Conjugation position of quercetin glucuronides and effect on biological activity.
Quercetin glycosides are common dietary antioxidants. In general, however, potential biological effects of the circulating plasma metabolites (e.g., glucuronide conjugates) have not been measured. We have determined the rate of glucuronidation of quercetin at each position on the polyphenol ring by human liver cell-free extracts containing UDP-glucuronosyltransferases. The apparent affinity of UDP-glucuronosyltransferase followed the order 4'- > 3'- > 7- > 3, although the apparent maximum rate of formation was for the 7-position. The 5-position did not appear to be a site for conjugation. After isolation of individual glucuronides, the inhibition of xanthine oxidase and lipoxygenase were assessed. The K(i) for the inhibition of xanthine oxidase by quercetin glucuronides followed the order 4'- > 3'- > 7- > 3-, with quercetin-4'-glucuronide a particularly potent inhibitor (K(i) = 0. 25 microM). The glucuronides, with the exception of quercetin-3-glucuronide, were also inhibitors of lipoxygenase. Quercetin glucuronides are metabolites of quercetin in humans, and these compounds can retain some biological activity depending on conjugation position at expected plasma concentrations.
Day
A J
AJ
Diet, Health and Consumer Sciences Division, Institute of Food Research, Norwich Research Park, Colney, Norwich, UK.
Bao
Y
Y
Morgan
M R
MR
Williamson
G
G
D020719:Glucuronides / Q000494:pharmacology*; D014453:Glucuronosyltransferase / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008084:Lipoxygenase / Q000378:metabolism*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology; D015394:Molecular Structure; D011794:Quercetin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology*; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors*
D020719:Glucuronides; D016859:Lipoxygenase Inhibitors; D011794:Quercetin; D008084:Lipoxygenase; D014969:Xanthine Oxidase; D014453:Glucuronosyltransferase