title: Noncovalent interactions of long-chain perfluoroalkyl acids with serum albumin.
abstract: Preferential distribution of long-chain perfluoroalkyl acids (PFAAs) in the liver, kidney, and blood of organisms highlights the importance of PFAA-protein interactions in PFAA tissue distribution patterns. A serum protein association constant may be a useful parameter to characterize the bioaccumulative potential and in vivo bioavailability of PFAAs. In this work, association constants (K(a)) and binding stoichiometries for PFAA-albumin complexes are quantified over a wide range of PFAA:albumin mole ratios. Primary association constants for perfluorooctanoate (PFOA) or perfluorononanoate (PFNA) with the model protein bovine serum albumin (BSA) determined via equilibrium dialysis are on the order of 10(6) M(-1) with one to three primary binding sites. PFNA was greater than 99.9% bound to BSA or human serum albumin (HSA) at a physiological PFAA:albumin mole ratio (<10(-3)), corresponding to a high protein-water distribution coefficient (log K(PW) > 4). Nanoelectrospray ionization mass spectrometry (nanoESI-MS) data reveal PFAA-BSA complexes with up to eight occupied binding sites at a 4:1 PFAA:albumin mole ratio. Association constants estimated by nanoESI-MS are on the order of 10(5) M(-1) for PFOA and PFNA and 10(4) M(-1) for perfluorodecanoate and perfluorooctanesulfonate. The results reported here suggest binding through specific high affinity interactions at low PFAA:albumin mole ratios.
authors.affiliation: Department of Civil and Environmental Engineering, Stanford University, Stanford, California 94305, USA.
authors.forename: Heather N
authors.initials: HN
authors.lastname: Bischel
authors.forename: Laura A
authors.initials: LA
authors.lastname: Macmanus-Spencer
authors.forename: Richard G
authors.initials: RG
authors.lastname: Luthy
mesh_terms: D017738:Alkanesulfonic Acids / Q000032:analysis*; D000818:Animals; D001665:Binding Sites; D001682:Biological Availability; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D005466:Fluorocarbons / Q000032:analysis*; D006801:Humans; D007700:Kinetics; D008024:Ligands; D036103:Nanotechnology / Q000379:methods; D011485:Protein Binding; D012709:Serum Albumin / Q000737:chemistry*; D012710:Serum Albumin, Bovine / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D014018:Tissue Distribution
chemical_list: D017738:Alkanesulfonic Acids; D005466:Fluorocarbons; D008024:Ligands; D012709:Serum Albumin; D012710:Serum Albumin, Bovine; C076994:perfluorooctane sulfonic acid