Isomer-Specific
Binding Affinity of Perfluorooctanesulfonate
(PFOS) and Perfluorooctanoate (PFOA) to Serum Proteins
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Abstract
Perfluorooctanesulfonate (PFOS) and
perfluorooctanoate (PFOA) are
among the most prominent contaminants in human serum, and these were
historically manufactured as technical mixtures of linear and branched
isomers. The isomers display unique pharmacokinetics in humans and
in animal models, but molecular mechanisms underlying isomer-specific
PFOS and PFOA disposition have not previously been studied. Here,
ultrafiltration devices were used to examine (i) the dissociation
constants (<i>K</i><sub>d</sub>) of individual PFOS and
PFOA isomers with human serum albumin (HSA) and (ii) relative binding
affinity of isomers in technical mixtures spiked to whole calf serum
and human serum. Measurement of HSA <i>K</i><sub>d</sub>’s demonstrated that linear PFOS (<i>K</i><sub>d</sub> = 8(±4) × 10<sup>–8</sup> M) was much more tightly
bound than branched PFOS isomers (<i>K</i><sub>d</sub> range
from 8(±1) × 10<sup>–5</sup> M to 4(±2) ×
10<sup>–4</sup> M). Similarly, linear PFOA (<i>K</i><sub>d</sub> = 1(±0.9) × 10<sup>–4</sup> M) was
more strongly bound to HSA compared to branched PFOA isomers (<i>K</i><sub>d</sub> range from 4(±2) × 10<sup>–4</sup> M to 3(±2) × 10<sup>–4</sup> M). The higher binding
affinities of linear PFOS and PFOA to total serum protein were confirmed
when both calf serum and human serum were spiked with technical mixtures.
Overall, these data provide a mechanistic explanation for the longer
biological half-life of PFOS in humans, compared to PFOA, and for
the higher transplacental transfer efficiencies and renal clearance
of branched PFOS and PFOA isomers, compared to the respective linear
isomer