Figure 2.

Main cellular ROS and antioxidant mechanisms. Superoxide anion radical (O₂^•–) is the primary ROS produced by various physiological and pathophysiological processes. Reduction of O₂^•– by SODs or ascorbate (Asc) produces a less reactive but more diffusible H₂O₂ which is detoxified by catalase, peroxiredoxin 1 (PRDX1), and glutathione peroxidase 1 (GPX1). Reaction of H₂O₂ with free Fe(II) and less frequently Cu(I) yields a highly damaging ^•OH radical. Hydroxyl and other reactive radicals are also formed during the decomposition of peroxynitrite generated in the reaction of nitric oxide radical (^•NO) with O₂^•–. In comparison with the biological processes, ascorbate makes no significant contribution to the detoxification of H₂O₂ and plays a minor role in the removal of cytoplasmic O₂^•– in the majority of cells. Secondary radicals (tertiary ROS) arising from H₂O₂ and ONOO^– lack specialized enzymatic defenses and are primarily detoxified by small antioxidants such as ascorbate and small thiols (glutathione). Cells also lack enzymatic processes for removal of singlet oxygen (¹O₂) which is effectively eliminated by ascorbate via a two-electron reduction to H₂O₂. In contrast to the cytoplasm, the nucleus has a minimal or no SOD activity, which elevates the importance of ascorbate in scavenging superoxide in this cellular compartment.