The thiol pool in human plasma: the central contribution of albumin to redox processes

Abstract

The plasma compartment has particular features regarding the nature and concentration of low and high molecular weight thiols and oxidized derivatives. Plasma is relatively poor in thiol-based antioxidants; thiols are in lower concentrations than in cells and mostly oxidized. The different thiol-disulfide pairs are not in equilibrium and the steady-state concentrations of total thiols as well as reduced versus oxidized ratios are maintained by kinetic barriers, including the rates of reactions and transport processes. The single thiol of human serum albumin (HSA-SH) is the most abundant plasma thiol. It is an important target for oxidants and electrophiles due to its reactivity with a wide variety of species and its relatively high concentration. A relatively stable sulfenic (HSA-SO3H) acid can be formed in albumin exposed to oxidants. Plasma increases in mixed disulfides (HSA-SSR) or in sulfinic (HSA-SO2H) and sulfonic (HSA-SO3H) acids are associated with different pathologies and may constitute biomarkers of the antioxidant role of the albumin thiol. In this work we provide a critical review of the plasma thiol pool with a focus on human serum albumin.

Keywords: 5,5′-dithiobis(2-nitrobenzoic acid); Albumin; DTNB; Free Radicals; GSH; HSA; HSA-SH; HSA-SO(2)H; HSA-SO(3)H; HSA-SOH; Mixed disulfides; Oxidants; Plasma; Sulfenic acid; Thiols; human serum albumin; reduced glutathione; sulfenic acid in human serum albumin; sulfinic acid in human serum albumin; sulfonic acid in human serum albumin; thiol of human serum albumin.

Fig. 1

Pathways of thiol oxidation. (a) Thiol-disulfide exchange reaction. (b) Two-electron oxidation of a thiol, yielding a sulfenic acid (RSOH) and subsequent reactions. (c) One-electron oxidation of a thiol, yielding a thiyl radical (RS^·) and subsequent reactions.

Fig. 2

Three-dimensional structure of human serum albumin, local environment and surface exposure of Cys34. (A) Cys34 is shown in green. (B) Thiol microenvironment: C, green; O, red; N, blue; S, yellow. (C) Surface exposure of Cys34. Atomic coordinates were downloaded from Protein Data Bank, Accession Code 4EMX. The figures were prepared using PyMOL v0.99 (www.pymol.org).