Naslov
Cytochrome P450 3A4 mediated metabolism of flavonoids

Autori
Žuntar, Irena ; Benković, Goran ; Rimac, Hrvoje ; Bojić, Mirza

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, ostalo

Izvornik
Abstracts of the Food Safety and Quality Congress with international participation - New Achievements and Future Challenges / Šostar, Zvonimir - Opatija : Institut za medicinska istraživanja i medicinu rada, 2017, 65-65

Skup
Food Safety and Quality Congress with international participation - New Achievements and Future Challenges

Mjesto i datum
Opatija, Hrvatska, 21.11.2017. - 24.11.2017

Vrsta sudjelovanja
Poster

Vrsta recenzije
Domaća recenzija

Ključne riječi
Cytochrome P450, flavonoids, metabolism, HPLC, DAD, MS, kinetics

Sažetak
Flavonoids are diverse class of compound to which we are exposed through foods we ingest i.e. vegetables and fruits. Human body perceives flavonoids as xenobiotics that should be metabolized and excreted. Most of xenobiotics first undergo oxidation reactions that are primarily catalyzed by cytochromes P450. Major enzyme involved in oxidations of more than one third of xenobiotics is cytochrome P450 3A4. This enzyme is abundant in enterocytes and hepatocytes and serves to prevent xenobiotic absorption and facilitate elimination. Objective of this work was to determine catalytic efficacy based on Michaelis-Menten kinetic data at which cytochrome P450 3A4 biotransforms flavonoids that were screened out of 30 representative flavonoids. In principle, flavonoids were incubated in 2 to 200 µM range with 5 pmol of baculosme enzyme system containing P450 3A4, NADPH reductase and cytochrome b5 in water media containing phosphate buffer pH 7.4. Reaction was initiated by addition of 15% NADPH generating system. Incubation run for 15 min in shaking water bath at 37 ⁰C and was stop by acidified acetonitrile. Mixture was centrifuged and supernatant was directly analyzed. Structure of metabolite was determined based on comparison of retention time, UV-Vis spectra, precise mass data based on TOF MS as well fragmentation pattern. As flavonoids are mostly UV active quantification was based on DAD data. Data was plotted against Michaelis- Menten curve from which kinetic parameters were determined. Analyzed flavonoids had kcat values ranging from 0.4 to 13.8 pmol/pmol/min and Km values of 40-112 µM. Catalytic efficacy was between (0.05-0.21) x 106 min-1M-1. This data indicates that some flavonoids undergo extensive metabolism mediated by cytochrome P450 3A4. As this enzyme presents most significant enzyme for metabolism of xenobiotics including drugs and toxic substances, it can be presumed that some flavonoids can interfere with metabolism of othes xenobiotics i.e. food-drug interactions.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Farmacija

POVEZANOST RADA