AN ANALYSIS OF THE REGIOSELECTIVITY OF AROMATIC HYDROXYLATION AND N-OXYGENATION BY CYTOCHROME P450 ENZYMES

2004 ◽  
Vol 32 (3) ◽  
pp. 328-332 ◽  
Author(s):  
Tamara S. Dowers ◽  
Dan A. Rock ◽  
Denise A. Rock ◽  
Brandon N. S. Perkins ◽  
Jeffery P. Jones
Keyword(s):  
Cytochrome P450 ◽  
Cytochrome P450 Enzymes ◽  
Aromatic Hydroxylation

scholarly journals Characterization of O-demethylations and Aromatic Hydroxylations Mediated by Cytochromes P450 in the Metabolism of Flavonoid Aglycons

2019 ◽  
Vol 92 (1) ◽  
pp. 115-123 ◽  
Author(s):  
Goran Benković ◽  
Hrvoje Rimac ◽  
Željan Maleš ◽  
Siniša Tomić ◽  
Zoran Lončar ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Human Liver ◽  
Cytochromes P450 ◽  
Liver Microsomes ◽  
Cytochrome P450 Enzymes ◽  
Uv Detector ◽  
Aromatic Hydroxylation ◽  
Metabolism Of Xenobiotics ◽  
Kinetics Of

One of the most important groups of metabolic enzymes is cytochrome P450 superfamily. These enzymes are important in terms of the catalytic diversity and the large number of xenobiotics that are detoxified or activated by converting to reactive metabolites. Flavonoids are xenobiotics to which humans are exposed through diet. Data on their oxidative metabolism mediated by cytochromes P450 are limited. The aim of this study was to determine the enzymatic kinetics of O-demethylation and aromatic hydroxylation of flavonoid aglycons on recombinant cytochrome P450 enzymes and human liver microsomes systems. The study was performed on ten flavonoids, namely 3,7-dihydroxyflavone, 7-hydroxyflavone, acacetin, apigenin, flavone, galangin, kaempferol, naringenin, sakuranetin, and tangeretin using liquid chromatography coupled with mass spectrometry and UV detector. Most relevant enzyme involved in metabolism of flavonoid aglycons is CYP1A2, and its catalytic effectiveness ranges from 0.5 to 2.9 × 106 M–1 min–1. Having in mind high expression and involvement of CYP1A2 in metabolism of xenobiotics including drugs, and its intraindividual differences in expression and activity, potential of drug-flavonoid competitive interactions/inhibitions should be considered when consuming dietary supplement and foods rich in flavonoids.

Pharmacogenomics of Cytochrome P450 Enzymes in Tumours

2004 ◽  
Vol 2 (3) ◽  
pp. 243-254 ◽  
Author(s):  
Diane Downie ◽  
Patrick Rooney ◽  
Morag McFadyen ◽  
Graeme Murray
Keyword(s):  
Cytochrome P450 ◽  
Cytochrome P450 Enzymes

Engineering Cytochrome P450 Enzymes

2008 ◽  
Vol 21 (1) ◽  
pp. 220-231 ◽  
Author(s):  
Elizabeth M. J. Gillam
Keyword(s):  
Cytochrome P450 ◽  
Cytochrome P450 Enzymes

scholarly journals Exploring the effect of khat (Catha edulis) chewing on the pharmacokinetics of the antiplatelet drug clopidogrel in rats using the newly developed LC-MS/MS technique

2020 ◽  
Vol 18 (1) ◽  
pp. 681-690
Author(s):  
Hassan A. Alhazmi ◽  
Adnan A. Kadi ◽  
Mohamed W. Attwa ◽  
Waquar Ahsan ◽  
Manal Mohamed Elhassan Taha ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Active Metabolite ◽  
Dose Adjustment ◽  
Internal Standard ◽  
Cardiovascular Complications ◽  
Antiplatelet Drug ◽  
Peak Ratio ◽  
Cytochrome P450 Enzymes ◽  
Time Intervals ◽  
Addictive Substance

AbstractClopidogrel (CLOP) is widely used worldwide for cardiovascular complications. CLOP is highly metabolized in the liver to its active metabolite by cytochrome P450 enzymes. Studies have shown that khat, an addictive substance, is a powerful inhibitor of cytochrome P450 enzymes and can influence the metabolism of drugs that are concomitantly used. Therefore, this study was designed to evaluate the effects of khat on the pharmacokinetics of CLOP in rats. In this study, rats were administered either CLOP alone or CLOP combined with khat and their plasma were obtained at different time intervals and analyzed using the newly developed and validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) method using foretinib (FTB) as the internal standard. The corresponding peak area of the analyte versus FTB was used for calculating the peak ratio. The validated LC-MS/MS method resulted in the separation of the well-defined quantifiable peaks of CLOP, FTB, and CLOP metabolite within 7 min. Results showed a significant influence of khat on the peak ratio of CLOP metabolite, which was found to be significantly decreased (P < 0.05) in comparison to CLOP alone, suggesting significant decrease in the conversion of CLOP to its active metabolite due to the inhibition of CYP450 enzymes by khat. Therefore, there might be a need for dose adjustment for regular khat chewers using CLOP.

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