Physiological and pathological changes in the redox state of human serum albumin critically influence its binding properties

Abstract

Binding and transport of a number of endogenous and exogenous compounds is an important function of the main plasma protein, albumin. In vivo and in vitro, albumin may be oxidatively modified in different ways with different agents at different sites. These modifications have various consequences on the physiological functions of albumin. Diabetes mellitus, liver diseases and nephropathy are just a few examples of disorders in which oxidative stress is involved and altered albumin functions have been described. This review is focussed on the consequences of oxidative modification on the binding properties of albumin. These range from no effect to decreased or increased binding affinities depending on the ligand under investigation and the type of modification. Indicators for modification include glycosylation, disulphide formation or the content of carbonyl groups. The redox state of albumin can affect the binding properties in several ways, including altered conformation and consequently altered affinities at binding sites and altered binding when the binding reaction itself is redox sensitive. The physiological or pathophysiological concentrations of different oxidatively modified albumin molecules vary over a wide range and are crucial in assessing the clinical relevance of altered ligand binding properties of a particularly modified albumin species in various disease conditions.

Figure 1

Albumin binding sites: the structure of albumin is shown as strands using a PDB-file of Ghuman et al. (2005). Amino acids of the major binding sites I and II (according to Peters, 1996), Cys34 and Lys525 are depicted in space-filling representation. The ligand diazepam within site II is shown in light grey (PDB ID: 2BXF).

Figure 2

Major sulphur compounds in plasma: (a) reduced forms; (b) disulphides; (c), mixed disulphides; (d) higher oxidized forms of albumin (sulphenic acid, sulphinic acid, sulphonic acid, SNO-alb. Alb, albumin; Cys, cysteine; G, glutathione; HCys, homocysteine.