Brunelle F M, Raoof A A, de ville de Goyet J, Verbeeck R K
Pharmacokinetics Laboratory, School of Pharmacy, University Hospital St. Luc, Catholic University of Louvain, Brussels, Belgium.
Biopharm Drug Dispos. 1996 May;17(4):311-7. doi: 10.1002/(SICI)1099-081X(199605)17:4<311::AID-BDD953>3.0.CO;2-V.
In vitro glucuronidation was studied in liver microsomes from two patients with Crigler-Najjar type I (CN-I) disease and compared with the activity measured in microsomes prepared from six control human livers. The UDP-glucuronosyltransferase (UGT) activity was determined toward the following substrates: 4-nitrophenol, propofol, (-)-morphine (formation of the 3-glucuronide), and diflunisal (formation of the phenolic and acyl glucuronides). Glucuronidation of 4-nitrophenol was reduced in one of the CN-I livers (CN-I No. 1) (0.9 nmol min(-1)mg(-1)) and normal in the other CN-I liver (CN-I No. 2) (3.5 nmol min(-1) mg(-l)) compared to the control livers (5.6 +/- 29 nmol min(-1) mg(-1)), mean +/- S.D.). Propofol glucuronidation was not detectable (i.e. less than 0.100 nmol min(-l) mg(-1) in the CN-I No. 1 liver and normal in the CN-I No. 2 liver (1.78 nmol min(-1) mg(-1) against 1.52 +/ 0.72 nmol min(-l) mg(-) in the control livers). The glucuronidation of (-)-morphine to the 3-glucuronide and the formation of the phenolic and acyl glucuronides of diflunisal were normal in both CN-I livers compared to the control livers. Our results show that CN-I patients are heterogeneous regarding UGT activity toward the phenolic substances 4-nitrophenol and propofol.
在两名患有I型克里格勒 - 纳贾尔综合征（CN - I）的患者的肝微粒体中研究了体外葡萄糖醛酸化作用，并与从六个对照人肝脏制备的微粒体中测得的活性进行了比较。测定了UDP - 葡萄糖醛酸基转移酶（UGT）对以下底物的活性：4 - 硝基苯酚、丙泊酚、（ - ） - 吗啡（3 - 葡萄糖醛酸苷的形成）和双氯芬酸（酚类和酰基葡萄糖醛酸苷的形成）。与对照肝脏（5.6±2.9 nmol min⁻¹mg⁻¹，平均值±标准差）相比，4 - 硝基苯酚的葡萄糖醛酸化在其中一个CN - I肝脏（CN - I No.1）中降低（0.9 nmol min⁻¹mg⁻¹），而在另一个CN - I肝脏（CN - I No.2）中正常（3.5 nmol min⁻¹mg⁻¹）。丙泊酚的葡萄糖醛酸化在CN - I No.1肝脏中无法检测到（即低于0.100 nmol min⁻¹mg⁻¹），在CN - I No.2肝脏中正常（1.78 nmol min⁻¹mg⁻¹），对照肝脏中为1.52±0.72 nmol min⁻¹mg⁻¹。与对照肝脏相比，在两个CN - I肝脏中，（ - ） - 吗啡向3 - 葡萄糖醛酸苷的葡萄糖醛酸化以及双氯芬酸的酚类和酰基葡萄糖醛酸苷的形成均正常。我们的结果表明，CN - I患者在UGT对酚类物质4 - 硝基苯酚和丙泊酚的活性方面存在异质性。
