Binding of Polychlorinated Biphenyls to the Aryl Hydrocarbon Receptor

A new thermodynamic model for calculating the dissociation constants of complexes formed between the aryl hydrocarbon receptor (AhR) and polychlorinated biphenyls (PCBs) is reported. The free energies of binding of PCBs to AhR are controlled by their lipophilicities, electron affinities, and entropi...

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Bibliographic Details
Published in:Environmental health perspectives 1993-10, Vol.101 (5), p.422-428
Main Authors: Kafafi, Sherif A., Afeefy, Hussein Y., Ali H. Ali, Said, Hakim K., Kafafi, Abdel G.
Format: Article
Language:English
Subjects:
550200 - Biochemistry
550500 - Metabolism
Animals
AROMATICS
ARYL 4-MONOOXYGENASE
Atoms
BASIC BIOLOGICAL SCIENCES
BIOCHEMICAL REACTION KINETICS
CHLORINATED AROMATIC HYDROCARBONS
Congeners
Electron affinity
Entropy
Environmental health
ENZYMES
HALOGENATED AROMATIC HYDROCARBONS
KINETICS
Ligands
Lipids - chemistry
MATHEMATICAL MODELS
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
OXIDOREDUCTASES
PARTICLE MODELS
POLYCHLORINATED BIPHENYLS
Polychlorinated Biphenyls - metabolism
PROTEINS
REACTION KINETICS
Receptors
Receptors, Aryl Hydrocarbon - metabolism
Solubility
STATISTICAL MODELS
Structure-Activity Relationship
STRUCTURE-ACTIVITY RELATIONSHIPS
THERMODYNAMIC MODEL
Thermodynamics
TOXICITY
XENOBIOTICS
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Summary:A new thermodynamic model for calculating the dissociation constants of complexes formed between the aryl hydrocarbon receptor (AhR) and polychlorinated biphenyls (PCBs) is reported. The free energies of binding of PCBs to AhR are controlled by their lipophilicities, electron affinities, and entropies. The corresponding physicochemical properties of polychlorinated dibenzo-p-dioxins and dibenzofurans also control their interactions with AhR. We present evidence supporting the hypothesis that the majority of PCBs are likely to interact with AhR in their nonplanar conformations. In addition, we demonstrate that the affinities of PCBs for AhR relative to 2,3,7,8-tetrachlorodibenzo-p-dioxin correlate with corresponding toxic equivalency factors in animals. The reported methodology is likely to be applicable to other polyhalogenated and mixed polyhalogenated bi- and terphenyls and related xenobiotics; thus, it could minimize the number of in vivo studies in laboratory animals and facilitate the identification of potentially hazardous aromatic xenobiotics.
ISSN:0091-6765
1552-9924
DOI:10.1289/ehp.93101422