Interaction of Aflatoxin B1with Cytochrome P450 2A5 and Its Mutants:  Correlation with Metabolic Activation and Toxicity

1997 ◽  
Vol 10 (1) ◽  
pp. 85-90 ◽  
Author(s):  
Päivi Pelkonen ◽  
Matti A. Lang ◽  
Masahiko Negishi ◽  
Christopher P. Wild ◽  
Risto O. Juvonen
Keyword(s):  
Cytochrome P450 ◽  
Metabolic Activation

Role of metabolic activation by cytochrome P450 in thioacetamide-induced suppression of antibody response in male BALB/c mice

2000 ◽  
Vol 114 (1-3) ◽  
pp. 225-235 ◽  
Author(s):  
Kap-Ho Kim ◽  
Ju-Hyun Bae ◽  
Shin-Woo Cha ◽  
Sang-Seop Han ◽  
Kwan Ha Park ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Antibody Response ◽  
Metabolic Activation

scholarly journals Cytochrome P450/NADPH-dependent biosynthesis of 5,6-trans-epoxyeicosatrienoic acid from 5,6-trans-arachidonic acid

2005 ◽  
Vol 390 (3) ◽  
pp. 719-727 ◽  
Author(s):  
Uzzal Roy ◽  
Robert Joshua ◽  
Russell L. Stark ◽  
Michael Balazy
Keyword(s):  
Arachidonic Acid ◽  
Cytochrome P450 ◽  
Fatty Acid ◽  
Trans Fatty Acid ◽  
Oxidative Metabolism ◽  
Liver Microsomes ◽  
Complex Mixture ◽  
Metabolic Activation ◽  
Lipid Mediator ◽  
Epoxyeicosatrienoic Acid

5,6-trans-AA (5,6-TAA, where TAA stands for trans-arachidonic acid) is a recently identified trans fatty acid that originates from the cis–trans isomerization of AA initiated by the NO2 radical. This trans fatty acid has been detected in blood circulation and we suggested that it functions as a lipid mediator of the toxic effects of NO2. To understand its role as a lipid mediator, we studied the metabolism of 5,6-TAA by liver microsomes stimulated with NADPH. Profiling of metabolites by liquid chromatography/MS revealed a complex mixture of oxidized products among which were four epoxides, their respective hydrolysis products (dihydroxyeicosatrienoic acids), and several HETEs (hydroxyeicosatetraenoic acids) resulting from allylic, bis-allylic and (ω−1)/(ω−2) hydroxylations. We found that the C5–C6 trans bond competed with the three cis bonds for oxidative metabolism mediated by CYP (cytochrome P450) epoxygenase and hydroxylase. This was evidenced by the detection of 5,6-trans-EET (where EET stands for epoxyeicosatrienoic acid), 5,6-erythro-dihydroxyeicosatrienoic acid and an isomer of 5-HETE. A standard of 5,6-trans-EET obtained by iodolactonization of 5,6-TAA was used for the unequivocal identification of the unique microsomal epoxide in which the oxirane ring was of trans configuration. Additional lipid products originated from the metabolism involving the cis bonds and thus these metabolites had the trans C5–C6 bond. The 5,6-trans-isomers of 18- and 19-HETE were likely to be products of the CYP2E1, because a neutralizing antibody partially inhibited their formation without having an effect on the formation of the epoxides. Our study revealed a novel pathway of microsomal oxidative metabolism of a trans fatty acid in which both cis and trans bonds participated. Of particular significance is the detection of the trans-epoxide of AA, which may be involved in the metabolic activation of such trans fatty acids and probably contribute to their biological activity. Unlike its cis-isomer, 5,6-trans-EET was significantly more stable and resisted microsomal hydrolysis and conjugation with glutathione catalysed by hepatic glutathione S-transferase.

scholarly journals Metabolic Activation of Proestrogens in the Environment by Cytochrome P450 System

2008 ◽  
Vol 54 (4) ◽  
pp. 343-355 ◽  
Author(s):  
Shigeyuki Kitamura ◽  
Kazumi Sugihara ◽  
Seigo Sanoh ◽  
Nariaki Fujimoto ◽  
Shigeru Ohta
Keyword(s):  
Cytochrome P450 ◽  
Metabolic Activation ◽  
Cytochrome P450 System

Metabolic Activation of Benzo[c]phenanthrene by Cytochrome P450 Enzymes in Human Liver and Lung

2001 ◽  
Vol 14 (6) ◽  
pp. 686-693 ◽  
Author(s):  
Matthias Baum ◽  
Shantu Amin ◽  
F. Peter Guengerich ◽  
Stephen S. Hecht ◽  
Werner Köhl ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Human Liver ◽  
Metabolic Activation ◽  
Cytochrome P450 Enzymes
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