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.

Glycated Albumin With Loss of Fatty Acid Binding Capacity Contributes to Enhanced Arachidonate Oxygenation and Platelet Hyperactivity: Relevance in Patients With Type 2 Diabetes

“…However, though the effects of high levels of total plasma NEFAs have been studied (10,11,61), the putative deterioration in the NEFA binding capacity of albumin was not addressed in a systematic way. In previous studies, it was reported that oxidative stress and glycation caused conformational changes in albumin structure (14,29,62) with possible effects in vitro on platelet function (17,63,64). The novelty of the current study is the demonstration that glycation probably impairs the binding properties of albumin of patients with T2D.…”

Serum Albumin Concentration and Cognitive Impairment

“…[26] Serum albumin plays a vital role in the binding of drugs, hormones, iron and free fatty acids, and reduced levels may contribute to cognitive impairment resulting from toxicity. [27] Albumin also inhibits the formation of amyloid beta-peptide fibrils, [28] and low levels of albumin in the brain and cerebrospinal fluid may therefore lead to increased Alzheimer's type pathology. [29] While serum albumin levels may lead to cognitive impairment, reverse causality is also possible, and cognitive impairment may result in lowered serum albumin.…”

Detection of picomolar concentrations of lead in water using albumin-based fluorescence sensor

“…1͒, comes from two aromatic residues of tyrosine ͑Tyr͒ and tryptophan ͑Trp͒ located in subdomain IIIA and 214th residue of subdomain IIA, respectively. 15,16 No other fluorescence emission is observed other than a weak Raman signal from water at around 3400 cm −1 with respect to the excitation wavelength, which was always present and could be, if needed, digitally removed from those spectra. Next, the albumin solution was treated with leadcontaining solution starting from 1 pM ͑10 −12 M͒ concentration.…”