Curcumin-glutathione interactions and the role of human glutathione S-transferase P1-1
Curcumin-glutathione interactions and the role of human glutathione S-transferase P1-1
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DOI：
10.1016/s0009-2797(00)00185-x
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发表时间：
2000-08-15
影响因子：
5.1
通讯作者：
Ansari, GAS
中科院分区：
文献类型：
--
作者：
Awasthi, S;Pandya, U;Ansari, GAS
姜黄素(二阿魏酰甲烷)是一种姜黄黄色色素，具有抗氧化特性，动物研究表明它是一种防癌药物。它含有两个亲电的α，β-不饱和羰基，可以与谷胱甘肽(GSH)等亲核化合物反应，但GSH-姜黄素偶联物的形成尚未被证实。在本研究中，我们研究了姜黄素与谷胱甘肽的反应以及重组人谷胱甘肽S转移酶P1-1对反应动力学的影响。FAB-MS和MALDI-MS鉴定的姜黄素谷胱甘肽基化产物包括姜黄素的单-和双-谷硫基加合物以及阿魏酸甲基酮(FMK)和阿魏醛(FAL)的GSH加合物的环重排产物。在10 mM磷酸二氢钾、pH 7.0和1 mM GSH中，GSTP1-1的存在显著加快了GSH介导的姜黄素的初始消耗速度。用高效液相色谱法测定GSTP1-1的动力学表明，底物抑制(姜黄素的表观K-m为25+/-11 mU，姜黄素的表观K-I为8+/-3 mU)。GSTP1-1还催化FMK和FAL的GSH加合物生成姜黄素的反向反应。(C)2000由爱思唯尔科学爱尔兰有限公司出版。保留所有权利。
Curcumin (diferuloylmethane), a yellow pigment of turmeric with antioxidant properties has been shown to be a cancer preventative in animal studies. It contains two electrophilic alpha, beta-unsaturated carbonyl groups, which can react with nucleophilic compounds such as glutathione (GSH), but formation of the GSH-curcumin conjugates has not previously been demonstrated. In the present studies, we investigated the reactions of curcumin with GSH and the effect of recombinant human glutathione S-transferase(GST)P1-1 on reaction kinetics. Glutathionylated products of curcumin identified by FAB-MS and MALDI-MS included mono- and di-glulathionyl-adducts of curcumin as well as cyclic rearrangement products of GSH adducts of feruloylmethylketone (FMK) and feruloylaldehyde (FAL). The presence of GSTP1-1 significantly accelerated the initial rate of GSH-mediated consumption of curcumin in 10 mM potassium phosphate, pH 7.0, and 1 mM GSH. GSTP1-1 kinetics determined using HPLC indicated substrate inhibition (apparent K-m for curcumin of 25 +/- 11 mu M, and apparent K-i for curcumin of 8 +/- 3 mu M). GSTP1-1 was also shown to catalyze the reverse reaction leading to the formation of curcumin from GSH adducts of FMK and FAL. (C) 2000 Published by Elsevier Science Ireland Ltd. All rights reserved.