2 - The microenvironment of the sulfenic acid of human serum albumin: In search of clues for explaining its spontaneous decay

Abstract

Human serum albumin (HSA) is the most abundant protein in plasma. It consists of a single, non-glycosylated polypeptide chain of 585 residues. Only one free cysteine, namely Cys34, is present in HSA structure. With a concentration of ∼500 μM, Cys34 constitutes more than 80 % of the plasma free thiol pool. HSA has many functions, such as transporting small molecules, maintaining the oncotic pressure and scavenging oxidant/electrophilic species. The latter is associated with Cys34 thiol, hereto identified as HSA-SH. Reaction of HSA with a two-electron oxidant (e.g. H2O2, HOONO, HOCl) leads to formation of a sulfenic acid, HSA−SOH, with a relatively long half-life [1]. HSA−SOH can follow three possible destinations: (a) reaction with a free thiol (e.g. free Cys) to give a mixed disulfide (HSA-SS-R); (b) reaction with a two-electron oxidant to yield a sulfinic acid (HSA−SO2H); and (c) spontaneously decay to an uncharacterized product, named HSA−SX, with a rate constant of ca. 10−3 s−1 (37 °C, pH 7.4).[2]