US EPA

3859962 

Journal Article 

Depletion of mitochondrial CoA by perfluorosulfonic and perfluorocarboxylic acids in vitro 

O'Brien, TM; Wallace, KB 

2004 

1 

Toxicologist
ISSN: 0731-9193 

78 

1 Suppl. 

104 

English 

Perfluorooctanesulfonate (PFOS), perfluorooctanoic acid (PFOA), and the substituted perfluorooctanesulfonamides perfluorooctanesulfonamidoacetate (FOSAA), and N-ethylperfluorooctanesulfonamidoacetate (N-Et-FOSAA) are widely used as surfactants on fabrics and papers, as anti-corrosion agents and fire retardants, as well as many other commercial applications. Their broad use, global distribution, and environmental persistence has generated considerable interest regarding the metabolic and potentially toxic effects of these compounds. We have previously shown that the perfluorooctanes disrupt mitochondrial bioenergetics and, more specifically, that perfluorinated carboxylic acids induce the mitochondrial permeability transition. The purpose of this study was to determine if, as structural fatty acid analogues, perfluorosulfonic acid and perfluorinated carboxylic acids deplete free coenzyme A. Freshly homogenized rat liver was incubated in the presence of the test compound at 37 C for 40 minutes. Caprylic acid was included as a positive control and the concentration of free coenzyme A determined by reversed-phase HPLC. The concentration of free CoA detected in the control incubations was 92.4 +/- 13.6 nmol/g liver. Incubation with caprylic acid caused a 5% decrease in free CoA, whereas there was a 15%-40% depletion of CoA when liver tissue was incubated with one or another of the perfluorinated acids. We conclude that PFOS and the perfluorinated carboxylic acids deplete free mitochondrial coenzyme A, and that this may contribute to the mechanism by which these compounds interfere with fatty acid metabolism in vivo