Strong associations of short‐chain perfluoroalkyl acids with serum albumin and investigation of binding mechanisms

Abstract

Interactions of perfluoroalkyl acids (PFAAs) with tissue and serum proteins likely contribute to their tissue distribution and bioaccumulation patterns. Protein-water distribution coefficients (K(PW) ) based on ligand associations with bovine serum albumin (BSA) as a model protein were recently proposed as biologically relevant parameters to describe the environmental behavior of PFAAs, yet empirical data on such protein binding behavior are limited. In the present study, associations of perfluoroalkyl carboxylates (PFCAs) with two to 12 carbons (C₂-C₁₂) and perfluoroalkyl sulfonates with four to eight carbons (C₄, C₆, and C₈) with BSA are evaluated at low PFAA:albumin mole ratios and various solution conditions using equilibrium dialysis, nanoelectrospray ionization mass spectrometry, and fluorescence spectroscopy. Log K(PW) values for C₄ to C₁₂ PFAAs range from 3.3 to 4.3. Affinity for BSA increases with PFAA hydrophobicity but decreases from the C₈ to C₁₂ PFCAs, likely due to steric hindrances associated with longer and more rigid perfluoroalkyl chains. The C₄-sulfonate exhibits increased affinity relative to the equivalent chain-length PFCA. Fluorescence titrations support evidence that an observed dependence of PFAA-BSA binding on pH is attributable to conformational changes in the protein. Association constants determined for perfluorobutanesulfonate and perfluoropentanoate with BSA are on the order of those for long-chain PFAAs (K(a) ∼10⁶/M), suggesting that physiological implications of strong binding to albumin may be important for short-chain PFAAs.

Distribution of perfluoroalkyl compounds in rats: Indication for using hair as bioindicator of exposure

“…[37][38][39] Keratin protein is the main component of hair. The occurrences of PFOA, PFNA, and PFOS in hair, and the similar profile to that in the main tissues, suggested that the affinity of PFAAs to keratin possibly play a dominant role in the hair PFAA accumulation.…”

Highly Elevated Serum Concentrations of Perfluoroalkyl Substances in Fishery Employees from Tangxun Lake, China

“…Differences in renal clearance of PFCAs with differing chain lengths have primarily been attributed to their binding affinities to serum albumin and different sets of organic anion transporter proteins that govern the reabsorption of PFCAs from urine to blood. 55−57 A recent study that investigated bovine serum albumin-water distribution coefficients (K PW ) demonstrated a positive association between binding affinities and the perfluoroalkyl chain, 56 and the few data so far on human elimination of short-chain PFCAs indicate a substantially faster clearance of PFBA compared to PFHxA. 17,18 Interestingly, our data displayed similar or slightly lower clearance rates for PFBA compared to PFHxA and PFHpA (Figure 3), although no significant differences were observed for clearance rates among these three PFCAs according to the statistical test.…”

The roles of protein and lipid in the accumulation and distribution of perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) in plants grown in biosolids-amended soils

“…The distribution of PFASs in proteinrich tissues, rather than in fat tissues, and the high affinity to some proteins highlighted the proteinophilic nature of PFASs Bischel et al, 2011Bischel et al, , 2010. Though the serum proteins do not exist in plants, fatty acid binding proteins have been found in plants (Arondel et al, 1990;Rickers et al, 1984).…”