McGurk K A, Brierley C H, Burchell B
Department of Molecular and Cellular Pathology, University of Dundee, Ninewells Hospital and Medical School, Scotland, UK.
Biochem Pharmacol. 1998 Apr 1;55(7):1005-12. doi: 10.1016/s0006-2952(97)00534-0.
The UDP-glucuronosyltransferases catalyse the conjugation of glucuronic acid to a wide variety of endobiotics and xenobiotics, representing one of the major conjugation reactions in the conversion of both exogenous (e.g. drugs and pesticides) and endogenous compounds (e.g. bilirubin and steroid hormones). The liver is the major site of glucuronidation, however a number of extrahepatic tissues exhibit particular UDP-glucuronosyltransferase activities. The present study was undertaken to assess the human renal UDP-glucuronosyltransferase system. Enzymatic analysis of human kidney showed that a limited number of UDP-glucuronosyltransferase isoforms were expressed in this tissue. However the level of renal UGT activity towards the anaesthetic propofol was higher compared with human liver. The glucuronidation of propofol is catalysed by UGT1A8/9 suggesting higher levels of this isoform in the kidney. Immunoblot analysis revealed two major UDP-glucuronosyltransferase immunopositive bands to be present in human kidney as compared to four major bands in human liver. The human kidney was capable of conjugating various structurally diverse drugs and xenobiotics.
UDP-葡萄糖醛酸基转移酶催化葡萄糖醛酸与多种内源性物质和外源性物质结合，这是外源性化合物（如药物和农药）和内源性化合物（如胆红素和甾体激素）转化过程中的主要结合反应之一。肝脏是葡萄糖醛酸化的主要部位，然而许多肝外组织也表现出特定的UDP-葡萄糖醛酸基转移酶活性。本研究旨在评估人肾UDP-葡萄糖醛酸基转移酶系统。对人肾的酶分析表明，该组织中表达的UDP-葡萄糖醛酸基转移酶同工型数量有限。然而，与人类肝脏相比，肾脏对麻醉药丙泊酚的UGT活性水平更高。丙泊酚的葡萄糖醛酸化由UGT1A8/9催化，这表明该同工型在肾脏中的水平更高。免疫印迹分析显示，与人类肝脏中的四条主要条带相比，人肾中存在两条主要的UDP-葡萄糖醛酸基转移酶免疫阳性条带。人肾能够结合各种结构不同的药物和外源性物质。
