Abstract
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.
Highlights
M ETABOLISM is one of the ways by which human organisms protect themselves from foreign substances i.e. xenobiotics
Enzyme kinetics was determined for 10 flavonoids on human liver microsomes and for 8 flavonoids it was characterized on recombinant cytochromes P450
While human liver microsomes catalyze the aromatic hydroxylation of the ring B, CYP1A2 catalyses the aromatic hydroxylation at the ring A with catalytic effectiveness of (1.5 ± 0.9) × 106 M–1 min–1
Summary
M ETABOLISM is one of the ways by which human organisms protect themselves from foreign substances i.e. xenobiotics. The liver microsomal cytochrome P450 have important role in determining the intensity and duration of the drug effect and play a key role in the detoxification of xenobiotics.[2] The total number of cytochrome P450 substrates reaches several thousand. The cytochrome P450 enzyme system has a role in the metabolism of specific endogenous substrates such as fatty acids, steroid hormones and eicosanoids While this is mainly attributed to mitochondrial cytochrome P450, microsomal cytochromes P450 have a main purpose to clean the body from ingested foreign substances such as terpenes, alkaloids, pyrolysis products, and other xenobiotics.[1,2,3]
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