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

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