Effect of a conserved mutation in uridine diphosphate glucuronosyltransferase 1A1 and 1A6 on glucuronidation of a metabolite of flutamide

被引：0

作者：

Masaki Ito

Kazuo Yamamoto

Yoshihiro Maruo

Hiroshi Sato

Yoshihide Fujiyama

Tadao Bamba

机构：

[1] Second Department of Internal Medicine,

[2] Shiga University of Medical Science,undefined

[3] Seta,undefined

[4] Otsu,undefined

[5] Shiga,undefined

[6] Japan,undefined

[7] Department of Pediatrics,undefined

[8] Shiga University of Medical Science,undefined

[9] Seta,undefined

[10] Otsu,undefined

[11] Shiga,undefined

[12] Japan,undefined

[13] Department of Biology,undefined

[14] Shiga University of Medical Science,undefined

[15] Seta,undefined

[16] Otsu,undefined

[17] Shiga,undefined

[18] Japan,undefined

来源：

European Journal of Clinical Pharmacology | 2002年 / 58卷

关键词：

Uridine diphosphate glucuronosyltransferase Glucuronidation Flutamide;

D O I：

暂无

中图分类号：

学科分类号：

摘要：

Objective: We investigated how the conserved mutation (Y486D) changed the kinetic parameters of uridine diphosphate glucuronosyltransferase 1A1 and 1A6 (UGT1A1 and 1A6) for 2-amino-5-nitro-4-trifluoromethylphenol, which is a major metabolite of flutamide, a nonsteroidal antiandrogenic agent. Methods: The wild-type or mutant cDNA-expressed UGT was co-incubated with 2-amino-5-nitro-4-trifluoromethylphenol (aglycone) and uridine diphosphate–glucuronic acid (UDP–GA, donor substrate). The glucuronidation of the aglycone was determined. Results: The maximum velocities of the mutant UGT1A1 and UGT1A6 were about 12% and less than 1% of the corresponding wild-type, respectively. The Michaelis constant (KM) for the aglycone of the wild-type UGT1A1 was double that of the mutant, but the KM for UDP–GA of the wild-type UGT1A1 was not significantly different from that of the mutant. Conclusion: Patients with Y486D may accumulate excessive 2-amino-5-nitro-4-trifluoromethylphenol, which might lead to unexpected toxicity.

引用

页码：11 / 14

页数：3