Determining the molecular interactions of perfluorinated carboxylic acids with human sera and isolated human serum albumin using nuclear magnetic resonance spectroscopy.
Environ Toxicol Chem
; 29(8): 1678-88, 2010 Aug.
Article
em En
| MEDLINE
| ID: mdl-20821619
ABSTRACT
Perfluorooctanoate (PFOA) is ubiquitous in North American human sera and has a serum half-life of 3.5 years in humans. The molecular interactions that lead to the bioaccumulation of these hydrophobic and lipophobic molecules in human blood are not well understood. Perfluorohexanoic acid (PFHxA) and PFOA were used as model perfluorinated carboxylic acids (PFCAs) to characterize the major site of PFCA interaction in human sera. Using novel heteronuclear saturation transfer difference nuclear magnetic resonance spectroscopy experiments, human serum albumin (HSA) was identified as the major site of interaction for both PFHxA and PFOA in human sera. Heteronuclear single quantum coherence nuclear magnetic resonance experiments were then performed to interrogate site-specific interactions of PFHxA and PFOA with isolated HSA. Perfluorohexanoic acid was found to bind specifically to Sudlow's drug-binding site II, whereas PFOA interacted preferentially with Sudlow's drug-binding site I at the lower concentration, with additional interactions developing at the higher concentration. These experiments highlight the utility of nuclear magnetic resonance spectrometry as a tool to observe the in situ interactions of chemical contaminants with biological systems. Both PFCAs displaced the endogenous HSA ligand oleic acid at concentrations lower than observed for the drugs ibuprofen and phenylbutazone, which are established HSA ligands. Interactions between PFCAs and HSA may affect the pharmacokinetics and distribution of fatty acids and certain drugs in the human body and warrant further investigation.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Albumina Sérica
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Ácidos Carboxílicos
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Poluentes Ambientais
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Fluorocarbonos
Limite:
Humans
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article