Dept. of Biochemistry, Sri Venkateswara University, Tirupati, Andhra Pradesh, India.
Dept. of Biochemistry, Sri Venkateswara University, Tirupati, Andhra Pradesh, India.
Chem Biol Interact. 2018 Oct 1;294:81-90. doi: 10.1016/j.cbi.2018.08.023. Epub 2018 Aug 23.
Glutathione S-transferases (GSTs), the versatile phase II biotransformation enzymes, metabolize and detoxify a wide variety of toxic chemical compounds like carcinogens, chemotherapeutic drugs, environmental pollutants and oxidative stress products. GSTs are currently of great interest in drug discovery, nanotechnology and biotechnology because of their involvement in many major cellular processes. GSTs, which are either homo or hetero dimeric proteins mediate catalytic binding between glutathione (GSH) and an array of either endogenous or exogenous toxic compounds to form a highly soluble detoxified complex which is then eliminated. Polycyclic aromatic hydrocarbons (PAHs) which are composed of two or more benzene rings bonded as linear, cluster or angular arrangements are used as intermediaries in pharmaceuticals, agricultural products, photographic products, thermosetting plastics, lubricating materials and other chemical products. Foods those cooked at high temperatures by grilling, roasting, frying and smoking are the main sources for the persistent bio-accumulation of PAHs in food chain. The carcinogenic, mutagenic and immunosuppressive effects of PAHs are well established. A well-known polycyclic aromatic hydrocarbon, methylcholanthrene is a potential carcinogenic, neurotoxic, mutagenic and tumour causing agent that is used as an experimental carcinogen in biological research. Methylcholanthrene converts into reactive metabolites when it enters living cells and those reactive metabolites oxidize DNA, RNA, proteins and lipids and form DNA and protein adducts as well. GSTs play major role in the detoxification of reactive metabolites of methylcholanthrene by mediating catalytic binding with GSH to form a highly soluble detoxified complex which is then eliminated. This review summarizes the role of GSTs in the detoxification of a polycyclic aromatic hydrocarbon, methylcholanthrene.
谷胱甘肽 S-转移酶（GSTs）是多功能的 II 相生物转化酶，可代谢和解毒多种有毒化学化合物，如致癌物、化疗药物、环境污染物和氧化应激产物。由于 GSTs 参与许多主要的细胞过程，因此它们在药物发现、纳米技术和生物技术中引起了极大的关注。GSTs 是同或异二聚体蛋白，介导谷胱甘肽（GSH）与一系列内源性或外源性有毒化合物之间的催化结合，形成高度可溶性的解毒复合物，然后将其消除。多环芳烃（PAHs）由两个或多个苯环以线性、簇或角状排列组成，用作制药、农产品、摄影产品、热固性塑料、润滑材料和其他化学产品的中间体。在高温下烤制、烘烤、油炸和烟熏的食物是多环芳烃在食物链中持久生物积累的主要来源。多环芳烃的致癌、致突变和免疫抑制作用已得到充分证实。一种著名的多环芳烃甲基胆蒽是一种潜在的致癌、神经毒性、致突变和肿瘤形成剂，被用作生物研究中的实验性致癌剂。当甲基胆蒽进入活细胞时，会转化为反应性代谢物，这些反应性代谢物氧化 DNA、RNA、蛋白质和脂质，并形成 DNA 和蛋白质加合物。GSTs 通过与 GSH 进行催化结合，在甲基胆蒽的反应性代谢物解毒中发挥主要作用，形成高度可溶性的解毒复合物，然后将其消除。这篇综述总结了 GSTs 在多环芳烃甲基胆蒽解毒中的作用。
