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Glucuronidation of bioflavonoids by human UGT1A10: structure-function relationships.
R H Lewinsky1, P A Smith, P I Mackenzie
1Department of Clinical Pharmacology, Flinders University School of Medicine, Flinders Medical Centre, Bedford Park, SA, Australia.
Summary
The human UDP glucuronosyltransferase 1A10 (UGT1A10) enzyme metabolizes dietary bioflavonoids. Structural features like hydroxyl groups on the A-ring are key for UGT1A10 to act as a substrate.
Area of Science:
- Pharmacology
- Biochemistry
- Drug Metabolism
Background:
- Extrahepatic human UDP glucuronosyltransferase 1A10 (UGT1A10) is present in the gastrointestinal tract.
- UGT1A10 is involved in eliminating orally ingested lipophilic compounds.
- The substrate specificity of UGT1A10 for these compounds, particularly bioflavonoids, is not fully understood.
Purpose of the Study:
- To characterize the structural features of bioflavonoids that enable them to be substrates for UGT1A10.
- To understand the role of UGT1A10 in the metabolism of dietary bioflavonoids.
Main Methods:
- Investigated the glucuronidation of various bioflavonoids by UGT1A10.
- Analyzed the impact of hydroxyl group positions and other substituents on the A-ring and B-ring of bioflavonoids on UGT1A10 activity.
Main Results:
- UGT1A10 prefers substrates with hydroxyl groups at C6 or C7 of the A-ring, but not at C5.
- Glucuronidation is hindered by hydroxyl groups on the B-ring (C4') and by sugar moieties.
- Increased activity was observed with up to two additional hydroxyl groups on the A-ring.
Conclusions:
- Specific hydroxyl group placement on the A-ring is crucial for bioflavonoid glucuronidation by UGT1A10.
- UGT1A10 significantly contributes to the gastrointestinal metabolism of dietary bioflavonoids.
- Understanding these interactions is vital for predicting the metabolic fate of dietary compounds.