title: Flavonoid glucuronides are substrates for human liver beta-glucuronidase.
abstract: Quercetin glucuronides are the main circulating metabolites of quercetin in humans. We hypothesise that the potential availability of the aglycone within tissues depends on the substrate specificity of the deconjugating enzyme beta-glucuronidase towards circulating flavonoid glucuronides. Human tissues (small intestine, liver and neutrophils) exhibited beta-glucuronidase against quercetin glucuronides. The various quercetin glucuronides were deconjugated at similar rates, but liver cell-free extracts were the most efficient and the activity was completely inhibited by saccharo-1,4-lactone (a beta-glucuronidase inhibitor). Furthermore, pure recombinant human beta-glucuronidase hydrolysed various flavonoid glucuronides, with a 20-fold variation in catalytic efficiency (k(cat)/K(m)=1.3x10(3) M(-1) s(-1) for equol-7-O-glucuronide and 26x10(3) M(-1) s(-1) for kaempferol-3-O-glucuronide). Similar catalytic efficiencies were obtained for quercetin O-glucuronides substituted at different positions. These results show that flavonoid glucuronides can be deconjugated by microsomal beta-glucuronidase from various human cells.
authors.affiliation: Nutrition, Health and Consumer Sciences Division, Institute of Food Research, Norwich, UK.
authors.forename: K A
authors.initials: KA
authors.lastname: O'Leary
authors.forename: A J
authors.initials: AJ
authors.lastname: Day
authors.forename: P W
authors.initials: PW
authors.lastname: Needs
authors.forename: W S
authors.initials: WS
authors.lastname: Sly
authors.forename: N M
authors.initials: NM
authors.lastname: O'Brien
authors.forename: G
authors.initials: G
authors.lastname: Williamson
mesh_terms: D002851:Chromatography, High Pressure Liquid; D005419:Flavonoids / Q000378:metabolism*; D005966:Glucuronidase / Q000378:metabolism*; D020719:Glucuronides / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D011994:Recombinant Proteins / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D005419:Flavonoids; D020719:Glucuronides; D011994:Recombinant Proteins; D005966:Glucuronidase