FIG. 3.

ROS and RNS relevant to NAFLD and hepatic IR. Superoxide anion (O₂^•−) is formed in the one-electron reduction of O₂ by CYP enzymes or the ETC. Thereafter, different SODs catalyze the dismutation of O₂^•− into hydrogen peroxide (H₂O₂). In addition, H₂O₂ is formed in the two-electron reduction of O₂ by AOX, CYP enzymes, or ERO1. H₂O₂ can react with transition metals such as ferrous iron (Fe²⁺, green arrows) to form hydroxyl radical (•OH). Alternatively, O₂^•− reacts with NOS-derived nitric oxide (•NO) to form peroxynitrite anion (ONOO⁻), which exists in equilibrium with its conjugate acid peroxynitrous acid (ONOOH, pK_a=6.8). Both forms of peroxynitrite can react with Fe²⁺ to generate nitrogen dioxide (•NO₂). •NO₂ is also formed during the homolytic fission of ONOOH, along with •OH, as well as in the reaction between ONOO^- and CO₂, also yielding carbonate radical anion (CO₃^•−). The free radicals •OH, •NO₂, and CO₃^•− are indicated in red to emphasize their high reactivity, which enables them to irreversibly alter the chemical structure of biomolecules (light gray arrow) as described in section “Molecular targets of ROS/RNS in NAFLD and IR.” AOX, fatty acyl-CoA oxidase; ERO1, ER oxidoreductin 1; ETC, electron transport chain; IR, ischemia-reperfusion; NOS, nitric oxide synthase; SOD, superoxide dismutase. To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/ars