Linked Life Data

17991766

Source:http://linkedlifedata.com/resource/pubmed/id/17991766

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2008-1-25
pubmed:abstractText
The dietary polyphenol trans-resveratrol (3,5,4'-trihydroxy-trans-stilbene) is glucuronidated at the 3 and 4' positions to yield two major glucuronide conjugates, resveratrol-3-O-glucuronide (R3G) and resveratrol-4'-O-glucuronide (R4'G). The major enzymes catalyzing this conjugation reaction are members of the UDP-glucuronosyl transferase (UGT) 1A family and include UGT1A1 and UGT1A9, with minor contributions by UGT1A10. The kinetics of resveratrol glucuronidation in these three UGT1A isoforms as well as in human liver and intestinal microsomes were characterized across a wide concentration range. Atypical kinetics were observed for resveratrol glucuronidation in all the protein sources studied. The V(max) estimate per total protein for both glucuronides was higher in human intestinal microsomes compared with human liver microsomes (12.2 +/- 0.34 versus 7.4 +/- 0.25 nmol/min/mg for R3G and 8.9 +/- 0.14 versus 0.45 +/- 0.01 nmol/min/mg for R4'G). The kinetic profile for formation of R3G in both human liver and intestinal microsomes fits a substrate inhibition model, whereas that for R4'G exhibited a biphasic kinetic profile in human liver microsomes and substrate inhibition in human intestinal microsomes. In recombinant human UGT supersomes, for both glucuronides, UGT1A9 exhibited higher activity than UGT1A1, whereas the lowest activity was observed with UGT1A10. The kinetic profile for R3G exhibited substrate inhibition for all three isoforms, whereas that for R4'G differed, exhibiting substrate inhibition for UGT1A1 and UGT1A10 and Hill kinetics for UGT1A9. These results suggest that in vitro kinetics of resveratrol glucuronidation at high concentrations cannot be ignored in predicting in vivo clearance upon high-dose consumption of resveratrol.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1521-009X
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
36
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
322-30
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Resveratrol (trans-resveratrol, 3,5,4'-trihydroxy-trans-stilbene) glucuronidation exhibits atypical enzyme kinetics in various protein sources.
pubmed:affiliation
Department of Pharmaceutical Sciences, Temple University, Philadelphia, Pennsylvania 19140, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't