GPX4
Glutathione Peroxidase 4 (GPX4) is a peroxidase enzyme, encoded for by the GPX4 gene which has a strong antioxidant activity. The main function of GPX4 is to detoxify hydrogen peroxide, produced by many reactions within a cell into water which can then be excreted. It can also detoxify lipid peroxides as well 1. As its name suggests GPX4 uses glutathione in order to detoxify hydrogen peroxide and other oxidative agents. Unlike other members of the GPX family, such as GPX1, GPX4 is able to use other antioxidants than glutathione and importantly is able to act within the cell membrane. As such it may act as a first line of defence, preventing oxidising agents from entering and damaging a cell 2,3.
Interestingly as with other GPX enzymes, GPX4 is one of the few proteins in humans which contain the non-standard amino acid selenocysteine, which replaces the standard cysteine. This replacement is thought to be a major contributor to the potent antioxidant activity of GPX4.
There is one SNP in the GPX4 gene which is associated with poor health outcomes, rs713041 or T660C.
| rsID Number | Major Allele | Minor Allele | Minor Allele Frequency (%) | Major Amino Acid | Minor Amino Acid |
|---|---|---|---|---|---|
| rs713041 | c | t | 40 | Leu | Leu |
Risk Description
Both the ‘C’ and ‘T’ alleles of T660C in the GPX4 gene carry an increased risk of various cancers, which is thought to be controlled by the their varying ability to incorporate selenium 4,5. It is not known if overall antioxidant capacity is altered by these changes, or if there is an observable difference between the two alleles.
Direct Nutrients:*
| Ingredient | Active Ingredient | Effect |
|---|---|---|
| Glutathione |
Glutathione is an important antioxidant in its own right, but is also used by GPX4 as a cofactor. In those carrying either the ‘T’ or ‘C’ allele of T660C which is associated with impaired antioxidant capacity supplementation with glutathione may improve outcomes. As the mechanism of impairment associated with T660 remains unknown it is not clear exactly how glutathione will benefit. |
|
Indirect Nutrients:*
| Ingredient | Active Ingredient | Effect |
|---|---|---|
| Selenium |
Two copies of the ‘C’ allele of T660C are associated with increased DNA damage when levels of selenium are low. However, when selenium levels are increased the rate of DNA damage decreases significantly 4,5. Therefore those carrying two copies of the ‘C’ allele of T660C may benefit from selenium supplementation. |
|
Nutritional Contraindications:*
| Ingredient | Active Ingredient | Effect |
|---|---|---|
| Selenium |
Those carrying the ‘T’ (including those carrying one C and one T) allele of T660C display reduced levels of DNA damage, which may correlate with cancer risk, compared to those carrying two copies of the ‘C’ allele when selenium levels are low. Whereas those with two copies of the ‘C’ allele respond positively to increasing levels of selenium, those carrying the ‘T’ allele show a mild increase in DNA damage 4,5. Therefore, those carrying the ‘T’ allele may wish to avoid additional selenium supplementation. |
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Discuss this information with your doctor before taking any course of action.
Citations:
- https://www.ncbi.nlm.nih.gov/pubmed/8039723
- https://www.ncbi.nlm.nih.gov/pubmed/12566075
- https://www.ncbi.nlm.nih.gov/gene/2879
- https://www.ncbi.nlm.nih.gov/pubmed/21459128
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3316745/