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Glutathione Transferases and Polymorphisms
Research Guide
What is Glutathione Transferases and Polymorphisms?
Glutathione transferases are a family of multifunctional enzymes that catalyze the conjugation of glutathione to electrophilic substrates, with genetic polymorphisms in their genes influencing oxidative stress response, disease susceptibility, cancer resistance, and drug metabolism.
The field encompasses 33,737 works on glutathione transferases, superoxide dismutase, and genetic polymorphisms in contexts such as oxidative stress, cancer resistance, and drug metabolism. "Glutathione S-Transferases" by Habig et al. (1974) purified homogeneous transferases B and C from rat liver and compared their kinetic and physical properties to transferases A and E. Research examines structural and functional characteristics of these antioxidant enzymes and their implications for therapeutic interventions targeting glutathione-related pathways.
Topic Hierarchy
Research Sub-Topics
GST Polymorphisms in Cancer Susceptibility
This sub-topic examines specific genetic polymorphisms in glutathione S-transferase (GST) genes and their association with increased or decreased risk of various cancers. Researchers investigate genotype-phenotype correlations, epidemiological data, and mechanistic roles in detoxification of carcinogens.
Glutathione S-Transferase Enzyme Structure
This area focuses on the crystallographic structures, active sites, and conformational dynamics of GST isoforms using X-ray crystallography and computational modeling. Studies explore substrate binding, isoform-specific functions, and evolutionary conservation.
Superoxide Dismutase Polymorphisms Oxidative Stress
Researchers study genetic variants in superoxide dismutase (SOD) genes and their impact on reactive oxygen species scavenging and cellular oxidative stress responses. This includes functional assays, disease associations, and interactions with other antioxidants.
GST Role in Anticancer Drug Metabolism
This sub-topic investigates how GST enzymes conjugate and detoxify chemotherapeutic agents, contributing to multidrug resistance in tumors. Research covers kinetic studies, expression profiling in cancer cells, and pharmacogenomic implications.
Nrf2 Regulation of GST Expression
Studies explore the Nrf2-ARE pathway's transcriptional control of GST and other antioxidant genes under oxidative stress conditions. This includes promoter analysis, knockout models, and therapeutic activation of Nrf2.
Why It Matters
Glutathione transferases play key roles in detoxifying electrophilic compounds and mitigating oxidative stress, with polymorphisms affecting cancer susceptibility and drug response. Habig et al. (1974) detailed the purification of transferases B and C from rat liver, enabling studies on their contributions to drug metabolism and toxicology. Valko et al. (2006) linked free radicals, metals, and antioxidants to oxidative stress-induced cancer, highlighting how polymorphisms in these enzymes influence disease risk. Trachootham et al. (2009) explored ROS-mediated targeting of cancer cells, showing potential for therapies exploiting glutathione pathways, as seen in elevated citations of these works (e.g., 17,815 for Habig et al.). In drug metabolism, polymorphisms alter enzyme activity, impacting treatment efficacy in oxidative stress-related conditions.
Reading Guide
Where to Start
"Glutathione S-Transferases" by Habig et al. (1974) is the first paper to read, as it provides foundational purification and characterization of these enzymes from rat liver, establishing kinetic and physical properties essential for understanding their basic function.
Key Papers Explained
"Glutathione S-Transferases" by Habig et al. (1974) lays the enzymatic groundwork, which Valko et al. (2006) in "Free radicals and antioxidants in normal physiological functions and human disease" extends to physiological roles and disease contexts. Valko et al. (2006) in "Free radicals, metals and antioxidants in oxidative stress-induced cancer" builds further by linking these enzymes to cancer mechanisms. Trachootham et al. (2009) in "Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach?" applies this foundation to therapeutic strategies exploiting glutathione pathways.
Paper Timeline
Most-cited paper highlighted in red. Papers ordered chronologically.
Advanced Directions
Current research in the 33,737 works continues exploring polymorphisms' impact on oxidative stress and drug resistance, with emphasis on antioxidant enzymes' structural characteristics and therapeutic targeting of glutathione pathways, as no recent preprints or news alter these trajectories.
