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• W2030201224 endingPage "397" @default.
• W2030201224 startingPage "384" @default.
• W2030201224 abstract "Saturation binding studies of the interaction between 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and the Ah receptor obtained from the hepatic cytosol of Wistar rats have been carried out. The conventional Scatchard analysis for determination of the equilibrium constant for ligand-receptor binding has been shown to be inappropriate due to thermal inactivation of the unoccupied receptor. Simulation models of the receptor-ligand binding kinetics which take into account receptor degradation have been developed and the results are consistent with two alternative kinetic models. In Model 1, reversible 2,3,7,8-TCDD-receptor binding occurs in parallel with inactivation of the unbound receptor; analysis of the observed data using this model suggests that the previously determined equilibrium constants (Kass) for association of the ligand with the receptor are orders of magnitude too low and the total initial receptor concentrations are somewhat underestimated. In Model 2, the unbound receptor is converted unimolecularly to an activated state which then undergoes competitive degradation or entrapment by ligand. Experiments have been carried out over the temperature range 4–37 °C, enabling activation parameters to be obtained. According to Scheme 1, the activation enthalpies for association of receptor with ligand and for thermal inactivation of the unoccupied receptor are high, and numerically almost identical (ΔH‡ ca 125 kJ mol−1). These reactions are strongly entropically driven and this is consistent with association being accompanied by a conformational change in the receptor protein, and the previously postulated binding of the ligand to a hydrophobic pocket. According to Scheme 2, there is only one enthalpy of activation because both inactivation and entrapment by 2,3,7,8-TCDD are fast processes which follow the same slow activation step. On the basis of this latter model, a 10−9m concentration of 2,3,7,8-TCDD is sufficient to trap roughly two-thirds of the activated receptors." @default.
• W2030201224 created "2016-06-24" @default.
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• W2030201224 date "1988-11-01" @default.
• W2030201224 modified "2023-10-10" @default.
• W2030201224 title "Kinetic models for association of 2,3,7,8-tetrachlorodibenzo-p-dioxin with the Ah receptor" @default.
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• W2030201224 doi "https://doi.org/10.1016/0003-9861(88)90044-6" @default.
• W2030201224 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/2848454" @default.
• W2030201224 hasPublicationYear "1988" @default.
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