Utility of Intersystem Extrapolation Factors in Early Reaction Phenotyping and the Quantitative Extrapolation of Human Liver Microsomal Intrinsic Clearance Using Recombinant Cytochromes P450

2010 ◽  
Vol 39 (3) ◽  
pp. 373-382 ◽  
Author(s):  
Yuan Chen ◽  
Liling Liu ◽  
Khanh Nguyen ◽  
Adrian J. Fretland
Keyword(s):  
Human Liver ◽  
Cytochromes P450 ◽  
Intrinsic Clearance ◽  
Early Reaction ◽  
Reaction Phenotyping

Interaction of isoflavonoids with human liver microsomal cytochromes P450: inhibition of CYP enzyme activities

Xenobiotica ◽  
2016 ◽  
Vol 47 (4) ◽  
pp. 324-331 ◽  
Author(s):  
Michaela Kopečná-Zapletalová ◽  
Kristýna Krasulová ◽  
Pavel Anzenbacher ◽  
Petr Hodek ◽  
Eva Anzenbacherová
Keyword(s):  
Enzyme Activities ◽  
Human Liver ◽  
Cytochromes P450

scholarly journals Multiple-Approaches to the Identification and Quantification of Cytochromes P450 in Human Liver Tissue by Mass Spectrometry

2009 ◽  
Vol 8 (4) ◽  
pp. 1672-1681 ◽  
Author(s):  
Cathrin Seibert ◽  
Brian R. Davidson ◽  
Barry J. Fuller ◽  
Laurence H. Patterson ◽  
William J. Griffiths ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Liver Tissue ◽  
Human Liver ◽  
Cytochromes P450 ◽  
Human Liver Tissue ◽  
Identification And Quantification

scholarly journals INTERACTION OF AROMATIC CYTOKININS WITH HUMAN LIVER MICROSOMAL CYTOCHROMES P450

2005 ◽  
Vol 149 (2) ◽  
pp. 349-351 ◽  
Author(s):  
Eva Anzenbacherova ◽  
Jakub Janalik ◽  
Igor Popa ◽  
Miroslav Strnad ◽  
Pavel Anzenbacher
Keyword(s):  
Human Liver ◽  
Cytochromes P450 ◽  
Aromatic Cytokinins

Characterization of human liver cytochromes P450 by combining the biochemical and proteomic approaches

2006 ◽  
Vol 20 (6) ◽  
pp. 966-974 ◽  
Author(s):  
N.A. Petushkova ◽  
I.P. Kanaeva ◽  
A.V. Lisitsa ◽  
G.F. Sheremetyeva ◽  
V.G. Zgoda ◽  
...  
Keyword(s):  
Human Liver ◽  
Cytochromes P450

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.

scholarly journals CYP-Dependent Metabolism of PF9601N, A New Monoamine Oxidase-B Inhibitor, by C57BL / 6 Mouse and Human Liver Microsomes

2007 ◽  
Vol 10 (4) ◽  
pp. 473 ◽  
Author(s):  
Stefania Dragoni ◽  
Giada Materozzi ◽  
Federica Pessina ◽  
Maria Frosini ◽  
José Luis Marco ◽  
...  
Keyword(s):  
Monoamine Oxidase ◽  
Human Liver ◽  
Formation Rate ◽  
Antioxidant Properties ◽  
Liver Microsomes ◽  
Intrinsic Clearance ◽  
Human Liver Microsomes ◽  
Monoamine Oxidase B ◽  
Mao B

Purpose. The selective monoamine oxidase-B (MAO-B) inhibitor, l-deprenyl, is still used for treating Parkinson's patients, however, a disadvantage of its use lies in the formation of l-amphetamine and l-methamphetamine. Subsequently, this has promoted the design of a novel, more potent, MAO-B inhibitor PF9601N, which also has neuroprotective and antioxidant properties. The aim of this work was to investigate the effect of treatment with PF9601N on its own phase I hepatic metabolism. Kinetic parameters of PF9601N CYP-dependent N-dealkylation reaction was also studied and compared with those of l-deprenyl. Methods. C57BL/6 mice were treated with PF9601N for 4 days. After CYP content and related monooxygenase activities were assayed in liver microsomes of control and treated animals. Results. CYP activities, cytochrome b5 content, NADPH-cytochrome P450 reductase and various monooxygenase activities were unaffected by in vivo PF9601N treatment. With microsomes from both control and treated mice, the PF9601N-dealkylation product, FA72, was the only detected metabolite with its formation rate following an hyperbolic, Michaelis-Menten curve. Among various inhibitors, only ketoconazole inhibited the FA72 formation rate, indicating a major involvement for CYP3A. Apparent Km and Vmax values generated by human liver microsomes were similar to those found with mouse microsomes. Ketoconazole inhibition indicates that CYP3A is one of the major enzymes involved in PF9601N metabolism also by human liver microsomes. In mouse liver microsomes, the intrinsic clearance of PF9601N was significantly lower than that of l-deprenyl suggestive of an improved bioavailability for the former. Conclusion. The observed favourable metabolic profile may suggest suitability of PF9601N for clinical use.

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