New insights in bilirubin metabolism and their clinical implications

作     者：Eva Sticova Milan Jirsa 

作者机构：Centre for Experimental MedicineInstitute for Clinical and Experimental Medicine14021 Prague 4Czech Republic Third Faculty of MedicineCharles University10000 Prague 10Czech Republic 

出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)

年 卷 期：2013年第19卷第38期

页      面：6398-6407页

核心收录：

学科分类：1010[医学-医学技术（可授医学、理学学位）] 10[医学] 

基　　金：Supported by The Project(Ministry of Health Czech Republic)for Development of Research Organization 00023001(IKEM Prague Czech Republic) Institutional support 

主　　题：Hyperbilirubinemia Hereditary jaundice UGT1A1 ABCC2 Organic anion transporting polypeptide 1B1 Organic anion transporting polypeptide 1B3 

摘      要：Bilirubin,a major end product of heme breakdown,is an important constituent of bile,responsible for its characteristic *** recent decades,our understanding of bilirubin metabolism has expanded along with the processes of elimination of other endogenous and exogenous anionic substrates,mediated by the action of multiple transport systems at the sinusoidal and canalicular membrane of *** inherited disorders characterised by impaired bilirubin conjugation(Crigler-Najjar syndrome typeⅠand typeⅡ,Gilbert syndrome)or transport(Dubin-Johnson and Rotor syndrome)result in various degrees of hyperbilirubinemia of either the predominantly unconjugated or predominantly conjugated ***,disrupted regulation of hepatobiliary transport systems can explain jaundice in many acquired liver *** this review,we discuss the recent data on liver bilirubin handling based on the discovery of the molecular basis of Rotor *** data show that a substantial fraction of bilirubin conjugates is primarily secreted by MRP3 at the sinusoidal membrane into the blood,from where they are subsequently reuptaken by sinusoidal membrane-bound organic anion transporting polypeptides OATP1B1 and ***1B proteins are also responsible for liver clearance of bilirubin conjugated in splanchnic organs,such as the intestine and kidney,and for a number of endogenous compounds,xenobiotics and *** of one or both OATP1B proteins thus may have serious impact on toxicity of commonly used drugs cleared by this system such as statins,sartans,methotrexate or *** liverblood cycling of conjugated bilirubin is impaired in cholestatic and parenchymal liver diseases and this impairment most likely contributes to jaundice accompanying these disorders.