Catabolism of glutathione conjugates in Arabidopsis thaliana -: Role in metabolic reactivation of the herbicide safener fenclorim
Catabolism of glutathione conjugates in Arabidopsis thaliana -: Role in metabolic reactivation of the herbicide safener fenclorim
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DOI：
10.1074/jbc.m801998200
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发表时间：
2008-07-25
影响因子：
4.8
通讯作者：
Edwards, Robert
中科院分区：
文献类型：
--
作者：
Brazier-Hicks, Melissa;Evans, Kathryn M.;Edwards, Robert
安全剂fenclorim（4，6-二氯-2-苯基嘧啶）通过增强解毒谷胱甘肽S-转移酶（GST）的表达来增加水稻对氯乙酰苯胺除草剂的耐受性。Fenclorim也提高了GST在拟南芥，而在悬浮培养中研究这种诱导的功能意义，我们确定，这些酶谷胱甘肽的安全。将所得S-（fenclorim）谷胱甘肽缀合物依次加工成S-（fenclorim）-γ-谷氨酰-半胱氨酸和S-（fenclorim）-半胱氨酸（FC），后者在细胞和培养基中积累。然后FC被分解代谢为4-氯-6-（甲硫基）-苯基嘧啶（CMTP）或用丙二酸进行N-酰化。这些半胱氨酸衍生物有不同的命运，与酶负责它们的形成被诱导fenclorim和FC。通过丙二酰辅酶A依赖性N-丙二酰转移酶的作用，由FC形成Fenclorim-N-丙二酰半胱氨酸。然后，一小部分的解草磷-N-丙二酰半胱氨酸进行脱羧，产生推定的S-解草磷-N-乙酰半胱氨酸中间体，其进行第二轮GST介导的S-谷胱甘肽化和随后的蛋白水解加工。CMTP的形成是由半胱氨酸共轭β-裂解酶和S-甲基转移酶的协同作用催化的，这两种活性受到协调调节。虽然测试的fenclorim缀合物在拟南芥中显示出很少的GST诱导活性，但CMTP的形成导致代谢再活化，产物显示出良好的增强活性。此外，CMTP还诱导了水稻中的GST和除草剂安全活性。生物活化的CMTP又与谷胱甘肽缀合并加工成丙二酰半胱氨酸衍生物。这些结果揭示了一组令人惊讶的复杂的竞争性分解代谢反应，这些反应作用于进入植物中S-谷胱甘肽化途径的外源性物质，这可能导致解毒和生物活化。
The safener fenclorim (4,6-dichloro-2-phenylpyrimidine) increases tolerance to chloroacetanilide herbicides in rice by enhancing the expression of detoxifying glutathione S-transferases (GSTs). Fenclorim also enhances GSTs in Arabidopsis thaliana, and while investigating the functional significance of this induction in suspension cultures, we determined that these enzymes glutathionylated the safener. The resulting S-(fenclorim)glutathione conjugate was sequentially processed to S-(fenclorim)-gamma-glutamyl-cysteine and S-(fenclorim)-cysteine (FC), the latter accumulating in both the cells and the medium. FC was then either catabolized to 4-chloro-6-(methylthio)-phenylpyrimidine (CMTP) or N-acylated with malonic acid. These cysteine derivatives had distinct fates, with the enzymes responsible for their formation being induced by fenclorim and FC. Fenclorim-N-malonylcysteine was formed from FC by the action of a malonyl-CoA-dependent N-malonyltransferase. A small proportion of the fenclorim-N-malonylcysteine then underwent decarboxylation to yield a putative S-fenclorim-Nacetylcysteine intermediate, which underwent a second round of GST-mediated S-glutathionylation and subsequent proteolytic processing. The formation of CMTP was catalyzed by the concerted action of a cysteine conjugate beta-lyase and an S-methyltransferase, with the two activities being coordinately regulated. Although the fenclorim conjugates tested showed little GST-inducing activity in Arabidopsis, the formation of CMTP resulted in metabolic reactivation, with the product showing good enhancing activity. In addition, CMTP induced GSTs and herbicide-safening activity in rice. The bioactivated CMTP was in turn glutathione-conjugated and processed to a malonyl cysteine derivative. These results reveal the surprisingly complex set of competing catabolic reactions acting on xenobiotics entering the S-glutathionylation pathway in plants, which can result in both detoxification and bioactivation.