Gpx4 Protein Glutathione Peroxidase 4 is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
Gpx4 Protein Glutathione Peroxidase 4 is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
<div class="infobox infobox-protein"> [@selenoproteins]
<table> [@ferroptosis]
<tr><th colspan="2" style="background:#f0f0f0;">Glutathione Peroxidase 4 (GPX4)</th></tr> [@lipid]
<tr><td><b>Protein Name</b></td><td>Glutathione Peroxidase 4 (GPX4)</td></tr>
<tr><td><b>Gene</b></td><td><a href="/genes/gpx4">GPX4</a></td></tr>
<tr><td><b>UniProt ID</b></td><td><a href="https://www.uniprot.org/uniprot/P36969">P36969</a></td></tr>
<tr><td><b>Alternative Names</b></td><td>Phospholipid Hydroperoxide GPX, PHGPx</td></tr>
<tr><td><b>Molecular Weight</b></td><td>~19 kDa (monomer)</td></tr>
<tr><td><b>Subcellular Localization</b></td><td>Cytosol, mitochondria, nucleus</td></tr>
<tr><td><b>Protein Family</b></td><td>Glutathione peroxidase family (Selenoprotein)</td></tr>
<tr><td><b>Structure</b></td><td>Tetramer of identical subunits</td></tr>
<tr><td><b>Catalytic Residue</b></td><td>Selenocysteine (Sec/U)</td></tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">ALZHEIMER</a>, <a href="/wiki/alzheimer's-disease" style="color:#ef9a9a">ALZHEIMER'S DISEASE</a>, <a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1277 edges</a></td>
</tr>
</table>
</div>
Glutathione Peroxidase 4 (GPX4) is a unique member of the glutathione peroxidase family that catalyzes the reduction of lipid hydroperoxides to their corresponding alcohols. Unlike other GPX enzymes that primarily reduce hydrogen peroxide and simple organic hydroperoxides, GPX4 directly reduces phospholipid and cholesterol hydroperoxides within cellular membranes, making it the central enzyme preventing ferroptosis.
The selenocysteine at position 47 (Sec^47) is essential for catalytic activity:
GPX4 catalyzes the reduction of lipid hydroperoxides:
GPX4 reduces various lipid peroxides:
By reducing lipid peroxides, GPX4:
| Compound | Mechanism | Stage | Notes |
|----------|-----------|-------|-------|
| Ferrostatin-1 | Lipid [ROS](/entities/reactive-oxygen-species) scavenger | Research | Prototype ferroptosis inhibitor |
| Liproxstatin-1 | GPX4 pathway stabilizer | Research | In vivo active |
| SRS | Small molecule activators | Discovery | Novel chemotypes |
| Strategy | Approach | Status |
|----------|----------|--------|
| Selenium supplementation | Increase Sec incorporation | Clinical trials |
| GSH precursors | NAC, NACET | Clinical |
| Iron chelation | Deferoxamine, Deferasirox | Approved |
| Vitamin E | Tocopherol supplementation | Supplements |
| Partner | Interaction Type | Function |
|---------|-----------------|----------|
| GSH | Substrate | Electron donor |
| GSR | Regeneration | GSSG reductase |
| SELENOP | Co-regulation | Selenoprotein synthesis |
| SLC7A11 | Metabolic link | Cystine/GSH axis |
GPX4 has multiple isoforms from alternative splicing:
The study of Gpx4 Protein Glutathione Peroxidase 4 has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
Interactive diagram showing GPX4's key relationships in the SciDEX knowledge graph (15 connections shown).