Glucuronides of tea catechins: enzymology of biosynthesis and biological activities.
(-)-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 (V(max)/K(m)) 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 V(max)/K(m) 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 V(max)/K(m) 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.
Lu
Hong
H
Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers the State University of New Jersey, 164 Frelinghuysen Road, Piscataway, NJ 08854, USA.
Meng
Xiaofeng
X
Li
Chuan
C
Sang
Shengmin
S
Patten
Christopher
C
Sheng
Shuqun
S
Hong
Jungil
J
Bai
Naisheng
N
Winnik
Bozena
B
Ho
Chi-Tang
CT
Yang
Chung S
CS
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002392:Catechin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid / Q000295:instrumentation / Q000379:methods; D003110:Colonic Neoplasms; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry / Q000295:instrumentation / Q000379:methods; D020719:Glucuronides / Q000096:biosynthesis* / Q000737:chemistry / Q000494:pharmacology; D014453:Glucuronosyltransferase / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007313:Insecta; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000166:cytology; D007700:Kinetics; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008861:Microsomes / Q000201:enzymology* / Q000378:metabolism; D011837:Radiation-Protective Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity
D020719:Glucuronides; D011837:Radiation-Protective Agents; D016718:Arachidonic Acid; D002392:Catechin; C045651:epigallocatechin gallate; D014453:Glucuronosyltransferase; C057580:gallocatechol