrophobic interaction was predominant in the binding of the substrates to HSA. The log k_cat-pH profile obtained for p-nitrophenyl acetate indicates the participation of a single catalytic group, pK_a≒9.5, in this reaction.