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Glutathione Peroxidase 4

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Selenium

Abstract

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 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 specific protein thiols when GSH is permissively low. This reaction accounts for midpiece stability and chromatin compaction in spermatozoa.

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Author information

Authors and Affiliations

  1. Department of Molecular Medicine, University of Padova, Viale G. Colombo 3, 35121, Padova, Italy

    Matilde Maiorino, Valentina Bosello-Travain, Giorgio Cozza, Giovanni Miotto, Antonella Roveri, Stefano Toppo, Mattia Zaccarin & Fulvio Ursini

  2. Department of Chemical Sciences, University of Padova, Via Marzolo, 1, 35121, Padova, Italy

    Laura Orian

Authors
  1. Matilde Maiorino
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  2. Valentina Bosello-Travain
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  3. Giorgio Cozza
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  4. Giovanni Miotto
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  5. Laura Orian
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  6. Antonella Roveri
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  7. Stefano Toppo
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  8. Mattia Zaccarin
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  9. Fulvio Ursini
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Corresponding author

Correspondence to Matilde Maiorino .

Editor information

Editors and Affiliations

  1. Mouse Cancer Genetics Program, National Institutes of Health, National Cancer Institute, Bethesda, Maryland, USA

    Dolph L. Hatfield

  2. Institut für Biochemie und Molekularbiologie, Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Nordrhein-Westfalen, Germany

    Ulrich Schweizer

  3. Department of Biological Sciences, Towson University, Towson, Maryland, USA

    Petra A. Tsuji

  4. Division of Genetics, Department of Medicine, Brigham and Women’s Hospital Harvard Medical School, Boston, Massachusetts, USA

    Vadim N. Gladyshev

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Maiorino, M. et al. (2016). Glutathione Peroxidase 4. In: Hatfield, D., Schweizer, U., Tsuji, P., Gladyshev, V. (eds) Selenium. Springer, Cham. https://doi.org/10.1007/978-3-319-41283-2_18

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