Thiol disulfide exchange reactions in human serum albumin: the apparent paradox of the redox transitions of Cys 34
Alessio Bocedia b, Giada Cattania b, Lorenzo Stellaa b, Renato Massoudc d, Giorgio Riccia b✉
- aDepartment of Chemical Sciences and Technologies University of Rome Tor Vergata Italy
- bDepartment of Chemical Sciences and Technologies, University of Rome Tor Vergata, Italy
- cDepartment of Experimental Medicine and Surgery University of Rome Tor Vergata Italy
- dDepartment of Experimental Medicine and Surgery, University of Rome Tor Vergata, Italy
- ✉Corresponding author
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Abstract
Human serum albumin (HSA) is characterized by 17 disulfides and by only one unpaired cysteine (Cys 34 ), 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 Cys 34 of HSA in their reactions with natural disulfides and thiols. Kinetic constants support the evidence that the Cys 34 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.
TL;DRKinetic 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, and give also a plausible explanation for the absence of involvement of the 17 disulfides naturally present in HSA in these redox transitions. (Semantic Scholar)