Abstract：
Chlorophenols (CPs) are a group of pollutants that pose a great threat to the environment, they are widely used in industrial and agricultural wastes, pesticides, herbicides, textiles, pharmaceuticals and plastics. Among CPs, pentachlorophenol was listed as one of the persistent organic pollutants (POPs) by the Stockholm convention. This study aims to identify the UDP-glucosyltransferase (UGT) isoforms involved in the metabolic elimination of CPs. CPs\' mono-glucuronide was detected in the human liver microsomes (HLMs) incubation mixture with co-factor uridine-diphosphate glucuronic acid (UDPGA). HLMs-catalyzed glucuronidation metabolism reaction equations followed Michaelis-Menten or substrate inhibition type. Recombinant enzymes and chemical reagents inhibition experiments were utilized to phenotype the main UGT isoforms involved in the glucuronidation of CPs. UGT1A6 might be the major enzyme in the glucuronidation of mono-chlorophenol isomer. UGT1A1, UGT1A6, UGT1A9, UGT2B4 and UGT2B7 were the most important five UGT isoforms for metabolizing the di-chlorophenol and tri-chlorophenol isomers. UGT1A1 and UGT1A3 were the most important UGT isoforms in the catalysis of tetra-chlorophenol and pentachlorophenol isomers. Species differences were investigated using rat liver microsomes (RLMs), pig liver microsomes (PLMs), dog liver microsomes (DLMs), and monkey liver microsomes (MyLMs). All these results were helpful for elucidating the metabolic elimination and toxicity of CPs.
摘要：
氯酚(CPs)是一类对环境造成巨大威胁的污染物,它们广泛用于工业和农业废物，杀虫剂,除草剂,纺织品,药品和塑料。在CP中，《斯德哥尔摩公约》将五氯苯酚列为持久性有机污染物之一。这项研究旨在鉴定参与CPs代谢消除的UDP-葡萄糖基转移酶（UGT）亚型。在人肝微粒体（HLM）与辅助因子尿苷-二磷酸葡萄糖醛酸酸（UDPGA）的孵育混合物中检测到CPs'单葡萄糖醛酸。HLMs催化的葡萄糖醛酸化代谢反应方程式遵循Michaelis-Menten或底物抑制类型。利用重组酶和化学试剂抑制实验对参与CP的葡糖醛酸化的主要UGT同工型进行表型化。UGT1A6可能是单氯苯酚异构体葡糖醛酸化的主要酶。UGT1A1，UGT1A6，UGT1A9，UGT2B4和UGT2B7是代谢二氯酚和三氯酚异构体的最重要的五种UGT同工型。UGT1A1和UGT1A3是催化四氯苯酚和五氯苯酚异构体的最重要的UGT同工型。使用大鼠肝微粒体（RLMs）研究物种差异，猪肝微粒体（PLM），狗肝微粒体（DLM），和猴肝微粒体（MyLMs）。所有这些结果有助于阐明CPs的代谢消除和毒性。
