ABSTRACT
Peroxides are chemical compounds in which two oxygen atoms are linked together by a single covalent bond. Hydrogen peroxide (H2O2), the simplest peroxide, is formed through different routes in biological systems: (1) superoxide radical (O2 • −) dismutation, which can be spontaneous, or, depending on the organism and cellular compartment, catalyzed by different superoxide dismutases (SODs) [1–3]; (2) one-electron O2 • − reduction, such as during aconitase oxidation [4,5]; or (3) direct two-electron reduction of oxygen, which can be catalyzed by the divalent 50activity of several oxidases, including xanthine oxidase, Ero1, aldehyde oxidase, and monoamine oxidase [6–10] (Figure 3.1). In turn, peroxynitrous acid (ONOOH)* is a peroxy acid (or peracid), that is, a compound that contains an acidic –OOH group. ONOOH is the conjugated acid of peroxynitrite anion (ONOO−) (pK a = 6.6–6.8 [11–13]), whose main biological source is the rapid recombination reaction between O2 • − and nitric oxide (•NO) radicals [14–16]† (Figure 3.1). •NO is a small and lipophilic radical that can diffuse through membranes [20,21]. On the contrary, the charged nature of O2 • − (the pK a of the conjugated acid hydroperoxyl radical (HO2 •) is 4.8 [22]) limits its diffusion through membranes to those expressing anion channels, or to those delimiting compartments with acidic pH that allow O2 • − protonation at a significant proportion [23]. Moreover, the diffusion distance for O2 • − is estimated to be very short (~ 0.5 μm) [24]. Thus, ONOOH as well as H2O2 arising from O2 • − are expected to be formed primary at the main sites of O2 • − generation. Depending on the cell type, those sites could be mitochondria, phagosomes of inflammatory cells, as well as the extracellular space. Additionally, O2 • − can be formed through redox-cycling of xenobiotics at different cell compartments [25].
