Glucuronidation of flavonoids by recombinant UGT1A3 and UGT1A9.
Flavonoids are highlighted for their potential roles in the prevention of oxidative stress-associated diseases. Their metabolisms in vivo, such as glucuronidation, are the key points to determine their health beneficial properties. In this paper, we tested the glucuronidation of nineteen flavonoids by both recombinant human UGT1A3 and UGT1A9. Eleven compounds could be catalyzed by both enzymes. In general, both enzymes showed moderate to high catalyzing activity to most flavonoid aglycones, while the catalyzing efficiency changed with structures. Each flavonoid produced more than one monoglucuronide with no diglucuronide detected by liquid chromatography-mass spectrometry (LC-MS). Enzymatic kinetic analysis indicated that the catalyzing efficiency (Vmax/Km) of UGT1A9 was higher than that of UGT1A3, suggesting its important role in flavonoid glucuronidation. Both human UGT1A3 and UGT1A9 preferred flavonoid aglycone to flavonoid glycoside, and their metabolism to arabinoside was stronger than to other glycosides. Of the flavonoids studied, it is the first time to report isorhamnetin, morin, silybin, kaempferol, daidzein, quercetin-3',4'-OCHO-, quercetin xylopyranoside and avicularin as substrates of UGT1A3. Apigenin, morin, daidzein, quercetin-3',4'-OCHO-, quercetin xylopyranoside and avicularin were the newly reported substrates of UGT1A9.
Department of Drug Metabolism and Pharmaceutical Analysis, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Yakun
Y
Chen
Shenggu
S
Xie
Shuqing
S
Chen
Su
S
Zeng
D000818:Animals; D016367:Baculoviridae / Q000235:genetics; D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D005419:Flavonoids / Q000737:chemistry* / Q000378:metabolism; D005966:Glucuronidase / Q000737:chemistry / Q000378:metabolism*; D020719:Glucuronides / Q000737:chemistry* / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D006801:Humans; D006868:Hydrolysis; D007313:Insecta / Q000821:virology; D007700:Kinetics; D015394:Molecular Structure; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D021241:Spectrometry, Mass, Electrospray Ionization; D014162:Transfection; D000090264:UDP-Glucuronosyltransferase 1A9
D005419:Flavonoids; D020719:Glucuronides; D011994:Recombinant Proteins; C000715591:UGT1A9 protein, human; C122075:UDP-glucuronosyltransferase, UGT1A3; D014453:Glucuronosyltransferase; D000090264:UDP-Glucuronosyltransferase 1A9; D005966:Glucuronidase