Analysis of medaka cytochrome P450 3A homotropic and heterotropic cooperativity

We have previously demonstrated that medaka CYP3A is associated with metabolism of several endobiotics including steroids and bile acids. In this study, we demonstrate that medaka CYP3A catalysis exhibits unusual kinetic behaviors consistent with allosteric interaction which cannot be described by h...

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Bibliographic Details
Published in:Marine environmental research 2004-08, Vol.58 (2), p.469-473
Main Authors: Kullman, Seth W., Kashiwada, Shosaku, Hinton, David E.
Format: Article
Language:English
Subjects:
Animal and plant ecology
Animal, plant and microbial ecology
Animals
Aryl Hydrocarbon Hydroxylases - metabolism
Biological and medical sciences
Catalysis
Coumarins - metabolism
Cytochrome P-450 CYP3A
Fluorescence
Fundamental and applied biological sciences. Psychology
Kinetics
Models, Chemical
Oryzias - metabolism
Oryzias latipes
Oxidoreductases, N-Demethylating - metabolism
Phenols - metabolism
Protein Binding
Sea water ecosystems
Substrate Specificity
Synecology
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Summary:We have previously demonstrated that medaka CYP3A is associated with metabolism of several endobiotics including steroids and bile acids. In this study, we demonstrate that medaka CYP3A catalysis exhibits unusual kinetic behaviors consistent with allosteric interaction which cannot be described by hyperbolic kinetic models. Using 7-benzyloxy-4-(trifluoromethyl)-coumarin (BFC) and nonylphenol as CYP3A substrates, we describe both homotropic and heterotropic cooperative interactions. Given the role of CYP3A in maintaining the homeostatic balance for numerous endobiotics, enzymatic activation/inhibition by endocrine disruptors (EDCs) represents a putative (non-genomic) mechanism for endocrine disruption.
ISSN:0141-1136
1879-0291
DOI:10.1016/j.marenvres.2004.03.030