TitleFormation of (2)- and (2)-8-Prenylnaringenin Glucuronides by Human UDP-Glucuronosyltransferases.
Publication TypeJournal Article
Year of Publication2019
AuthorsFang J-B, Nikolic D, Lankin DC, Simmler C, Chen S-N, Alvarenga RFRamos, Liu Y, Pauli GF, van Breemen RB
JournalJ Agric Food Chem
Date Published2019 Oct 23
KeywordsBiocatalysis, Flavanones, Glucuronides, Glucuronosyltransferase, Humans, Humulus, Mass Spectrometry, Microsomes, Liver, Plant Extracts, Stereoisomerism

Occurring in hops () and beer as a racemic mixture, (2,2)-8-prenylnaringenin (8-PN) is a potent phytoestrogen in hop dietary supplements used by women as alternatives to conventional hormone therapy. With a half-life exceeding 20 h, 8-PN is excreted primarily as 8-PN-7--glucuronide or 8-PN-4'--glucuronide. Human liver microsomes and 11 recombinant human UDP-glucuronosyltransferases (UGTs) were used to catalyze the formation of the two oxygen-linked glucuronides of purified (2)8PN and (2)8-PN, which were subsequently identified using mass spectrometry and nuclear magnetic resonance spectroscopy. Formation of (2)- and (2)-8-PN-7--glucuronides predominated over the 8-PN-4'-glucuronides except for intestinal UGT1A10, which formed more (2)-8-PN-4'--glucuronide. (2)-8-PN was a better substrate for all 11 UGTs except for UGT1A1, which formed more of both (2)-8-PN glucuronides than (2)-8-PN glucuronides. Although several UGTs conjugated both enantiomers of 8-PN, some conjugated just one enantiomer, suggesting that human phenotypic variation might affect the routes of metabolism of this chiral estrogenic constituent of hops.

Alternate JournalJ. Agric. Food Chem.
PubMed ID31554401
PubMed Central IDPMC6942495
Grant ListP41 GM068944 / GM / NIGMS NIH HHS / United States
P50 AT000155 / AT / NCCIH NIH HHS / United States
S10 RR023785 / RR / NCRR NIH HHS / United States