Pathway Summary
The thioredoxin and glutathione/glutaredoxin systems help maintain the reduced environment of the cell and play a significant role in defending the cell against oxidative stress. They also have been proposed to play a role in the biosynthesis of purines and pyrimidines as required for DNA synthesis, protein folding and regulation, and sulfur metabolism Thioredoxins and glutaredoxins are small heat-stable proteins with redox-active cysteines that facilitate the reduction of other proteins by catalyzing cysteine thiol-disulfide exchange reactions Thioredoxins contain two conserved cysteines that exist in either a reduced form as in thioredoxin-(SH)2 or in an oxidized form as in thioredoxin-S2 when they form an intramolecular disulfide bridge Thioredoxins donate electrons from their active center dithiol to protein disulfide bonds (Protein-S2) that are then reduced to dithiols (Protein-(SH)2). The resulting oxidized thioredoxin disulfide is reduced directly by thioredoxin reductase with electrons donated by NADPH Hence the thioredoxin reduction system consists of thioredoxin, thioredoxin reductase, and NADPH. Oxidized glutaredoxins, on the other hand, are reduced by the tripeptide glutathione (gamma-Glu-Cys-Gly, known as GSH) using electrons donated by NADPH Hence the glutathioneglutaredoxin system consists of glutaredoxin, glutathione, glutathione reductase and NADPH. S. cerevisiae contains a cytoplasmic thioredoxin system comprised of the thioredoxins Trx1p and Trx2p and the thioredoxin reductase Trr1p, and a complete mitochondrial thioredoxin system comprised of the thioredoxin Trx3p and the thioredoxin reductase Trr2p Evidence suggests that the cytoplasmic thioredoxin system may have overlapping function with the glutathioneglutaredoxin system The mitochondrial thioredoxin system, on the other hand, does not appear to be able to substitute for either the cytoplasmic thioredoxin or glutathioneglutaredoxin systems Instead, the mitochondrial thioredoxn proteins, thioredoxin (Trx3p) and thioredoxin reductase (Trr2p) have been implicated in the defense against oxidative stress generated during respiratory metabolism The two cytoplasmic thioredoxins (Trx1p and Trx2p) are believed to supply reducing equivalents to the enzymes ribonucleotide reductase (Rnr1p, Rnr2p, Rnr3p, Rnr4p) and 3'-phosphoadenosine 5'-phosphosulfate (PAPS) reductase (Met16p) Deletion of either TRX1 or TRX2 has no effect on cell growth or morphology , but, deletion of both genes affects the cell cycle, and makes the cells auxotrophic for methioninecysteine Deletion of the single gene TRX2 does result in extreme sensitivity to H2O2 and is thereby believed to be involved in the response against H2O2 The expression of TRX2 and TRR1 are regulated by the transcription factors Yap1p and Skn7p in response to H2O2
Genes Involved
Genes whose products participate in this pathway, with their systematic names, EC numbers (where the gene product is an enzyme with an assigned EC number), and the gene's SGD description.
| Gene | Systematic Name | EC Number | Description |
|---|---|---|---|
| TRR1 | YDR353W | 1.8.1.9 | Cytoplasmic thioredoxin reductase |
| TRR2 | YHR106W | 1.8.1.9 | Mitochondrial thioredoxin reductase |
| TRX1 | YLR043C | Cytoplasmic thioredoxin isoenzyme | |
| TRX2 | YGR209C | Cytoplasmic thioredoxin isoenzyme | |
| TRX3 | YCR083W | Mitochondrial thioredoxin |
Functional Networks
Functional Networks show how the genes in this pathway work together: a graph linking the pathway to its genes and their shared GO biological-process terms and phenotype observables, and the GO-CAM causal activity models that involve these genes.
Shared Annotations
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GO-CAMs
GO-CAM (Gene Ontology Causal Activity Model) pathway models that involve the genes in this pathway. A gene can participate in more than one model, so use the dropdown to switch between them; the model for this pathway is shown by default.
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References
List of references used specifically to curate the information on this page.
- Grant CM (2001) Role of the glutathione/glutaredoxin and thioredoxin systems in yeast growth and response to stress conditions. Mol Microbiol 39(3):533-41 PMID: 11169096
- Holmgren A (1989) Thioredoxin and glutaredoxin systems. J Biol Chem 264(24):13963-6 PMID: 2668278
- Trotter EW and Grant CM (2005) Overlapping roles of the cytoplasmic and mitochondrial redox regulatory systems in the yeast Saccharomyces cerevisiae. Eukaryot Cell 4(2):392-400 PMID: 15701801
- Muller EG (1996) A glutathione reductase mutant of yeast accumulates high levels of oxidized glutathione and requires thioredoxin for growth. Mol Biol Cell 7(11):1805-13 PMID: 8930901
- Draculic T, et al. (2000) A single glutaredoxin or thioredoxin gene is essential for viability in the yeast Saccharomyces cerevisiae. Mol Microbiol 36(5):1167-74 PMID: 10844700
- Pedrajas JR, et al. (1999) Identification and functional characterization of a novel mitochondrial thioredoxin system in Saccharomyces cerevisiae. J Biol Chem 274(10):6366-73 PMID: 10037727
- Gonzalez Porqué P, et al. (1970) The involvement of the thioredoxin system in the reduction of methionine sulfoxide and sulfate. J Biol Chem 245(9):2371-4 PMID: 4392601
- Gonzalez Porqué P, et al. (1970) Purification of a thioredoxin system from yeast. J Biol Chem 245(9):2363-70 PMID: 5442277
- Muller EG (1991) Thioredoxin deficiency in yeast prolongs S phase and shortens the G1 interval of the cell cycle. J Biol Chem 266(14):9194-202 PMID: 2026619
- Muller EG (1994) Deoxyribonucleotides are maintained at normal levels in a yeast thioredoxin mutant defective in DNA synthesis. J Biol Chem 269(39):24466-71 PMID: 7929110
- Kuge S and Jones N (1994) YAP1 dependent activation of TRX2 is essential for the response of Saccharomyces cerevisiae to oxidative stress by hydroperoxides. EMBO J 13(3):655-64 PMID: 8313910
- Morgan BA, et al. (1997) The Skn7 response regulator controls gene expression in the oxidative stress response of the budding yeast Saccharomyces cerevisiae. EMBO J 16(5):1035-44 PMID: 9118942
Resources
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