Figure 1.

Transition metals and oxidative stress.A, transition metals. A section of the periodic table showing s-block (orange), d-block (cyan), and p-block (green) chemical elements. Transition metals of the first row, characterized by partially filled d-subshells, are shown in dark cyan squares in bolded black lettering. Zn (which possesses a complete d-subshell) is also shown in this group. The electronic structures of the d-block elements are shown in blue lettering. B, reactions of the superoxide anion; iron and redox cycling. Negatively charged free radical superoxide (O₂^•−, shown in red lettering) is the product of one-electron (e⁻) reduction of dioxygen (O₂). Upon protonation, O₂^•− can form the hydroperoxyl radical (HO₂^•). Superoxide dismutase (SOD, cyan oval) catalyzes the dismutation (disproportionation) of O₂^•−, thereby generating O₂ and hydrogen peroxide (H₂O₂). H₂O₂ is converted to H₂O by various antioxidant enzymes, such as catalases (CAT), glutathione peroxidases (GPX), and peroxiredoxins (PRX). Redox-active Fe²⁺ ions are oxidized by H₂O₂, generating highly reactive hydroxyl radicals (OH^•) and Fe³⁺ through the Fenton reaction. Fe³⁺ can be reduced to Fe²⁺ by O₂^•−, resulting in redox cycling (purple arrows). By itself, O₂^•− can reduce Fe³⁺ to Fe²⁺ within iron–sulfur cluster proteins, resulting in enzyme inactivation and accumulation of Fe²⁺, which further powers Fenton chemistry. Modified from Ref. (271).