Vertebrate UDP-glucuronosyltransferases: functional and evolutionary aspects

被引:128
作者
Bock, KW [1 ]
机构
[1] Univ Tubingen, Inst Pharmacol & Toxicol, Dept Toxicol, Tubingen, Germany
关键词
vertebrate UDP-glucuronosyltransferases; drug metabolizing enzymes; gastrointestinal barrier; co-regulation of CYPs and UGTs; UDP-glycosyltransferase superfamily;
D O I
10.1016/S0006-2952(03)00296-X
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
UDP-glucuronosyltransferases (UGTs) represent major phase II drug metabolizing enzymes. They are part of a rapidly growing, sequence similarly based superfamily of UDP-glycosyltransferases, including a number of enzymes, which presumably are functionally unrelated to UGTs. The present commentary discusses evolutionary aspects of the large glycosyltransferase superfamily emphasizing functionally related members which share roles in detoxication and elimination of endo- and xenobiotics. The discussion starts with the two human UGT families and polymorphism frequencies in different populations. These families probably evolved in vertebrates as a result of the struggle against toxic phytoalexins at the hepatogastrointestinal barrier. Co-regulation of some UGTs with other drug metabolizing enzymes may also have evolved in the course of 'animal-plant warfare'. Related UDP-glucosyltransferases evolved in insects. Even in plants and bacteria UDP-glucosyltransferases have been characterized which may be functionally related. (C) 2003 Elsevier Science Inc. All rights reserved.
引用
收藏
页码:691 / 696
页数:6
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