Noncovalent Interactions of Long-Chain Perfluoroalkyl Acids with Serum Albumin

• Published in: Environmental science & technology Vol. 44; no. 13; pp. 5263 - 5269
• Main Authors: Bischel, Heather N, MacManus-Spencer, Laura A, Luthy, Richard G
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 01.07.2010
• Subjects: Alkanesulfonic Acids - analysis; Animals; Binding Sites; Bioavailability; Biological Availability; Cattle; Dose-Response Relationship, Drug; Ecotoxicology and Human Environmental Health; Fluorocarbons - analysis; Humans; Kinetics; Ligands; Mass spectrometry; Nanotechnology - methods; Protein Binding; Proteins; Serum Albumin - chemistry; Serum Albumin, Bovine - chemistry; Spectrometry, Mass, Electrospray Ionization - methods; Tissue Distribution; Tissues
• ISSN: 0013-936X; 1520-5851
• DOI: 10.1021/es101334s

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 106 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 105 M−1 for PFOA and PFNA and 104 M−1 for perfluorodecanoate and perfluorooctanesulfonate. The results reported here suggest binding through specific high affinity interactions at low PFAA:albumin mole ratios.