Interplay of carbon dioxide and peroxide metabolism in mammalian cells.

The carbon dioxide/bicarbonate (CO/HCO) molecular pair is ubiquitous in mammalian cells and tissues, mainly as a result of oxidative decarboxylation reactions that occur during intermediary metabolism. CO is in rapid equilibrium with HCOvia the hydration reaction catalyzed by carbonic anhydrases. Far from being an inert compound in redox biology, CO enhances or redirects the reactivity of peroxides, modulating the velocity, extent, and type of one- and two-electron oxidation reactions mediated by hydrogen peroxide (HO) and peroxynitrite (ONOO/ONOOH). Herein, we review the biochemical mechanisms by which CO engages in peroxide-dependent reactions, free radical production, redox signaling, and oxidative damage. First, we cover the metabolic formation of CO and its connection to peroxide formation and decomposition. Next, the reaction mechanisms, kinetics, and processes by which the CO/peroxide interplay modulates mammalian cell redox biology are scrutinized in-depth. Importantly, CO also regulates gene expression related to redox and nitric oxide metabolism and as such influences oxidative and inflammatory processes. Accumulated biochemical evidence in vitro, in cellula, and in vivo unambiguously show that the CO and peroxide metabolic pathways are intertwined and together participate in key redox events in mammalian cells.