Thiol disulfide exchange reactions in human serum albumin: the apparent paradox of the redox transitions of Cys34. (2nd August 2018)

• Record Type: Journal Article
• Authors: Bocedi, Alessio; Cattani, Giada; Stella, Lorenzo; Massoud, Renato; Ricci, Giorgio
• Is Part Of: FEBS journal. Volume 285:Number 17(2018)
• Page Start: 3225
• Page End: 3237
• Publication Date: 2018-08-02
• Subjects: Cys34 of human serum albumin -- disulfide stability in albumin -- oxidative stress -- oxidized albumin -- redox transitions in albumin; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pathology, Molecular -- Periodicals; 572
• DOI: 10.1111/febs.14609
• Languages: English
• ISSNs: 1742-464X

Abstract

Abstract : Human serum albumin (HSA) is characterized by 17 disulfides and by only one unpaired cysteine (Cys34 ), which can be free in the reduced albumin or linked as a mixed disulfide with cysteine, or in minor amount with other natural thiols, in the oxidized albumin. In healthy subjects, the level of the oxidized form is about 35%, but it rises up to 70% after oxidative insults or in patients with kidney diseases. Oxidized albumin is therefore considered a short‐term biomarker of oxidative stress as its level may increase or decrease under appropriate redox inputs in discrete temporal spans. This paper defines, for the first time, the kinetic properties of reduced and oxidized Cys34 of HSA in their reactions with natural disulfides and thiols. Kinetic constants support the evidence that the Cys34 redox oscillations observed in vivo are mainly due to the interaction with cysteine and cystine without the involvement of any enzymatic support. This study gives also a plausible explanation for the absence of involvement of the 17 disulfides naturally present in HSA in these redox transitions. This inert behavior toward cysteine is marginally due to solvent accessibility or flexibility factors of these bonds but mainly to their strong thermodynamic stability, which is caused essentially by a proximity effect. A similar mechanism is likely at play in the many proteins that maintain disulfide bridges in a reducing medium like the cytosol. Abstract : Human serum albumin shows 17 disulfides and one unpaired Cys34 which can be free in the reduced albumin or linked as a mixed disulfide in the oxidized albumin. Kinetic constants support the evidence that the Cys34 redox oscillations observed in vivo are mainly due to the interaction with cysteine and cystine without the involvement of any enzymatic support.