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Why does GST make up 10% of the proteins in our cells? What's the story behind this?
Glutathione S-transferases (GSTs) are an important class of enzymes in organisms and are essential for detoxifying foreign substances. Studies have shown that GSTs make up up to 10% of the cytoplasmic protein composition in some mammalian organs, which has raised the question: why are these enzymes so important within cells?
GST family members can catalyze the binding of reduced glutathione (GSH) to exogenous substrates, thereby increasing their water solubility and promoting the excretion of toxicants.
GSTs belong to the second phase metabolic enzymes, which are mainly responsible for combining glutathione with toxic substances to achieve the effect of detoxification. These enzymes are divided into three major superfamilies: cytoplasmic, mitochondrial, and microsomal, and each family is further divided into multiple categories. The diversity of GSTs has resulted in a large number of sequences in public databases whose functions have not yet been clarified, meaning that there are potential functions that remain to be explored.
Functions and Roles of GST
The main function of GSTs is to catalyze the nucleophilic attack of GSH molecules on exogenous substrates, thereby preventing these compounds from interacting with key proteins and nucleic acids in cells. GSTs can increase the water solubility of toxins, which allows harmful substances to be successfully excreted from the body through transport proteins and reduce the oxidative stress of cells.GST not only binds substrates but also acts as a transporter, further assisting in cellular detoxification.
Diverse structures and classifications
From a structural point of view, the GST protein is globular, with an N-terminal mixed helical and β-strand domain and a fully helical C-terminal domain. Different GST classes differ in amino acid sequence, with cytoplasmic GSTs sharing more than 40% sequence homology, while other classes may share less than 25% homology. This structural diversity allows GST to exhibit remarkable flexibility in catalyzing different substrates.
GST and cancer associationGrowing evidence indicates the importance of GSTs, especially GSTP, in cancer development and chemoresistance. Studies have found that the expression level of GSTP in many cancer patients is significantly increased, and its role is not only in detoxification, but it is also likely related to the malignant transformation of tumor cells.
Many anticancer drugs are not good substrates for GSTP, which means that high expression of GSTP may promote the growth of tumor cells rather than just detoxification.
Clinical significance and application
In addition to their role in cancer development, GSTs are also implicated in a variety of diseases. GST polymorphisms contribute to susceptibility to many diseases such as asthma, atherosclerosis, and diabetes, making them potential therapeutic targets. In addition, GSTs can be used as biomarkers when cells are damaged to determine the extent of organ damage.
SCI pointed out that when cells are damaged, the amount of GST released will increase significantly. For example, the increase in α-GST in liver cells can serve as an indicator of liver damage. In cases of renal injury, urinary GST levels can also be used to quantify the extent of tubular damage.
Future Outlook
As scientists continue to study GST, they hope to further uncover its role in cell signaling and develop more effective treatments to combat a variety of diseases associated with oxidative stress. According to current scientific research, the role of GSTs in various physiological and pathological conditions is increasingly valued, which indicates that there may be more therapeutic opportunities in the future.
However, will the high expression of GST become a double-edged sword in cancer treatment?
