
-   Glutathione S-transferase Mu (GSTM) gene family member, GSTM1, that play a key role in the detoxification of electrophilic compounds, such as cancer-causing toxins, anticarcinogens and products of oxidative stress via conjugating with glutathione [PMID: 15607001]. The catalytic activities of these GSTMs can repress pKa of the sulfhydryl group of reduced glutathione (GSH) when GSH is bound in the active site [PMID: 7817866]. The highly polymorphic, and allele mutations or genetic deletions of a certain base of GSTMs enhance the predisposition for multiple cancer, such as lung cancer [PMID: 18270371, PMID: 17900751, PMID: 22392686], colon cancer [PMID: 32776111, PMID: 36636093], cervical cancer [PMID: 22575983].

## Summary

The GSTM1 gene, encoding for the glutathione S-transferase Mu 1 protein, plays a pivotal role in detoxifying a range of electrophilic compounds, including environmental toxins, carcinogens, and oxidative stress products, by facilitating their conjugation with glutathione [CS: 9]. This process is crucial in the liver, an organ primarily responsible for detoxification [CS: 10]. When electrophilic compounds, such as those from drugs or environmental toxins, are present in the liver, they can cause cellular damage by interacting with cellular macromolecules like DNA, proteins, and lipids [CS: 9]. GSTM1's role is to mitigate this damage by catalyzing the conjugation of these harmful compounds with glutathione, rendering them more water-soluble and thus easier to excrete from the body [CS: 9]. This action not only protects cells from electrophile-induced damage but also helps maintain cellular redox balance, essential for normal cell function and survival [CS: 8].

In conditions where GSTM1 is dysregulated, particularly in its reduced expression or inactivity due to genetic polymorphisms or null mutations, the liver's capacity to detoxify these harmful electrophiles is significantly compromised [CS: 7]. This reduction in GSTM1 activity leads to an accumulation of electrophilic compounds and an increase in reactive oxygen species (ROS), which can cause oxidative stress and damage cellular components [CS: 7]. This damage can trigger a cascade of events that contribute to the development and progression of various liver diseases, including hepatocellular carcinoma, as indicated by the link between GSTM1 down-regulation and the ROS-TP53 axis disruption in hepatocellular carcinoma cells [CS: 6]. Hence, the dysfunction of GSTM1 directly impacts the liver's ability to counteract the toxic effects of electrophiles and oxidative stress, making it more susceptible to toxicity and disease progression [CS: 7].
