| Experimental characterization of the mechanism of perfluorocarboxylic acids' liver protein bioaccumulation: the key role of the neutral species. | |
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MedLine Citation:
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PMID: 20821618 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Perfluorocarboxylic acids (PFCAs) of chain length greater than seven carbon atoms bioconcentrate in the livers of fish. However, a mechanistic cause for the empirically observed increase in the bioconcentration potential of PFCAs as a function of chain length has yet to be determined. To this end, recombinant rat liver fatty acid-binding protein (L-FABP) was purified, and its interaction with PFCAs was characterized in an aqueous system at pH 7.4. Relative binding affinities of L-FABP with PFCAs of carbon chain lengths of five to nine were established fluorimetrically. The energetics, mechanism, and stoichiometry of the interaction of perfluorooctanoic acid (PFOA) with L-FABP were examined further by isothermal titration calorimetry (ITC) and electrospray ionization combined with tandem mass spectrometry (ESI-MS/MS). Perfluorooctanoic acid was shown to bind to L-FABP with an affinity approximately an order of magnitude less than the natural ligand, oleic acid, and to have at least 3:1 PFOA:L-FABP stoichiometry. Two distinct modes of PFOA binding to L-FABP were observed by ESI-MS/MS analysis; in both cases, PFOA binds solely as the neutral species under typical physiological pH and aqueous concentrations of the anion. A comparison of their chemical and physical properties with other well-studied biologically relevant chemicals showed that accumulation of PFCAs in proteins as the neutral species is predictable. For example, the interaction of PFOA with L-FABP is almost identical to that of the acidic ionizing drugs ketolac, ibuprofen, and warfarin that show specificity to protein partitioning with a magnitude that is proportional to the K(OW) (octanol-water partitioning) of the neutral species. The experimental results suggest that routine pharmacochemical models may be applicable to predicting the protein-based bioaccumulation of long-chain PFCAs. |
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Authors:
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Mark W Woodcroft; David A Ellis; Steven P Rafferty; Darcy C Burns; Raymond E March; Naomi L Stock; Kyle S Trumpour; Janet Yee; Kim Munro |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Environmental toxicology and chemistry / SETAC Volume: 29 ISSN: 1552-8618 ISO Abbreviation: Environ. Toxicol. Chem. Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-09-07 Completed Date: 2010-12-28 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8308958 Medline TA: Environ Toxicol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 1669-77 Citation Subset: IM |
Copyright Information:
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Copyright 2010 SETAC |
Affiliation:
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Department of Chemistry, Trent University, 1600 West Bank Drive, Peterborough, Ontario K9J 7B8, Canada. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Carboxylic Acids Fatty Acid-Binding Proteins / chemistry, metabolism Fishes / metabolism Fluorocarbons / chemistry, metabolism* Liver / chemistry, metabolism* Octanoic Acids / chemistry, metabolism Water Pollutants, Chemical / chemistry, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Carboxylic Acids; 0/Fatty Acid-Binding Proteins; 0/Fluorocarbons; 0/Octanoic Acids; 0/Water Pollutants, Chemical; 335-67-1/perfluorooctanoic acid |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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