Formation of (2R)- and (2S)‑8-Prenylnaringenin Glucuronides by Human UDP-Glucuronosyltransferases

• Published in: Journal of agricultural and food chemistry 2019-10, Vol.67 (42), p.11650-11656
• Main Authors: Fang, Jin-Bo, Nikolić, Dejan, Lankin, David C, Simmler, Charlotte, Chen, Shao-Nong, Ramos Alvarenga, Rene F, Liu, Yang, Pauli, Guido F, van Breemen, Richard B
• Format: Article
• Language: English
• Subjects: Biocatalysis; Flavanones - chemistry; Flavanones - metabolism; Glucuronides - chemistry; Glucuronides - metabolism; Glucuronosyltransferase - chemistry; Glucuronosyltransferase - metabolism; Humans; Humulus - chemistry; Humulus - metabolism; Mass Spectrometry; Microsomes, Liver - chemistry; Microsomes, Liver - metabolism; Plant Extracts - chemistry; Plant Extracts - metabolism; Stereoisomerism
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/acs.jafc.9b04657

Occurring in hops (Humulus lupulus) and beer as a racemic mixture, (2R,2S)-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-O-glucuronide or 8-PN-4′-O-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 (2R)-8-PN and (2S)-8-PN, which were subsequently identified using mass spectrometry and nuclear magnetic resonance spectroscopy. Formation of (2R)- and (2S)-8-PN-7-O-glucuronides predominated over the 8-PN-4′-O-glucuronides except for intestinal UGT1A10, which formed more (2S)-8-PN-4′-O-glucuronide. (2R)-8-PN was a better substrate for all 11 UGTs except for UGT1A1, which formed more of both (2S)-8-PN glucuronides than (2R)-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.