UGT酶与N-萄糖醛酸结合反应

Conjugation Reaction of UGTs and N-glucuronic Acid

许多含伯胺、仲胺和叔胺的的化学物质与葡糖醛酸结合能形成N-葡糖醛酸代谢物。大约30余种UDP-葡糖醛酸转移酶已经被纯化,或克隆与表达,其中一些可以催化伯胺和叔胺的N-葡醛酸结合反应。UGT1的基因突变,致使一些物种不能形成季铵葡醛酸结合物。研究UGT同工酶对致癌芳杂环胺的代谢产物的催化活性,对于了解这些化合物的致癌危险性具有很大的意义。致癌的芳杂环胺通过代谢成为N-羟化物后,产生基因毒性,UDP-葡糖醛酸转移酶和母体胺结合或与N-羟化代谢物结合形成N-羟化胺类的N-葡醛酸苷,使之代谢失活,或产生稳定的结合物后转移到靶相组织(膀胱),进一步变成有活性的代谢物。

Conjugation of many primary, secondary, and tertiary amine-containing xenobiotics with glucuronic acid can result in the formation of N-glucuronide metabolites. Of the more than 30 UDP-glucuronosyltransferases (UGTs) that have been purified or cloned and expressed, some UGTs many catalyze N-glucuronide formation for primary and secondary amine substrates. The mutation of the UGT1 gene complex may explain the inability of some species to form quaternary ammonium-linked glucuronides. The study of reactivity of UGT isoforms to carcinogenic aromatic amines could serve to broaden our understanding the dangerous carcinogenicity of these compounds. For the N-hydroxylated metabolites of carcinogenic arylamines , N-glucuronidation can result in the formation of either inactive metabolites or liable conjugates which can be transported to their target tissue(urinary bladder)where they may be converted to reactive metabolites.