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Pseudo-enzymatic hydrolysis of 4-nitrophenyl acetate by human serum albumin: pH-dependence of rates of individual steps.

Biochem Biophys Res Commun. 2012 Jul 3;

Authors: Ascenzi P, Gioia M, Fanali G, Coletta M, Fasano M


Human serum albumin (HSA) displays esterase activity reflecting multiple irreversible chemical modifications rather than turnover. Here, kinetics of the pseudo-enzymatic hydrolysis of 4-nitrophenyl acetate (NphOAc) are reported. Under conditions where [HSA] ⩾ 5×[NphOAc] and [NphOAc] ⩾ 5×[HSA], the HSA-catalyzed hydrolysis of NphOAc is a first-order process for more than 95% of its course. From the dependence of the apparent rate constants k(app) and k(obs) on [HSA] and [NphOAc], respectively, values of K(s), k(+2), and k(+2)/K(s) were determined. Values of K(s), k(+2), and k(+2)/K(s) obtained at [HSA] ⩾ 5×[NphOAc] and [NphOAc] ⩾ 5×[HSA] are in good agreement, the deacylation step being rate limiting in catalysis. The pH dependence of k(+2)/K(s), k(+2), and K(s) reflects the acidic pK(a) shift of the Tyr411 catalytic residue from 9.0±0.1 in the substrate-free HSA to 8.1±0.1 in the HSA:NphOAc complex. Accordingly, diazepam inhibits competitively the HSA-catalyzed hydrolysis of NphOAc by binding to Tyr411.

PMID: 22771811 [PubMed - as supplied by publisher]