Bas i s stud i es on the appropr i ate usage of c l i n i ca I med i c i ne : i so form specificity of the functional interaction between drug metabolizing enzymes and the individual differences

临床用药合理使用的基础研究：形成药物代谢酶功能相互作用的特异性和个体差异

• 批准号: 21590164
• 负责人: ISHII Yuji
• 金额: $ 2.91万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21590164/
• 关键词: 薬物代謝; UDP-グルクロン酸転移酵素; グルクロン酸抱合; シトクロムP450; タンパク質間相互作用

Interaction between cytochP4so P450 CYPsA4YP3A4) and UDPglucuronosyltransferase(UGT) isoforms in COS cells was evidenced by an analysis using Fluorescence Resonance Energy Transfer. FurtCYPsA4YP3A4 affects the glucuronidation activity catalyzeUGTlAiGT1A7 and 1A3. However, the modifying effecCYPsA4YP3A4 differed between UGT isoforms. In addition, differences were also seen in the effecCYPsA4YP3AUGTlAiGT1A7 variants* 1,* 2 and* 3. Therefore, these results support the hypothesis that the interaction betCYPsA4YP3A4 and UGT is one of the determinants involved in the interindividual difference in glucuronidation. On the other hand, it is also suggested that some of the endogenous and foodderived compounds modulate UGT activity.

通过荧光共振能量转移分析证实了COS细胞中细胞chp4so P450 CYPsA4YP3A4和UDPglucuronosyltransferase（UGT）亚型之间的相互作用。FurtCYPsA4YP3A4影响葡萄糖醛酸化活性的催化剂zeugtlaigt1a7和1A3。然而，UGT同工异构体对cypsa4yp3a4的修饰效果不同。此外，effecCYPsA4YP3AUGTlAiGT1A7变异* 1、* 2和* 3也存在差异。因此，这些结果支持了cypsa4yp3a4和UGT之间的相互作用是葡萄糖醛酸化个体间差异的决定因素之一的假设。另一方面，也表明一些内源性和食物来源的化合物调节UGT活性。

项目成果

脂肪酸および脂肪酸CoAがモルヒネグルクロン酸抱合活性に及ぼす影響

脂肪酸和脂肪酸CoA对吗啡葡萄糖醛酸化活性的影响

• 发表时间: 2009
• 作者: 石井祐次;Arief Nurrochmad;山田英之
• 通讯作者: 山田英之

Hetero-Oligomerization of UDP-Glucuronosyltransferases and Cytochrome P450 3A4 : Analysis by Fluorescence Resonance Energy Transfer (FRET) and Modulation of CYP3A4 activity by UGTs

UDP-葡萄糖醛酸基转移酶和细胞色素 P450 3A4 的异源寡聚：荧光共振能量转移 (FRET) 分析和 UGT 对 CYP3A4 活性的调节

• 发表时间: 2011
• 作者: Yuu Miyauchi;Yuji Ishii;Toshiya Oizaki;Yasushi Yamazoe;Kiyoshi Nagata;Peter I.Mackenzie;Hideyuki Yamada
• 通讯作者: Hideyuki Yamada

Effect of Cytochrome P450 3A4 on the Function of UDP-Glucuronosyltransferase 1A3 : Alteration of Affinity toward UDP-Glucuronic acid

细胞色素 P450 3A4 对 UDP-葡萄糖醛酸基转移酶 1A3 功能的影响：改变对 UDP-葡萄糖醛酸的亲和力

• 发表时间: 2011
• 作者: Kousuke Kinoshita;Yuji Ishii;Yuu Miyauchi;Toshiya Oizaki;Shin-ichi Ikushiro;Yasushi Yamazoe;Kiyoshi Nagata;Peter I.Mackenzie;Hideyuki Yamada
• 通讯作者: Hideyuki Yamada

UDP-グルクロン酸転移酵素1A7の遺伝的多型と触媒活性:シトクロムP450 3A4 共発現による影響

UDP-葡萄糖醛酸基转移酶 1A7 的遗传多态性和催化活性：细胞色素 P450 3A4 共表达的影响

• 发表时间: 2010
• 作者: 古葉弘樹;石井祐次;追崎俊也;竹田修三;生城真一;永田清;山添康;Peter I.Mackenzie;山田英之
• 通讯作者: 山田英之

Toshiya Oizaki, Yasushi Yamazoe, Kiyoshi Nagata, Peter I. Mackenzie, HideyukiYamada, Hetero-Oligomerization of UDP-Glucuronosyltransferases and CytochroP4so450 3A4 : Analysis by Fluorescence Resonance Energy Transfer(FRET) and Modulation of CYPsA43A4 acti

Toshiya Oizaki，Yasushi Yamazoe，Kiyoshi Nagata，Peter I. Mackenzie，HideyukiYamada，UDP-葡萄糖醛酸基转移酶和 CytochroP4so450 3A4 的异源寡聚：荧光共振能量转移（FRET）分析和 CYPsA43A4 acti 的调制

• 发表时间: 2011
• 作者: Yuu Miyauchi;Yuji Ishii
• 通讯作者: Yuji Ishii