, Volume 22, Issue 1, pp 149–157 | Cite as

Molecular aspects of human cellular zinc homeostasis: redox control of zinc potentials and zinc signals

  • Wolfgang MaretEmail author


Zinc(II) ions are essential for all forms of life. In humans, they have catalytic and structural functions in an estimated 3,000 zinc proteins. In addition, they interact with proteins transiently when they regulate proteins or when proteins regulate cellular zinc re-distribution. As yet, these types of zinc proteins have been explored poorly. Therefore the number of zinc/protein interactions is potentially larger than that given by the above estimate. Confronted with such a wide range of functions, which affect virtually all aspects of cellular physiology, investigators have begun to elucidate the molecular mechanisms of cellular homeostatic control of zinc, especially the functions of transporter, sensor, and trafficking proteins, such as metallothioneins, in providing the correct amounts of zinc ions for the synthesis of zinc metalloproteins. The sulfur-containing amino acid cysteine in proteins has an important role in the cellular mobility of zinc ions. Sulfur-coordination environments provide sufficiently strong interactions with zinc ions; they can undergo fast ligand-exchange; and they can serve as molecular redox switches for zinc binding and release. For the cellular functions of zinc, the free zinc ion concentrations (zinc potentials, pZn = −log[Zn2+]) and the zinc buffering capacity are critically important parameters that need to be defined quantitatively. In the cytoplasm, free zinc ions are kept at picomolar concentrations as a minute fraction of the few hundred micromolar concentrations of total cellular zinc. However, zinc ion concentrations can fluctuate under various conditions. Zinc ions released intracellularly from the zinc/thiolate clusters of metallothioneins or secreted from specialized organelles are potent effectors of proteins and are considered zinc signals. The cellular zinc buffering capacity determines the threshold between physiological and pathophysiological actions of zinc ions. When drugs, toxins, other transition metal ions or reactive compounds compromise zinc buffering, large zinc ion fluctuations can injure cells through effects on redox biology and interactions of zinc ions with proteins that are normally not targeted.


Zinc Redox biology Homeostatic control Metalloregulation Metallothionein 





Metal response element (MRE)-binding transcription factor-1



This work was supported by Grant GM 065388 from the National Institutes of Health, the John Sealy Memorial Endowment Fund, a pilot project grant from the UTMB Claude Pepper Older Americans Independence Center, and a sponsored research agreement with Neurobiotex Inc, Galveston, TX.


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© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  1. 1.Division of Human Nutrition, Department of Preventive Medicine and Community HealthThe University of Texas Medical BranchGalvestonUSA
  2. 2.Division of Human Nutrition, Department of AnesthesiologyThe University of Texas Medical BranchGalvestonUSA

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