Figure 1.

Formation of reactive oxygen species (ROS) in vascular cells. The reduction of oxygen (O₂) by one electron leads to the formation of superoxide anion (O₂^•−), which can be either dismutated to hydrogen peroxide (H₂O₂) spontaneously or in a reaction catalyzed by superoxide dismutase (SOD). Nitric oxide (NO•) is produced by endothelial nitric oxide synthase (eNOS) from L-arginine (L-Arg) and tetrahydrobiopterin. O₂^•− and NO• react spontaneously with each other to form peroxynitrite (ONOO⁻). H₂O₂ can also be generated directly from oxygen by some vascular oxidases, such as xanthine oxidase (XO), glucose oxidase (GO) and NOX4-containing NADPH-oxidases (NOX4). H₂O₂ can be scavenged by catalase (CAT) or glutathione peroxidase (GPx) to form water and oxygen or can undergo non-enzymatic reactions to generate the hydroxyl radical (OH•) in the metal-catalyzed Haber-Weiss or Fenton reaction. OH• may be protonated to the hydroperoxyl radical. Ferrous-containing enzymes, such as myeloperoxidase (MPO) are activated by H₂O₂ to form a highly reactive radical that can oxidize NO• to nitrogen dioxide anion (NO₂⁻) and react with NO₂⁻ to form nitrogen dioxide radical (NO₂•). NO₂• can, in turn, participate in nitrating events, such as the formation of nitrotyrosines (NO₂-Tyr). Alternatively, MPO can use H₂O₂ to form hypochlorous acid (HOCl). Singlet oxygen (1O₂) is formed upon the reaction of HOCl with H₂O₂.

Abbreviations: 1e⁻, one electron; 2e⁻, two electrons; BH₄, tetrahydrobiopterin; Cl⁻, chloride anion; Fe²⁺, ferrous iron; H⁺, hydrogen cation; Tyr, tyrosine.