Effects of bioavailability in an in vitro metabolism assay

Kwon, J. H., Rutishauser, S. and Escher, B. I. (2009). Effects of bioavailability in an in vitro metabolism assay. In: SETAC Europe 19th Annual Meeting Protecting ecosystem health: facing the challenge of a globally changing environment. SETAC Europe 19th Annual Meeting Protecting ecosystem health: facing the challenge of a globally changing environment, Convention Centre in Göteborg, Sweden, (). 31 May until 4 June 2009.

Author Kwon, J. H.
Rutishauser, S.
Escher, B. I.
Title of paper Effects of bioavailability in an in vitro metabolism assay
Formatted title
Effects of bioavailability in an in vitro metabolism assay
Conference name SETAC Europe 19th Annual Meeting Protecting ecosystem health: facing the challenge of a globally changing environment
Conference location Convention Centre in Göteborg, Sweden
Conference dates 31 May until 4 June 2009
Convener SETAC Europe
Proceedings title SETAC Europe 19th Annual Meeting Protecting ecosystem health: facing the challenge of a globally changing environment
Publication Year 2009
Year available 2009
Sub-type Fully published paper
Language eng
Abstract/Summary Enzymatic degradation of highly hydrophobic compounds is of significant interest because their persistence and bioaccumulation potential strongly depend on their metabolic degradation rate. It is well-known that hydrophobic chemicals strongly bind onto cellular matrices and this binding affect their bioavailability. However, it has been rarely investigated how cellular bindings affects their degradation kinetics in in vitro metabolism assays. Thus, we evaluated the effects of non-specific bindings on the apparent enzymatic kinetics in an in vitro assay using two highly hydrophobic compounds, pyrene and benzo[a]pyrene, as model hydrophobic compounds and S9 mixture isolated from rat liver as a model enzyme mixture. In addition, bovine serum albumin (BSA) was selected as non-metabolically active protein in order to investigate effects of binding onto proteins. Apparent enzymatic kinetics at various experimental conditions could neither be explained by the classical Michaelis-Menten model nor by a non-specific binding model assuming that non-specifically bound compounds are not available for enzymatic degradation. Thus, a new model was developed to explain the experimental data. This model includes kinetic exchanges between non-specifically bound form and solute bound to metabolically active sites. The experimental data were well-explained by the new model. Input parameters to the model were experimentally determined partition coefficients between S9 or BSA and buffer solution. This model was also supported by a series of degradation experiments in presence of various concentrations of BSA
Subjects 111506 Toxicology (incl.Clinical Toxicology)
EX
920405 Environmental Health
Q-Index Code EX
Q-Index Status Provisional Code

Document type: Conference Paper
Collection: National Research Centre for Environmental Toxicology Publications
 
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Created: Mon, 15 Mar 2010, 21:11:53 EST by Professor Beate Escher on behalf of National Res Centre For Environmental Toxicology