Figure 8.

H₂O₂ readily diffuses through the cell membrane. High concentrations overwhelm catalase and peroxidase enzymes leading to hydroxyl radical formation via Fenton reaction. In addition, high concentration of H₂O₂ can inhibit superoxide dismutase (SOD) driving Haber-Weiss reaction and additional production of hydroxyl radical. These ROS (hydroxyl radical and superoxide radical) cause toxicity through lipid peroxidation, nucleic acid damage and protein oxidation. Zn²⁺ ions require cell membrane transporters to enter the cell. In high concentrations that exceed normal homeostatic mechanism these ions displace other metal ions cofactors on proteins, causing mis-metallation and resulting protein dysfunction. Evidence here suggests an alternative mechanism for ZnO-NPs. ZnO-NPs result in dramatic increases in pyrimidine biosynthesis, sugar metabolism and decreases in amino acid synthesis. This combination or cellular processes suggests that ZnO-NPs alter energy metabolism within the cell. The precise mechanism by which ZnO-NPs enter the cell and the specific intracellular molecular targets remain unclear.