Modulation of the reactivity of the thiol of human serum albumin and its sulfenic derivative by fatty acids

Arch Biochem Biophys. 2012 May;521(1-2):102-10. doi: 10.1016/j.abb.2012.03.011. Epub 2012 Mar 19.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Crystallography, X-Ray
  • Dithionitrobenzoic Acid / metabolism
  • Dithionitrobenzoic Acid / pharmacology
  • Fatty Acids / metabolism
  • Fatty Acids / pharmacology*
  • Humans
  • Hydrogen Peroxide / metabolism
  • Hydrogen Peroxide / pharmacology
  • Hydrogen-Ion Concentration
  • In Vitro Techniques
  • Models, Molecular
  • Oxidation-Reduction
  • Protein Binding
  • Protein Stability
  • Serum Albumin / chemistry*
  • Serum Albumin / drug effects
  • Serum Albumin / metabolism
  • Sulfenic Acids / chemistry
  • Sulfenic Acids / metabolism
  • Sulfhydryl Compounds / chemistry
  • Sulfhydryl Compounds / metabolism
  • Sulfhydryl Reagents / metabolism
  • Sulfhydryl Reagents / pharmacology

Substances

  • Fatty Acids
  • Serum Albumin
  • Sulfenic Acids
  • Sulfhydryl Compounds
  • Sulfhydryl Reagents
  • Dithionitrobenzoic Acid
  • Hydrogen Peroxide