Covalent binding of perfluorinated fatty acids to proteins in the plasma, liver and testes of rats

John P. Vanden Heuvel, Benedict I. Kuslikis, Richard E. Peterson

Research output: Contribution to journalArticlepeer-review

64 Scopus citations

Abstract

Perfluorinated fatty acids alter hepatic lipid metabolism and are potent peroxisome proliferators in rodents. Two such perfluorinated acids, perfluorodecanoic acid (PFDA) and perfluorooctanoic acid (PFOA), were examined to determine if they covalently bind cellular proteins. PFDA and PFOA were found to covalently bind proteins when administered to rats in vivo. The liver, plasma and testes of male rats treated with [1-14C]PFDA or PFOA (9.4 μmol/kg) contained detectable levels of covalently bound 14C (0.1-0.5% of the tissue 14C content). Characterization of PFDA covalent binding to albumin in vitro showed that cysteine significantly decreased binding with no effect of methionine, suggesting protein sulfhydryl groups are involved. In cytosolic and microsomal incubation there was no effect of the addition of CoA, ATP or NADPH on the magnitude of the covalent binding of PFDA. Therefore PFDA need not be metabolically activated to form covalent adducts. Despite demonstration of covalent binding of PFDA and PFOA to proteins both in vivo and in vitro, the role of this macromolecular binding in perfluorinated fatty acid toxicity is not known.

Original languageEnglish (US)
Pages (from-to)317-328
Number of pages12
JournalChemico-Biological Interactions
Volume82
Issue number3
DOIs
StatePublished - May 1992

All Science Journal Classification (ASJC) codes

  • Toxicology

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