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Human UDP‐glucuronosyltransferases (UGTs) are involved in the metabolism of the natural resveratrol analogues arachidin‐1, arachidin‐3 and piceatannol
Author(s) -
RadominskaPandya Anna,
Nair Vipin,
Bratton Stacie M.,
GallusZawada Anna E.,
Prather Paul L.,
Bolivar Fabricio Medina
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.967.12
Subject(s) - resveratrol , glucuronidation , piceatannol , chemistry , bioavailability , glucuronide , biochemistry , polyphenol , metabolism , pharmacology , kinetics , enzyme , microsome , biology , physics , antioxidant , quantum mechanics
Resveratrol is known to have protective effects against cardiovascular disease, ageing, and cancer. Two natural resveratrol analogs, trans‐Arachidin‐1 and ‐3 (tA1, tA3) were extracted from peanut hairy roots and their glucuronidation was compared to that of trans‐Piceatannol (tPice), a hydroxylated analog of resveratrol that has been shown to be anti‐inflammatoryand anti‐proliferative. The glucuronidation activities of 9 human recombinant UGTs towards these compounds were evaluated using HPLC and LCMS/MS. Single glucuronide products were seen for both tA1 and tA3; while multiple tPice glucuronides were produced. Extrahepatic UGT1A7 and ‐1A10 were found to be the most active and were used for further characterization. UGT1A7 showed Michaelis–Menten kinetics with K m values ranging from 27–56 μM. UGT1A10 demonstrated atypical kinetics toward all three compounds suggesting the presence of multiple binding sites. LCMS/MS assignment of regioselectivity is underway. Our results indicate, for the first time, that lung‐expressed UGT1A7 and intestinal UGT1A10 may contribute significantly to the first pass metabolism of these polyphenols, which can be possible alternatives to resveratrol therapy due to their potential increased bioavailability, a major obstacle to the pharmaceutical use of resveratrol. ( NIH‐GM075893 to AR‐P; NSF‐EPSCoR EPS‐0701890 to FM‐B)