ABSTRACT
Over-oxidation of catalytic cysteine to sulfinic acid in classic 2-Cys peroxiredoxins is reversible under reduction/reactivation by sulfiredoxin. An overoxidation of the peroxidatic Cys47 to sulfinic acid in peroxiredoxin VI (Prdx6) is irreversible and results in permanent inactivation of Prdx6 as a peroxidase. The biological significance of Prdx6 is defined by its unique antioxidant protection of the structural and functional integrity of cellular membranes. The manifestation of the oxidative damage to the biological membranes is lipid peroxidation (LP). LP is a radical chain reaction which occurs in a phospholipid bilayer under oxidative stress. It affects the unsaturated acyl chains of phospholipids through a production of hydroperoxyl groups. The catalytic cycle of Prdx6 requires two molecules of Glutathione (GSH) and thus resembles the catalytic cycle of classic glutathione peroxidases. An alteration of Prdx6 expression in the brains of "positive limb of the circadian clock"-compromised mice might indicate its involvement in the neuronal redox homeostasis and prevention of neurodegeneration.
