Alteration of human serum albumin binding properties induced by modifications: A review

https://doi.org/10.1016/j.saa.2017.05.023Get rights and content

Highlights

  • Human serum albumin binding properties can be induced by modifications.

  • Glycation, oxidation and ageing are the most popular albumin modifications.

  • Modification of albumin influences on its physiological functions

Abstract

Albumin, a major transporting protein in the blood, is the main target of modification that affects the binding of drugs to Sudlow's site I and II. These modification of serum protein moderates its physiological function, and works as a biomarker of some diseases. The main goal of the paper was to explain the possible alteration of human serum albumin binding properties induced by modifications such as glycation, oxidation and ageing, their origin, methods of evaluation and positive and negative meaning described by significant researchers.

Introduction

Human serum albumin (HSA) is well known multifunctional protein in the intravascular compartment. Its main function is a transport of many endo- and exogenous compounds like drugs, steroids, fatty acids and thyroid hormones [1]. HSA, is organized in I, II and III domains and A and B subdomains. It contains single polypeptide chain of 585 amino acids containing i.e. 17 tyrosil residues and one tryptophan – Trp-214. HSA owns 35 cysteine residues, where 34 form intramolecular disulfide bonds. A single thiol, free Cys-34, constitutes almost 80% of the all thiol groups in plasma. Because Cys-34 is located in subdomain IA, it is probable that plays an important role in drugs binding. For HSA two major drug specific binding sites have been identified – Sudlow's site I and site II [2]. Site I is found in subdomain IIA while site II in IIIA [3]. It is noteworthy that drugs binding with serum proteins (i.e. albumin) is involved not only in the pharmacological effects of a drug but also in its pharmacokinetics.

A main protein in the blood, albumin, is the main goal of chemical stresses during physiological states like oxidative stress occurring in the ageing degenerative diseases (Alzheimer's and Parkinson's disease), and glucose stress in diabetes mellitus [4], [5]. Because glycation and oxidation co-occur with each other, reinforcing negative effects, therefore they are referred to common name – glycoxidative processes [6]. In vivo and in vitro studies of albumin and other proteins oxidation and glycation allowed to identify markers used in the diagnosis and monitoring of diseases. From the recent studies it has become obvious that these modifications have an influence on albumin actions and impact on functioning of cell. In addition long lasting glycoxidative processes lead to the isomerization to aged form of serum albumin and formation of aggregates. Both, the ageing process and interactions of ligands with proteins induce variations in the properties of the macromolecules. This phenomenon modifies the biological activities and conformations of albumin and contributes to the appearance of unexpected abilities [7]. It is noteworthy that the reduction in serum albumin biological activity has a medical significance, because it affects drug metabolism and particularly drug tolerance in the elderly [8].

Large amounts of spectral data that contain useful information concerning albumin modification are usually obtained from different analytical techniques including chromatography, spectrometry, spectrophotometry [9], spectroscopy [10], etc. The present paper describes based on the literature the albumin modification, its influence on albumin physiological functions and practical use of modified proteins.

Section snippets

Modification of Human Serum Albumin by Oxidation

Oxidation, glycation and S-nitrosylation are the major posttranslational modifications of albumin [11]. These modifications are distributed to the body through the circulatory system and albumin oxidized forms increases with the increase of pathophysiological states [12]. According to Scopus database, oxidative modification since more than 30 years are the subject of over than hundred researches. Works that described chemical modifications of various amino acid residues in BSA appeared in the

Modification of Human Serum Albumin by Glycation

Major modification concerning HSA is a significant multistage chemical process known as non-enzymatic glycation – Maillard reaction. Glycation of HSA influences its stability, activity as well as its physical and chemical properties, thus affecting the functions performed by this protein [59]. The early stage of glycation is an impulsive reaction of condensation between reducing sugars and a free amine group (ε-amino group of lysine, arginine or N-terminal amino group of protein) [60], [61],

Modification of Human Serum Albumin by Ageing

Ageing and connected diseases have recently become a significant social problem. Ageing processes may be accelerated because of accumulation of toxic and harmful metabolic products. The old age has no effect on α-acid glycoprotein (AAG) concentration, whereas plasma albumin level decreases as a function of age in both sexes. Veering et al. observed no variances between males and females in the plasma concentrations of HSA and AAG at older organisms [116]. Cabrerizo et al. noticed that

Conclusions

The loss of biological activity of human serum albumin affects drug metabolism and particularly drug tolerance in the elderly. The present paper briefly describes based on the literature the most popular albumin modifications. These information led us to concluded that changes in albumin structure alter its binding properties that influence on physiological functions as well as can be used as a biomarker of many diseases.

Acknowledgment

This work was supported by grants from the Medical University of Silesia KNW-1-034/K/6/O.

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      PAEs can remain in the environment for hundreds of years due to their chemical properties; hence, the toxicological mechanism of PAEs for humans should be paid more attention. Human serum albumin (HSA) is the most copious protein in plasma, which performs wide-ranging physiological functions, including transportation, binding, and maintaining the perfusion colloid osmotic pressure of blood (Maciazek-Jurczyk et al., 2018; Rabbani and Ahn, 2019; Zhu et al., 2018a). As the principal depot of small molecules in blood, in the dissociative state, HSA can bind with ligands and form ligand-HSA complexes.

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