title: Modulation of the reactivity of the thiol of human serum albumin and its sulfenic derivative by fatty acids.
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.
authors.affiliation: Laboratorio de Enzimología, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay.
authors.forename: María José
authors.initials: MJ
authors.lastname: Torres
authors.forename: Lucía
authors.initials: L
authors.lastname: Turell
authors.forename: Horacio
authors.initials: H
authors.lastname: Botti
authors.forename: Laura
authors.initials: L
authors.lastname: Antmann
authors.forename: Sebastián
authors.initials: S
authors.lastname: Carballal
authors.forename: Gerardo
authors.initials: G
authors.lastname: Ferrer-Sueta
authors.forename: Rafael
authors.initials: R
authors.lastname: Radi
authors.forename: Beatriz
authors.initials: B
authors.lastname: Alvarez
mesh_terms: D018360:Crystallography, X-Ray; D004228:Dithionitrobenzoic Acid / Q000378:metabolism / Q000494:pharmacology; D005227:Fatty Acids / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008958:Models, Molecular; D010084:Oxidation-Reduction; D011485:Protein Binding; D055550:Protein Stability; D012709:Serum Albumin / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D013434:Sulfenic Acids / Q000737:chemistry / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000737:chemistry / Q000378:metabolism; D013439:Sulfhydryl Reagents / Q000378:metabolism / Q000494:pharmacology
chemical_list: D005227:Fatty Acids; D012709:Serum Albumin; D013434:Sulfenic Acids; D013438:Sulfhydryl Compounds; D013439:Sulfhydryl Reagents; D004228:Dithionitrobenzoic Acid; D006861:Hydrogen Peroxide