Inhibition of Na+/K+-ATPase and Mg2+-ATPase by metal ions and prevention and recovery of inhibited activities by chelators |
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Authors: | Danijela Krsti? Katarina Krinulovi? Vesna Vasi? |
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Institution: | 1. School of Medicine, University of Belgrade, Department of Chemistry, Vi?egradska, Belgrade, Serbia &2. Montenegro;3. Laboratory of Physical Chemistry, VIN?A Institute of Nuclear Sciences, Belgrade, Serbia & |
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Abstract: | Kinetics and inhibition of Na+/K+-ATPase and Mg2+-ATPase activity from rat synaptic plasma membrane (SPM), by separate and simultaneous exposure to transition (Cu2+, Zn2+, Fe2+ and.Co2+) and heavy metals (Hg2+and Pb2+) ions were studied. All investigated metals produced a larger maximum inhibition of Na+/K+-ATPase than Mg2+-ATPase activity. The free concentrations of the key species (inhibitor, MgATP2 ? , MeATP2 ? ) in the medium assay were calculated and discussed. Simultaneous exposure to the combinations Cu2+/Fe2+ or Hg2+/Pb2+caused additive inhibition, while Cu2+/Zn2+ or Fe2+/Zn2+ inhibited Na+/K+-ATPase activity synergistically (i.e., greater than the sum metal-induced inhibition assayed separately). Simultaneous exposure to Cu2+/Fe2+ or Cu2+/Zn2+ inhibited Mg2+-ATPase activity synergistically, while Hg2+/Pb2+ or Fe2+/Zn2+ induced antagonistic inhibition of this enzyme. Kinetic analysis showed that all investigated metals inhibited Na+/K+-ATPase activity by reducing the maximum velocities (Vmax) rather than the apparent affinity (Km) for substrate MgATP2-, implying the noncompetitive nature of the inhibition. The incomplete inhibition of Mg2+-ATPase activity by Zn2+, Fe2+ and Co2+ as well as kinetic analysis indicated two distinct Mg2+-ATPase subtypes activated in the presence of low and high MgATP2 ? concentration. EDTA, L-cysteine and gluthathione (GSH) prevented metal ion-induced inhibition of Na+/K+-ATPase with various potencies. Furthermore, these ligands also reversed Na+/K+-ATPase activity inhibited by transition metals in a concentration-dependent manner, but a recovery effect by any ligand on Hg2+-induced inhibition was not obtained. |
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Keywords: | Transition and heavy metals Na+/K+-ATPase Mg2+-ATPase kinetics inhibition |
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