Flavonoid glucuronides are substrates for human liver β‐glucuronidase

FEBS Letters

Sly, William S²  O'Brien, Nora M³  O'Leary, Karen A⁴  Day, Andrea J¹  Needs, Paul W⁴  Williamson, Gary⁴ 

[1] Procter Department of Food Science, University of Leeds, Leeds LS2 9JT, UK;Edward A. Doisy Department of Biochemistry and Molecular Biology, St. Louis University School of Medicine, St. Louis, MO 63104, USA;Nutritional Sciences, Department of Food Science and Technology, University College Cork, Cork, Ireland;Nutrition, Health and Consumer Sciences Division, Institute of Food Research, Norwich Research Park, Colney, Norwich NR4 7UA, UK

关键词: Human;    β-Glucuronidase;    Flavonoid;    Glucuronide;    Quercetin;    Turnover;    UGT;    uridine-diphosphate-glucuronosyltransferase;    p-NPGlcA;    p-nitrophenol glucuronide;    UDPGA;    uridine-diphosphate-glucuronic acid;    ER;    endoplasmic reticulum;   

DOI  :  10.1016/S0014-5793(01)02684-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 β-glucuronidase towards circulating flavonoid glucuronides. Human tissues (small intestine, liver and neutrophils) exhibited β-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 β-glucuronidase inhibitor). Furthermore, pure recombinant human β-glucuronidase hydrolysed various flavonoid glucuronides, with a 20-fold variation in catalytic efficiency (k _cat/K _m=1.3×10³ M⁻¹ s⁻¹ for equol-7-O-glucuronide and 26×10³ 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 β-glucuronidase from various human cells.

【 授权许可】

Unknown