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Differential mechanisms for the inhibition of human cytochrome P450 1A2 by apigenin and genistein

✍ Scribed by Hideaki Shimada; Masashi Eto; Misa Ohtaguro; Michihiro Ohtsubo; Yosuke Mizukami; Tsuyoshi Ide; Yorishige Imamura

Publisher
John Wiley and Sons
Year
2010
Tongue
English
Weight
240 KB
Volume
24
Category
Article
ISSN
1095-6670

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✦ Synopsis

Abstract

The inhibitory effects of flavonoids on the human cytochrome P450 1A2 (CYP1A2) were examined. Among flavonoids tested, galangin, kaempferol, chrysin, and apigenin were potent inhibitors. Although apigenin belonging to flavones and genistein belonging to isoflavones are similar in the chemical structures, the inhibitory potencies for CYP1A2 were distinguished markedly between these two flavonoids. In computer‐docking simulation, apigenin interacted with the same mode of cocrystallized α‐naphthoflavone in the active site of CYP1A2, and then the B ring of apigenin was placed close to the heme iron of the enzyme with a single orientation. In contrast, the docked genistein conformation showed two different binding modes, and the A ring of genistein was oriented to the heme iron of CYP1A2. Furthermore, the binding free energy of apigenin was lower than that of genistein. These results demonstrate a possible mechanism that causes the differential inhibitory potencies of apigenin and genistein for CYP1A2. © 2010 Wiley Periodicals, Inc. J Biochem Mol Toxicol 24:230–234, 2010; View this article online at wileyonlinelibrary.com. DOI 10.1002/jbt.20328

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