Izvorni znanstveni članak
Characterization of O-demethylations and Aromatic Hydroxylations Mediated by Cytochromes P450 in the Metabolism of Flavonoid Aglycons
; Agency for Medicinal Products and Medical Devices, Ksaverska cesta 4, HR-10000 Zagreb, Croatia
Hrvoje Rimac orcid.org/0000-0001-7232-6489 ; University of Zagreb Faculty of Pharmacy and Biochemistry, Department of Pharmaceutical Chemistry, A. Kovačića 1, HR-10000 Zagreb, Croatia
Željan Maleš ; University of Zagreb Faculty of Pharmacy and Biochemistry, Department of Pharmaceutical Botany, Schrottova 39, HR-10000 Zagreb, Croatia
Siniša Tomić orcid.org/0000-0002-3500-9940 ; Agency for Medicinal Products and Medical Devices, Ksaverska cesta 4, HR-10000 Zagreb, Croatia
Zoran Lončar ; Clinic of Traumatology, Clinical Hospital Center Sisters of Charity, Draškovićeva 19, HR-10000 Zagreb, Croatia
Mirza Bojić orcid.org/0000-0002-8381-9577 ; University of Zagreb Faculty of Pharmacy and Biochemistry, Department of Pharmaceutical Chemistry, A. Kovačića 1, HR-10000 Zagreb, Croatia
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.
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