TY - JOUR
T1 - Glucuronides of tea catechins
T2 - Enzymology of biosynthesis and biological activities
AU - Lu, Hong
AU - Meng, Xiaofeng
AU - Li, Chuan
AU - Sang, Shengmin
AU - Patten, Christopher
AU - Sheng, Shuqun
AU - Hong, Jungil
AU - Bai, Naisheng
AU - Winnik, Bozena
AU - Ho, Chi Tang
AU - Yang, Chung S.
PY - 2003/4/1
Y1 - 2003/4/1
N2 - (-)-Epigallocatechin gallate (EGCG) and (-)-epigallocatechin (EGC) are major green tea catechins with antioxidant and anticancer activities. In this study, we characterized the glucuronidation of EGCG and EGC in human, mouse, and rat microsomes and by nine different human UGT 1A and 2B isozymes expressed in insect cells. Six EGCG and EGC glucuronides were biosynthesized, and their structures were identified for the first time. (-)-EGCG-4"-O-glucuronide was the major EGCG glucuronide formed in all incubations. The catalytic efficiency (Vmax/Km) for (-)-EGCG-4"-O-glucuronide formation followed the order: mouse intestine > mouse liver > human liver > rat liver ≫ rat small intestine. The UGT- catalyzed glucuronidation of EGC was much lower than that of EGCG. The Vmax/Km for (-)-EGC-3′-O-glucuronide followed the following order: mouse liver > human liver > rat liver > rat and mouse small intestine. Human UGT1A1, 1A8, and 1A9 had high activities with EGCG. UGT1A8, an intestine-specific UGT, had the highest Vmax/Km for EGCG but low activity with EGC. Mice appeared to be more similar to humans than rats to humans in the glucuronidation of EGCG and EGC. Some of these catechin glucuronides retained the activities of their parent compounds in radical scavenging and in inhibiting the release of arachidonic acid from HT-29 human colon cancer cells. These results provide foundations for understanding the biotransformation and biological activities of tea catechins.
AB - (-)-Epigallocatechin gallate (EGCG) and (-)-epigallocatechin (EGC) are major green tea catechins with antioxidant and anticancer activities. In this study, we characterized the glucuronidation of EGCG and EGC in human, mouse, and rat microsomes and by nine different human UGT 1A and 2B isozymes expressed in insect cells. Six EGCG and EGC glucuronides were biosynthesized, and their structures were identified for the first time. (-)-EGCG-4"-O-glucuronide was the major EGCG glucuronide formed in all incubations. The catalytic efficiency (Vmax/Km) for (-)-EGCG-4"-O-glucuronide formation followed the order: mouse intestine > mouse liver > human liver > rat liver ≫ rat small intestine. The UGT- catalyzed glucuronidation of EGC was much lower than that of EGCG. The Vmax/Km for (-)-EGC-3′-O-glucuronide followed the following order: mouse liver > human liver > rat liver > rat and mouse small intestine. Human UGT1A1, 1A8, and 1A9 had high activities with EGCG. UGT1A8, an intestine-specific UGT, had the highest Vmax/Km for EGCG but low activity with EGC. Mice appeared to be more similar to humans than rats to humans in the glucuronidation of EGCG and EGC. Some of these catechin glucuronides retained the activities of their parent compounds in radical scavenging and in inhibiting the release of arachidonic acid from HT-29 human colon cancer cells. These results provide foundations for understanding the biotransformation and biological activities of tea catechins.
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U2 - 10.1124/dmd.31.4.452
DO - 10.1124/dmd.31.4.452
M3 - Article
C2 - 12642472
AN - SCOPUS:0037378660
SN - 0090-9556
VL - 31
SP - 452
EP - 461
JO - Drug Metabolism and Disposition
JF - Drug Metabolism and Disposition
IS - 4
ER -