Binding of perfluorinated fatty acids to serum proteins

  title={Binding of perfluorinated fatty acids to serum proteins},
  author={Paul D. Jones and Wenyue Hu and Wim M. De Coen and John Newsted and John P. Giesy},
  journal={Environmental Toxicology and Chemistry},
Perfluorooctane sulfonic acid (PFOS) accumulates in the liver and blood of exposed organisms. The potential for these surfactant molecules to interfere with hormone/protein interactions in blood is of concern given the importance of these interactions. The PFOS binding to serum proteins was investigated by assessing its ability to displace a variety of steroid hormones from specific binding proteins in the serum of birds and fishes. Perfluorooctane sulfonic acid had only a weak ability to… 

Noncovalent interactions of long-chain perfluoroalkyl acids with serum albumin.

The results reported here suggest binding through specific high affinity interactions at low PFAA:albumin mole ratios.

Bioconcentration of perfluorinated alkyl acids: how important is specific binding?

This work presents the first mechanistic protein-binding bioconcentration model for PFAAs in fish that considers PFAA uptake via passive diffusion at the gills, association with serum albumin in the circulatory and extracellular spaces, and renal elimination and reabsorption facilitated by OAT proteins.

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

Fluorescence titrations support evidence that an observed dependence of PFAA‐BSA binding on pH is attributable to conformational changes in the protein, suggesting that physiological implications of strong binding to albumin may be important for short‐chain PFAAs.

Unveiling the binding mode of perfluorooctanoic acid to human serum albumin

The elucidation of the molecular basis of the interaction between PFOA and hSA might provide not only a better assessment of the absorption and elimination mechanisms of these compounds in vivo but also have implications for the development of novel molecular receptors for diagnostic and biotechnological applications.

Structure-based investigation on the interaction of perfluorinated compounds with human liver fatty acid binding protein.

The possibility of in vivo competitive displacement of fatty acids from FABP by PFCs was estimated and the binding constant obtained showed that PFC binding induced distinctive structural changes of the protein.

Binding of PFOS to serum albumin and DNA: insight into the molecular toxicity of perfluorochemicals

The ion bond, van der Waals force and hydrophobic interaction contributed to PFOS binding to peptide chain of SA and to the groove bases of DNA duplex, with the physiological function of SA to transport Vitamin B2 being inhibited consequently.

Competitive binding of poly- and perfluorinated compounds to the thyroid hormone transport protein transthyretin.

Competitive binding of PFCs to TTR, as observed for human TTR in the present study, may explain altered thyroid hormone levels described for PFC-exposed rats and monkeys.

Experimental characterization of the mechanism of perfluorocarboxylic acids' liver protein bioaccumulation: The key role of the neutral species

Routine pharmacochemical models may be applicable to predicting the protein‐based bioaccumulation of long‐chain PFCAs and a comparison of their chemical and physical properties with other well‐studied biologically relevant chemicals showed that accumulation of P FCAs in proteins as the neutral species is predictable.

Identification of perfluorooctane sulfonate binding protein in the plasma of tiger pufferfish Takifugu rubripes.




Interactions of fluorochemicals with rat liver fatty acid-binding protein.

In vitro data presented in this study support the hypothesis that these fluorochemicals may interfere with the binding of fatty acids or other endogenous ligands to L-FABP and provide evidence to support the hypotheses that displacement of endogenous ligand from L- FABP may contribute to toxicity in rodents fed these fluorochemistryicals.

Binding of the General Anesthetics Propofol and Halothane to Human Serum Albumin

It is shown that the intravenous anesthetic propofol binds at two discrete sites on HSA in preformed pockets that have been shown to accommodate fatty acids, and that the inhalational agent halothane binds at three sites that are also fatty acid binding loci.

Interactions between human plasma sex hormone-binding globulin and xenobiotic ligands

Transport of steroid hormones: interaction of 70 drugs with testosterone-binding globulin and corticosteroid-binding globulin in human plasma.

The results indicate that binding to steroid transport proteins should be considered among the in vivo effects of drugs on endogenous steroid hormone levels.

Accumulation of perfluorooctane sulfonate in marine mammals.

The occurrence of PFOS in marine mammals from the Arctic waters suggests widespread global distribution ofPFOS including remote locations.

Subchronic toxicity studies on perfluorooctanesulfonate potassium salt in cynomolgus monkeys.

Comparison of serum PFOS concentrations associated with no adverse effect in this study to those reported in human blood samples indicated an adequate margin of safety.

Characteristics of the binding of corticosteroid-binding globulin to rat cell membranes.

Specific binding sites for corticosteroid-binding globulin (CBG) were detected on membranes prepared from rat spleen, and electrophoretic patterns from uterine, pulmonary, and renal membranes showed that the less mobile band of the normal CBG doublet appeared to be metabolized to a greater extent than the more mobile band.

Crystallographic analysis reveals common modes of binding of medium and long-chain fatty acids to human serum albumin.

A crystallographic study of five HSA-fatty acid complexes formed using saturated medium-chain and long-chain fatty acids reveals key similarities and significant differences in the modes of binding, and serves to rationalise much of the biochemical data on fatty acid interactions with albumin.