Papers at a Glance
| # | Paper | Year | Venue | Citations | Open Access |
|---|---|---|---|---|---|
| 1 | Glutathione S-Transferases | 1974 | Journal of Biological ... | 17.8K | ✓ |
| 2 | Free radicals and antioxidants in normal physiological functio... | 2006 | The International Jour... | 13.9K | ✕ |
| 3 | Free radicals, metals and antioxidants in oxidative stress-ind... | 2006 | Chemico-Biological Int... | 6.5K | ✕ |
| 4 | Targeting cancer cells by ROS-mediated mechanisms: a radical t... | 2009 | Nature Reviews Drug Di... | 5.2K | ✕ |
| 5 | Oxidative stress, inflammation, and cancer: How are they linked? | 2010 | Free Radical Biology a... | 5.1K | ✓ |
| 6 | [12] Assays of glutathione peroxidase | 1984 | Methods in enzymology ... | 4.9K | ✕ |
| 7 | Oxyl radicals, redox-sensitive signalling cascades and antioxi... | 2007 | Cellular Signalling | 4.8K | ✕ |
| 8 | Oxidative Stress and Antioxidant Defense | 2012 | World Allergy Organiza... | 4.8K | ✓ |
| 9 | Role of Nrf2 in Oxidative Stress and Toxicity | 2013 | The Annual Review of P... | 4.6K | ✕ |
| 10 | Determination of glutathione and glutathione disulfide using g... | 1980 | Analytical Biochemistry | 4.5K | ✕ |
Frequently Asked Questions
What are glutathione S-transferases?
Glutathione S-transferases are enzymes that catalyze the conjugation of glutathione to electrophilic substrates. Habig et al. (1974) purified homogeneous transferases B and C from rat liver and compared their properties to A and E. These enzymes aid in detoxification and oxidative stress response.
How do genetic polymorphisms affect glutathione transferases?
Genetic polymorphisms in glutathione transferase genes alter enzyme activity, influencing oxidative stress response and disease susceptibility. They impact cancer resistance and drug metabolism by varying antioxidant capacity. This cluster of 33,737 papers investigates these effects in cell signaling and toxicology.
What role do glutathione transferases play in cancer?
Glutathione transferases contribute to cancer resistance through detoxification of reactive species. Valko et al. (2006) connected free radicals and antioxidants to oxidative stress-induced cancer. Trachootham et al. (2009) proposed ROS-mediated mechanisms to target cancer cells via these pathways.
How are glutathione levels measured?
Griffith (1980) described determination of glutathione and glutathione disulfide using glutathione reductase and 2-vinylpyridine. This method supports studies on oxidative stress and enzyme function. It is widely used in assays for antioxidant status.
What is the link between oxidative stress and glutathione transferases?
Oxidative stress involves reactive oxygen species countered by glutathione transferases and other antioxidants. Valko et al. (2006) outlined free radicals in physiological functions and disease. Reuter et al. (2010) linked oxidative stress, inflammation, and cancer through these mechanisms.
Open Research Questions
- ? How do specific polymorphisms in glutathione transferase genes modulate drug metabolism efficiency in diverse populations?
- ? What structural variations in glutathione S-transferases influence their substrate specificity under oxidative stress?
- ? In what ways do interactions between glutathione transferases and superoxide dismutase polymorphisms affect cancer susceptibility?
- ? How can glutathione transferase pathways be precisely targeted to overcome drug resistance in oxidative stress-related diseases?
- ? What are the functional consequences of glutathione transferase polymorphisms on cell signaling cascades?
Recent Trends
The field maintains 33,737 works with a focus on glutathione transferases' roles in oxidative stress and polymorphisms, as evidenced by sustained high citations for foundational papers like "Glutathione S-Transferases" by Habig et al. at 17,815 citations.
1974No recent preprints or news in the last 12 months indicate steady progression without new disruptions.
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