The roles and interrelationship of the three redox-inert ions of magnesium, calcium, and zinc in redox biochemistry

The divalent cations of magnesium (Mg 2+ ), calcium (Ca 2+ ), and zinc (Zn 2+ ) are major determinants of the structure and function of proteins and nucleic acids. They complement each other as signaling ions and are critically important components for controlling virtually all systemic and cellular functions. Though redox-inert in biology, i.e., not undergoing redox chemistry, they nevertheless affect redox metabolism, redox signaling and the control of reactive species in multiple and interdependent ways. Considering magnesium and zinc as antioxidants is neither chemically correct nor is it a unique description of their biological activities which depend on their concentrations. While calcium and magnesium have only indirect roles in redox biology, zinc coordination environments have both direct and indirect roles. The reason for zinc’s direct role is that the sulfur donor atom from cysteine as a ligand confers redox activity on zinc sites. It makes cellular zinc distribution dependent on redox potentials. It establishes a redox switch that converts redox signals into zinc ion signals or disrupts the functions of zinc proteins under oxidative stress. Redox biology affects the individual homeostatic systems that tightly and dynamically control each of these metal ions. Vice versa, metal deficiency as well as metal overload affect redox biology. The interactions of the three metal ions call for their ratios to be monitored in the diet and evaluated clinically. Implementing such screening has enormous implications for health as large percentages of the world’s population are deficient in magnesium or zinc.