Chowdhury J R, Jansen P L, Fischberg E B, Daniller A, Arias I M
J Clin Invest. 1978 Jul;62(1):191-6. doi: 10.1172/JCI109105.
The microsomal enzyme uridine diphosphate (UDP) glucuronate glucuronyltransferase (E.C. 2.4.1.17) catalyzes formation of bilirubin mono-glucuronide from bilirubin and UDPglucuronic acid. Bilirubin glucuronoside glucuronosyltransferase (E.C. 2.4.1.95), an enzyme concentrated in plasma membrane-enriched fractions of rat liver, converts bilirubin monoglucuronide to bilirubin diglucuronide. Bilirubin glucuronoside glucuronosyltransferase activity was studied in homogenates of liver biopsy specimens obtained from patients with the Crigler-Najjar syndrome (Type I) and in subcellular liver fractions of rats homozygous for UDP glucuronate glucuronyltransferase deficiency (Gunn strain). In patients with the Crigler-Najjar syndrome (Type I) and in Gunn rats, hepatic UDPglucuronate glucuronyltransferase activity was not measurable; however, bilirubin glucuronoside glucuronosyltransferase activity was similar to that in normal controls. The subcellular distribution of bilirubin glucuronoside glucuronosyltransferase activity in Gunn rat liver was similar to the distribution observed in normal Wistar rat liver.When bilirubin monoglucuronide was infused intravenously into Gunn rats, 29+/-5% of the conjugated bilirubin excreted in bile was bilirubin diglucuronide. After transplantation of normal Wistar rat kidney, which contained UDPglucuronate glucuronyltransferase activity, in Gunn rats, the serum bilirubin concentration decreased by 80% in 4 days. The major route of bilirubin removal was biliary excretion of conjugated bilirubin, approximately 70% of which was bilirubin diglucuronide. Although patients with the Crigler-Najjar syndrome (Type I) and Gunn rats lack UDP glucuronate glucuronyltransferase, their livers enzymatically convert bilirubin monoglucuronide to diglucuronide in vitro. Conversion in bilirubin monoglucuronide to diglucuronide was demonstrated in Gunn rats in vivo.
微粒体酶尿苷二磷酸（UDP）葡糖醛酸葡糖醛酸基转移酶（E.C. 2.4.1.17）催化胆红素和UDP葡糖醛酸生成胆红素单葡糖醛酸酯。胆红素葡糖苷葡糖醛酸基转移酶（E.C. 2.4.1.95）是一种集中在大鼠肝脏富含质膜部分的酶，它将胆红素单葡糖醛酸酯转化为胆红素双葡糖醛酸酯。对来自克里格勒 - 纳贾尔综合征（I型）患者的肝活检标本匀浆以及UDP葡糖醛酸葡糖醛酸基转移酶缺乏纯合子大鼠（冈恩品系）的肝脏亚细胞部分中的胆红素葡糖苷葡糖醛酸基转移酶活性进行了研究。在克里格勒 - 纳贾尔综合征（I型）患者和冈恩大鼠中，肝脏UDP葡糖醛酸葡糖醛酸基转移酶活性无法检测到；然而，胆红素葡糖苷葡糖醛酸基转移酶活性与正常对照组相似。冈恩大鼠肝脏中胆红素葡糖苷葡糖醛酸基转移酶活性的亚细胞分布与在正常Wistar大鼠肝脏中观察到的分布相似。当将胆红素单葡糖醛酸酯静脉注入冈恩大鼠时，胆汁中排泄的结合胆红素的29±5%是胆红素双葡糖醛酸酯。在冈恩大鼠中移植含有UDP葡糖醛酸葡糖醛酸基转移酶活性的正常Wistar大鼠肾脏后，血清胆红素浓度在4天内下降了80%。胆红素清除的主要途径是结合胆红素的胆汁排泄，其中约70%是胆红素双葡糖醛酸酯。尽管克里格勒 - 纳贾尔综合征（I型）患者和冈恩大鼠缺乏UDP葡糖醛酸葡糖醛酸基转移酶，但他们的肝脏在体外能将胆红素单葡糖醛酸酯酶促转化为双葡糖醛酸酯。在冈恩大鼠体内也证实了胆红素单葡糖醛酸酯向双葡糖醛酸酯的转化。
