Glutathione peroxidase 4

Glutathione peroxidase 4 (GPx4) is a selenocysteine (Sec)-containing glutathione peroxidase. GPx4 catalyzes the reduction of hydroperoxides and the oxidation of thiols through a ping-pong mechanism in which the redox transitions are faster than the formation of enzyme-substrate complexes; thus, K m and V max are infi nite. The formation of a charge separation in the redox center accounts for this extremely fast reaction. In the absence of reducing substrate, the oxidized selenium is stabilized, forming a bond with a nitrogen atom in the backbone. This reaction, which protects the enzyme from inactivation, is particular of Sec and does not take place when Cys substitutes for Sec. The glutathione (GSH)-dependent reduction of phospholipid hydroperoxides accounts for the vital function of GPx4 and links the peroxidase to a new subroutine of cell death, named ferroptosis. This reaction is also related to protection from cardio-metabolic disorders and promotion of viral spread and infectivity. Finally, GPx4 is also competent for the oxidation of specifi c protein thiols when GSH is permissively low. This reaction accounts for midpiece stability and chromatin compaction in spermatozoa.