Troglitazone glucuronidation在人类肝脏和肠微粒体:高催化活性UGT1A8 UGT1A10。

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Troglitazone glucuronidation在人类肝脏和肠微粒体:高催化活性UGT1A8 UGT1A10。

药物金属底座Dispos。2002; 12月30 (12):1462 - 9。

PubMed ID

12433820 (在PubMed

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文摘

Troglitazone glucuronidation在人类肝脏和肠微粒体和重组UDP-glucuronosyltransferases (ugt)彻底的特点。所有重组UGT baculovirus-infected昆虫细胞亚型(UGT1A1、UGT1A3 UGT1A4, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT1A10, UGT2B7,和UGT2B15)展出troglitazone glucuronosyltransferase活动。特别是UGT1A8和UGT1A10,表示在肝外组织如胃、小肠、结肠,表现出高的催化活性,其次是UGT1A1 UGT1A9。在重组的动力学troglitazone glucuronidation UGT1A10 UGT1A1表现出一种典型模式,当底物浓度底物抑制超过200微M . Michaelis-Menten方程在6到200微troglitazone, K (M)值为11.1 + / - 5.8微M和V (max)值为33.6 + / - 3.7 pmol /分钟/ mg UGT1A10重组蛋白。在重组UGT1A1, K (m)值为58.3 + / - 29.2微m和V (max)值为12.3 + / - 2.5 pmol /分钟/毫克的蛋白质。的动力学troglitazone glucuronidation在人类肝脏和空肠微粒体也表现出一种典型模式。K (m)值为13.5 + / - 2.0微m和V (max)值为34.8 + / - 1.2 pmol /分钟/ mg troglitazone glucuronidation在人类肝微粒体,和K (m)值为8.1 + / - 0.3微m和V (max)是700.9 + / - 4.3 pmol /分钟/毫克蛋白在人类空肠微粒体。当内在的间隙与体外动力学参数估计,微粒体蛋白质含量,和体重的组织,troglitazone glucuronidation在人类肠道在人类肝脏高出三倍。个人间的差异troglitazone glucuronosyltransferase活动最多13人肝微粒体的2.2倍。的troglitazone glucuronosyltransferase活动显著(r = 0.579, p < 0.05)与beta雌二醇3-glucuronosyltransferase活动,主要由UGT1A1催化。 The troglitazone glucuronosyltransferase activity in pooled human liver microsomes was strongly inhibited by bilirubin (IC(50) = 1.9 micro M), a typical substrate of UGT1A1. These results suggested that the troglitazone glucuronidation in human liver would be mainly catalyzed by UGT1A1. Interindividual differences in the troglitazone glucuronosyltransferase activity in S-9 samples from five human intestines was 8.2-fold. The troglitazone glucuronosyltransferase activity in human jejunum microsomes was strongly inhibited by emodin (IC(50) = 15.6 micro M), a typical substrate of UGT1A8 and UGT1A10, rather than by bilirubin (IC(50) = 154.0 micro M). Therefore, it is suggested that the troglitazone glucuronidation in human intestine might be mainly catalyzed by UGT1A8 and UGT1A10.

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药物酶

药物	酶	类	生物	药理作用	行动
Troglitazone	UDP-glucuronosyltransferase 1 - 1	蛋白质	人类	未知的	底物	细节
Troglitazone	UDP-glucuronosyltransferase 1 - 10	蛋白质	人类	未知的	底物	细节
Troglitazone	UDP-glucuronosyltransferase 1 - 3	蛋白质	人类	未知的	底物	细节
Troglitazone	UDP-glucuronosyltransferase 1 - 4	蛋白质	人类	未知的	底物	细节
Troglitazone	UDP-glucuronosyltransferase 1 - 6	蛋白质	人类	未知的	底物 抑制剂	细节
Troglitazone	UDP-glucuronosyltransferase 1 - 7	蛋白质	人类	未知的	底物	细节
Troglitazone	UDP-glucuronosyltransferase 1 - 8	蛋白质	人类	未知的	底物	细节
Troglitazone	UDP-glucuronosyltransferase 1 - 9	蛋白质	人类	未知的	底物	细节
Troglitazone	UDP-glucuronosyltransferase 2去往b15	蛋白质	人类	未知的	底物	细节
Troglitazone	UDP-glucuronosyltransferase 2 b7	蛋白质	人类	未知的	底物	细节