[Study on human UDP-glucuronosyltransferase (UGT) isoforms involved in in vitro metabolism of trans-resveratrol].
OBJECTIVE
To study major human UGT isoforms involved in trans-resveratrol (TR) phase II metabolism.


METHODS
trans-resveratrol and 12 major human UGT isoforms were incubated in vitro and then glucuronic acid metabolites were determined by HPLC-MS, in order to preliminarily analyze the structure and observe the effect of different UGT isoforms on the generation rate of glucuronic acid metabolites.


RESULTS
In in vitro metabolic system, two metabolites-4'-O-monoglucuronide resveratrol (M-1) and 3-0-monoglucuronide resveratrol (M-2)-were generated from trans-resveratrol after being catalyzed by UGT. During the cause, generation of M-1 and M-2 were catalyzed by UGT1A1, UGT1A3, 1A8, 1A9 andlA10, whereas only UGT1A6 and 1A7 contributed to the forma-tion of M-2. Both the formation rate of M-1 and M-2 catalyzed by UGT1A1, 1A10 and the formation of M-2 catalyzed by UGT1A8 slowed down with the increasing concentration of substrates, causing the phenomenon of "substrate inhibition".


CONCLUSIONS
UGT1A1, 1A8, 1A9, 1A10 get involved in the formation of M-1, and of them UGTIA9 is the most important contributor. UGT1A3 also makes small contribution to the formation of M-1 and M-2, while other UGT isoforms show hardly any reaction with the trans-resveratrol phase II metabolites.
Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China. wangliyan19871012@126.com
Liyan
L
Wang
Aiping
A
Tan
Shan
S
Zhao
Guojun
G
Lv
Xiaojun
X
Ma
D020723:Glucuronic Acid / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D007700:Kinetics; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry* / Q000378:metabolism*
D007527:Isoenzymes; D013267:Stilbenes; D020723:Glucuronic Acid; D014453:Glucuronosyltransferase; D000077185:Resveratrol