The function of zinc metallothionein: a link between cellular zinc and redox state.
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.
Maret
W
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Center for Biochemical and Biophysical Sciences and Medicine, Harvard Medical School, Boston, MA 02115, USA.
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D008668:Metallothionein / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D010084:Oxidation-Reduction / Q000187:drug effects; D012643:Selenium / Q000737:chemistry / Q000378:metabolism; D013455:Sulfur / Q000737:chemistry / Q000378:metabolism; D015032:Zinc / Q000378:metabolism / Q000502:physiology*
D000975:Antioxidants; C021267:zinc thionein; D013455:Sulfur; D000255:Adenosine Triphosphate; D008668:Metallothionein; D012643:Selenium; D015032:Zinc