Human Glutathione S-Transferases

Abstract

Human glutathione S-transferases (GSTs) are a functionally diverse family of soluble enzymes of detoxification that use reduced glutathione (GSH) in conjugation and reduction reactions. Toxic electrophiles, including a variety of carcinogens, are substrates for the GSTs and after conjugation or reduction they are more easily excreted into bile or urine. Many of the GSTs have been cloned, and the three-dimensional structures of GSTs from several species, including humans, have been determined. These data have provided significant insight into how the GSTs function as enzymes. Many GST substrates are inducers of GST gene expression; nonsubstrate inducers include H2O2 and other reactive oxygen species. The regulatory elements of several human GST genes have been partially characterized, and the regulation of the GSTs in humans appears to be very different from that in rodents. Several polymorphisms of GST expression occur commonly in humans and have been associated with an increased susceptibility to certain cancers, particularly when combined with other genetic and environmental factors such as smoking. The role of GSTs in protecting cells from injury by toxic electrophiles continues to be developed.

Relationship between glutathione S-transferase P1 polymorphisms and chronic obstructive pulmonary disease in a Tunisian population

“…The activity of this enzyme affected by substitution at position 105 changes the substrate-binding site architecture at the protein level, giving different kinetic properties to both allelic variants (Whalen and Boyer, 1998). As a consequence of such modification in genotypes is the incomplete catabolism of toxicants due to low enzymatic activity, which may lead to oxidative stress.…”

A Possible Relationship Between Polymorphisms of Glutathione S-Transferase M1, P1 and T1 Genes and Rheumatoid Arthritis in Zahedan, Southeast Iran

“…The most common substrates for GSTs are ROS compounds, which are products of oxidative stress (OS). [15] It is well known that individuals with the GSTM1 null or GSTT1 null genotypes display an absence of enzymatic activity and are thought to be at an elevated risk for the cytotoxic effects of a wide spectrum of carcinogens and xenobiotics. [16,17] In addition, it has been demonstrated that the GSTP1 Ile105Val polymorphism is associated with altered catalytic function and that GSTP1 malfunction makes cells vulnerable to oxidative DNA damage.…”

Lack of Any Association of GST Genetic Polymorphisms with Susceptibility to Ovarian Cancer - a Meta-analysis

“…A total of 10 published articles regarding the relationship between GSTs and ovarian cancer were identified by applying the inclusion criteria (Figure 1) (Sarhanis et al, 1996;Hengstler et al, 1998;Lallas et al, 2000;Baxter et al, 2001;Spurdle et al, 2001;Morari et al, 2006;Delort et al, 2008;Gates et al, 2008;Khokhrin et al, 2012;Oliveira et al, 2012), 10 articles documented GSTM1 (2578 cases and 3423 controls) (Sarhanis et al, DOI:http://dx.doi.org/10.7314/APJCP.2014.15.15.6131 GST Genetic Polymorphisms andSusceptibility to Ovarian Cancer 1996;Hengstler et al, 1998;Whalen et al, 1998;Lallas et al, 2000;Baxter et al, 2001;Clayton et al, 2001;Riman et al, 2002;Gates et al, 2008;Oliveira et al, 2012), 8 articles studied GSTT1 (2133 cases and 3141 controls) (Sarhanis et al, 1996;Hengstler et al, 1998;Spurdle et al, 2001;Morari et al, 2006;Gates et al, 2008;Khokhrin et al, 2012;Oliveira et al, 2012) and 5 articles reported GSTP1 rs1695 (641 cases and 1949 controls) (Spurdle et al, 2001;Morari et al, 2006;Delort et al, 2008;Khokhrin et al, 2012;Oliveira et al, 2012). More details of these studies were summarized in (Supplementary Table 1).…”

“…However, the majority of risk factors of OC are not clear, and the existing screening methods for OC such as serum CA 125, pelvic examination and transvaginal sonography (TVS) are not reliable in any risk group (Van Nagell et al, 1995;Bell et al, 1998;Jayde et al, 2012). The glutathione S-transferases (GSTs) enzymes are an important phase II isoenzyme group which can catalyze the conjugation of glutathione with a variety of electrophilic compounds (Whalen et al, 1998). Enzymes of the GST family in eukaryotic species are composed of multiple cytosolic and membrane-bound isoenzymes, among them GSTM1, GSTT1 and GSTP1 belong to human GSTs and have been proven to play an important role in human carcinogenesis.…”