Glucuronidation activity of the UGT2B17 enzyme toward xenobiotics

被引：77

作者：

Turgeon, D ^{[1
]}

Carrier, JS ^{[1
]}

Chouinard, S ^{[1
]}

Bélanger, A ^{[1
]}

机构：

[1] CHU Laval, Res Ctr, Oncol & Mol Endocrinol Res Ctr, Quebec City, PQ G1V 4G2, Canada

来源：

DRUG METABOLISM AND DISPOSITION | 2003年 / 31卷 / 05期

关键词：

D O I：

10.1124/dmd.31.5.670

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

UDP-glucuronosyltransferase (UGT) 2B17 is one of the most important conjugating enzymes in androgen metabolism and shares more than 95% homology with UGT2B15. Although UGT2B15 has been fully characterized for its ability to conjugate drugs, environmental pollutants, and dietary components, UGT2B17 received less attention for its capacity to glucuronidate xenobiotics. In the present study, more than 55 exogenous compounds belonging to several categories of compounds were analyzed as potential substrates for UGT2B17. Glucuronidation activity was observed with several coumarins, anthraquinones, and flavonoids. The higher glucuronidation activity was measured with alizarin ( 125 pmol . min(-1). mg protein(-1)), whereas UGT2B17 conjugated eugenol, scopoletin, and galangin with glucuronidation rates of 102.5, 102, and 58 pmol . min(-1) . mg protein(-1), respectively. The characterization of UGT2B17 as a xenobiotics- conjugating enzyme demonstrates that its role is not limited to androgen metabolism and that its specificity for exogenous substrates is different from other UGT2B isoforms. Taken together, these data suggest a role of UGT2B17 for the hepatic detoxification.

引用

页码：670 / 676

页数：7

共 39 条

[31] Glucuronidation versus oxidation of the flavonoid galangin by human liver microsomes and hepatocytes [J].

Otake, Y ;

Hsieh, F ;

Walle, T .

DRUG METABOLISM AND DISPOSITION, 2002, 30 (05) :576-581

[32] GENE STRUCTURE AT THE HUMAN UGT1 LOCUS CREATES DIVERSITY IN ISOZYME STRUCTURE, SUBSTRATE-SPECIFICITY, AND REGULATION [J].

OWENS, IS ;

RITTER, JK .

PROGRESS IN NUCLEIC ACID RESEARCH AND MOLECULAR BIOLOGY, VOL 51, 1995, 51 :305-338

[33]

RITTER JK, 1990, J BIOL CHEM, V265, P7900

[34]

Schapira DV, 1999, ONCOL REP, V6, P433

[35] INVESTIGATION OF THE SUBSTRATE-SPECIFICITY OF A CLONED EXPRESSED HUMAN BILIRUBIN UDP-GLUCURONOSYLTRANSFERASE - UDP-SUGAR SPECIFICITY AND INVOLVEMENT IN STEROID AND XENOBIOTIC GLUCURONIDATION [J].

SENAFI, SB ;

CLARKE, DJ ;

BURCHELL, B .

BIOCHEMICAL JOURNAL, 1994, 303 :233-240

[36] Antiinflammatory activity of coumarins from Santolina oblongifolia [J].

Silvan, AM ;

Abad, MJ ;

Bermejo, P ;

Sollhuber, M ;

Villar, A .

JOURNAL OF NATURAL PRODUCTS, 1996, 59 (12) :1183-1185

[37] Inhibition of proliferation of estrogen receptor-positive MCF-7 human breast cancer cells by flavonoids in the presence and absence of excess estrogen [J].

So, FV ;

Guthrie, N ;

Chambers, AF ;

Carroll, KK .

CANCER LETTERS, 1997, 112 (02) :127-133

[38] Relative enzymatic activity, protein stability, and tissue distribution of human steroid-metabolizing UGT2B subfamily members [J].

Turgeon, D ;

Carrier, JS ;

Lévesque, É ;

Hum, DW ;

Bélanger, A .

ENDOCRINOLOGY, 2001, 142 (02) :778-787

[39]

Turgeon N, 2000, Transpl Infect Dis, V2, P2, DOI 10.1034/j.1399-3062.2000.020102.x

← 1 2 3 4 →