Glutathione S-transferase (GST) is a protein that helps reduce oxidative stress in cells. Part of this function is mediated by eliminating partially metabolized drugs and natural toxic compounds in organisms. In addition, it has roles in the synthesis of steroids and some other complex regulatory compounds in mammalian cells. There are a number of different types of GST localized to different cellular compartments, forming a large enzyme family. They catalyze the transfer of glutathione to reduce an oxidized compound.
The classic role for glutathione S-transferase is in the conjugation of foreign compounds, known as xenobiotics. Such compounds can range from prescription drugs to toxins that humans have encountered in their diets to pesticides and environmental pollutants. Plants contain a number of toxic compounds, while fungi sometimes contaminate food stocks and produce mycotoxins. If such compounds are lipophilic, or tending to dissolve in membranes, they are usually detoxified by a two-phase system in the liver’s membranes.
Phase I of detoxification frequently involves cytochrome P450 enzymes, which introduce one oxygen molecule from the air into the compound being detoxified. Glutathione S-transferases can carry out Phase II detoxification by conjugating the –OH group. This involves the transfer of glutathione to the oxygen moiety. The formation of the modified group generally makes the compounds more soluble in water, and they can be excreted from the body in the urine. Occasionally, these reactions make a compound more carcinogenic.
Reactive oxygen species (ROS), such as peroxides and free radicals, contribute to oxidative stress in cells. This can damage membranes, proteins, and DNA — contributing to tissue damage. The presence of an excess of these compounds has been linked with accelerated aging. Glutathione S-transferase can help to neutralize these molecules and acts as a cellular antioxidant.
Other types of glutathione S-transferase can also be involved in the synthesis of complex signaling molecules. For instance, they are involved in the biosynthesis of eicosanoids, a group of complex compounds including the signaling molecules leukotrienes and prostagladin. Additionally, this type of enzyme is partly involved in the biosynthesis of the hormones testosterone and progesterone.
There are a large number of different forms of glutathione S-transferase. Some are found in the cytosol, while others are microsomal or mitochondrial. They are found in animals, plants, and bacteria. Glutathione S-transferases have a number of different families, with many containing multiple members per family. The presence of such a super-family enables the enzymes to have a wide array of specialized functions.
