Reference Number: 681
Year: 2023
Link: Link to original paper
Summary
Abstract
In humans, the cytosolic glutathione S-transferase (GST) family of proteins is encoded by 16 genes presented in seven different classes. GSTs exhibit remarkable structural similarity with some overlapping functionalities. As a primary function, GSTs play a putative role in Phase II metabolism by protecting living cells against a wide variety of toxic molecules by conjugating them with the tripeptide glutathione. This conjugation reaction is extended to forming redox sensitive post-translational modifications on proteins: S-glutathionylation. Apart from these catalytic functions, specific GSTs are involved in the regulation of stress-induced signaling pathways that govern cell proliferation and apoptosis. Recently, studies on the effects of GST genetic polymorphisms on COVID-19 disease development revealed that the individuals with higher numbers of risk-associated genotypes showed higher risk of COVID-19 prevalence and severity. Furthermore, overexpression of GSTs in many tumors is frequently associated with drug resistance phenotypes. These functional properties make these proteins promising targets for therapeutics, and a number of GST inhibitors have progressed in clinical trials for the treatment of cancer and other diseases.
Summary of Findings
This review gives a useful overview of the uses of the GST gene / enzyme family. GSTs are a family of enzymes that help protect cells from damage by detoxifying harmful substances. They do this by attaching a molecule called glutathione (GSH) to toxic compounds, making them easier to remove from the body. GSTs are found in nearly all cells and come in different types, each with slightly different roles.
GSTP1 is one of the most studied GST enzymes, and it plays several important roles beyond detoxification:
1. Detoxification and Drug Resistance
- GSTP1 helps neutralize toxic chemicals, including drugs and pollutants.
- It is often overproduced in cancer cells, which can make tumors resistant to chemotherapy.
- For example, GSTP1 contributes to the breakdown of cisplatin, a cancer drug, in a way that can lead to kidney damage.
2. Protein Modification (S-Glutathionylation)
- GSTP1 can attach glutathione to specific proteins, modifying their function.
- This process helps regulate how cells respond to stress and maintain balance.
- One key target is peroxiredoxin VI (Prdx VI), an antioxidant enzyme. GSTP1 helps restore its activity after it has been damaged by oxidative stress.
- Different SNPs on GSTP1 affect how well it performs this role, which may influence how people respond to stress or toxins.
3. Cell Signalling and Stress Response
- GSTP1 acts like a “bodyguard” for certain signalling proteins, especially JNK (a stress-activated kinase).
- Under normal conditions, GSTP1 binds to JNK and keeps it inactive.
- When cells are stressed, GSTP1 lets go of JNK, allowing it to activate and trigger responses like cell death or repair.
- GSTP1 also interacts with other signalling proteins like TRAF2 and NF-xB, helping to control inflammation and cell survival.
4. Impact on COVID-19 Susceptibility
- Genetic differences in GSTP1 and other GSTs may influence how people respond to COVID-19.
- Some SNPs are linked to higher or lower risk of infection and severity.
- For example, certain GSTP1 SNPs appear to reduce the likelihood of developing severe COVID-19 symptoms.
The authors suggest that this matters because GSTP1 is more than just a detox enzyme, it is a multitasker involved in:
- Protecting cells from oxidative damage
- Regulating stress and immune responses
- Influencing how people respond to drugs and infections
Because of its wide ranging roles, GSTP1 is being studied as a potential target for new therapies, especially in cancer and inflammatory diseases.
Significance for the Baker
A sourdough baker could use this GST and glutathione knowledge to design breads that naturally support antioxidant capacity and stress response pathways through ingredient choice and fermentation technique. Because glutathione levels rise during long, slow sourdough fermentation (especially because of the Lactobacillus sanfranciscensis) you can deliberately extend fermentation times or maintain a starter rich in these strains to maximise natural glutathione production. You can also tailor flour blends and inclusions to boost the amino acids needed for glutathione synthesis: whole grains and oats for glutamate and glycine, and seeds such as pumpkin or sunflower for cysteine precursors. Vegetable ferments or koji based ferments such as miso could be incorporated to increase free amino acids and umami or by serving them with the bread. By adjusting fermentation, flour choice, and inclusions, you can create personalised loaves aimed at supporting oxidative stress resilience, inflammation modulation, or simply enhanced digestibility and flavour.
