Abstract

The single cysteine residue of human serum albumin (HSA-SH) is the most abundant plasma thiol. HSA transports fatty acids (FA), a cargo that increases under conditions of diabetes, exercise or adrenergic stimulation. The stearic acid-HSA (5/1) complex reacted sixfold faster than FA-free HSA at pH 7.4 with the disulfide 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB) and twofold faster with hydrogen peroxide and peroxynitrite. The apparent pK(a) of HSA-SH decreased from 7.9±0.1 to 7.4±0.1. Exposure to H(2)O(2) (2mM, 5min, 37°C) yielded 0.29±0.04mol of sulfenic acid (HSA-SOH) per mole of FA-bound HSA. The reactivity of HSA-SOH with low molecular weight thiols increased ∼threefold in the presence of FA. The enhanced reactivity of the albumin thiol at neutral pH upon FA binding can be rationalized by considering that the corresponding conformational changes that increase thiol exposure both increase the availability of the thiolate due to a lower apparent pK(a) and also loosen steric constraints for reactions. Since situations that increase circulating FA are associated with oxidative stress, this increased reactivity of HSA-SH could assist in oxidant removal.

Links

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Authors

Torres MJ, Turell L, Botti H, Antmann L, Carballal S, Ferrer-Sueta G, Radi R, Alvarez B

Institution

Laboratorio de Enzimología, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay.

Source

Archives of biochemistry and biophysics 521:1-2 2012 May pg 102-10

MeSH

Crystallography, X-Ray
Dithionitrobenzoic Acid
Fatty Acids
Humans
Hydrogen Peroxide
Hydrogen-Ion Concentration
Models, Molecular
Oxidation-Reduction
Protein Binding
Protein Stability
Serum Albumin
Sulfenic Acids
Sulfhydryl Compounds
Sulfhydryl Reagents

Pub Type(s)

In Vitro
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22450170