Chapter 18. 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, Km and Vmax are infinite. 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 peculiar 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 specific protein thiols when GSH is permissively low. This reaction accounts for midpiece stability and chromatin compaction in spermatozoa.

Glutathione peroxidase 4, pp 223-234. In Selenium. Its Molecular Biology and Role in Human Health. 4th ed.

MAIORINO, MATILDE;BOSELLO TRAVAIN, VALENTINA;COZZA, GIORGIO;MIOTTO, GIOVANNI;ORIAN, LAURA;ROVERI, ANTONELLA;TOPPO, STEFANO;ZACCARIN, MATTIA;URSINI, FULVIO
2016

Abstract

Chapter 18. 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, Km and Vmax are infinite. 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 peculiar 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 specific protein thiols when GSH is permissively low. This reaction accounts for midpiece stability and chromatin compaction in spermatozoa.
2016
Selenium. Its Molecular Biology and Role in Human Health, 4th ed.
978-3-319-41283-2
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11577/3199044
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