Maret W
Center for Biochemical and Biophysical Sciences and Medicine, Harvard Medical School, Boston, MA 02115, USA.
J Nutr. 2000 May;130(5S Suppl):1455S-8S. doi: 10.1093/jn/130.5.1455S.
A chemical and biochemical mechanism of action of the metallothionein (MT)/thionein (T) couple has been proposed. The mechanism emphasizes the importance of zinc/sulfur cluster bonding in MT and the significance of the two cluster networks as redox units that confer mobility on otherwise tightly bound and redox-inert zinc in MT. In this article, it is further explored how this redox mechanism controls the metabolically active cellular zinc pool. The low redox potential of the sulfur donor atoms in the clusters readily allows oxidation by mild cellular oxidants with concomitant release of zinc. Such a release by oxidants and the preservation of zinc binding by antioxidants place MT under the control of the cellular redox state and, consequently, energy metabolism. The binding of effectors, e.g., ATP, elicits conformational changes and alters zinc binding in MT. The glutathione/glutathione disulfide redox couple as well as selenium compounds effect zinc delivery from MT to the apoforms of zinc enzymes. This novel action of selenium on zinc/sulfur coordination sites has significant implications for the interaction between these essential elements. Tight binding and kinetic lability, modulation of MT by cellular ligands and the redox state, control of MT gene expression by zinc and many other inducers all support a critical function of the MT/T system in cellular homeostasis and distribution of zinc.
已经提出了金属硫蛋白（MT）/硫蛋白（T）对的化学和生化作用机制。该机制强调了MT中锌/硫簇键合的重要性以及两个簇网络作为氧化还原单元的意义，这些氧化还原单元赋予MT中原本紧密结合且氧化还原惰性的锌以流动性。在本文中，进一步探讨了这种氧化还原机制如何控制代谢活跃的细胞锌池。簇中硫供体原子的低氧化还原电位很容易被温和的细胞氧化剂氧化，同时释放锌。氧化剂的这种释放以及抗氧化剂对锌结合的保留使MT受细胞氧化还原状态的控制，进而受能量代谢的控制。效应物（如ATP）的结合会引发构象变化并改变MT中的锌结合。谷胱甘肽/谷胱甘肽二硫化物氧化还原对以及硒化合物会影响锌从MT向锌酶的脱辅基形式的传递。硒对锌/硫配位位点的这种新作用对这些必需元素之间的相互作用具有重要意义。紧密结合和动力学不稳定性、细胞配体和氧化还原状态对MT的调节、锌和许多其他诱导剂对MT基因表达的控制，都支持MT/T系统在细胞内锌稳态和分布中的关键作用。
