Oxidative stress and redox pathway (WP4466)

Mus musculus

This pathway represents biology relevant to glutathione, including biosynthesis, metabolism, redox cycle, uptake, glutathionylation and acivicin inhibition. Glutathione is an antioxidant that is synthesized in eukaryotes from L-cysteine, L-glutamic acid, and glycine in a two-step process involving gamma-glutamylcysteine synthetase and glutathione synthetase. Glutathione prevents cellular damage by acting as an electron donor to neutralize reactive oxygen species. Reactive glutathione is produced, which then reacts with another reactive glutathione molecule to produce glutathione disulfide, GSSG. It was based partly on [[Pathway:WP164 |WP164]] and [[Pathway:WP1770|WP1770]], with information added from literature. This pathway was created as a part of [https://www.nature.com/articles/s41590-020-0654-0 Mendiola et cl], pictured in fig 5.

Authors

Kristina Hanspers , Alex Pico , Egon Willighagen , Denise Slenter , Eric Weitz , and Lars Willighagen

Activity

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Cited In

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Organisms

Mus musculus

Communities

Annotations

Pathway Ontology

glutathione metabolic pathway glutathione biosynthetic pathway glutathione antioxidant pathway classic metabolic pathway

Participants

Label Type Compact URI Comment
GSH conjugates Metabolite kegg.compound:C02320
Glutamine Metabolite hmdb:HMDB0000641
Glutamate Metabolite hmdb:HMDB0000148
NADPH Metabolite hmdb:HMDB0000221
NADP+ Metabolite hmdb:HMDB0000217
Serine Metabolite hmdb:HMDB0000187
H2O Metabolite hmdb:HMDB0002111
H2O2 Metabolite hmdb:HMDB0003125
Cystine Metabolite hmdb:HMDB0000192
GSH Metabolite kegg.compound:C00051
Glutamyl amino acid Metabolite kegg.compound:C03740
Glycine Metabolite hmdb:HMDB0000123
Cysteine Metabolite kegg.compound:C00097
GSSG Metabolite cas:27025-41-8
acivicin Metabolite chebi:74545
O2 Metabolite chebi:15379
g-Glutamylcysteine Metabolite kegg.compound:C00669
5-Oxoproline Metabolite kegg.compound:C01879
Cysteine Metabolite hmdb:HMDB0000574
Homocysteine Metabolite hmdb:HMDB0000742
Amino acid Metabolite kegg.compound:C00151
Glutamylamino acid Metabolite kegg.compound:C03740
Cysteinyl-glycine Metabolite kegg.compound:C01419
O2- Metabolite chebi:18421
GTP Metabolite chebi:15996
Gpx5 GeneProduct ensembl:ENSMUSG00000004344
Prdx1 GeneProduct ensembl:ENSMUSG00000028691
Txn1 GeneProduct ensembl:ENSMUSG00000028367
Keap1 GeneProduct ensembl:ENSMUSG00000003308
Grxcr2 GeneProduct ensembl:ENSMUSG00000073574
Cd44 GeneProduct ensembl:ENSMUSG00000005087 CD44 interacts with and stabilizes XCT
Gss GeneProduct ensembl:ENSMUSG00000027610
Oplah GeneProduct ensembl:ENSMUSG00000022562
Slc1a2 GeneProduct ensembl:ENSMUSG00000005089
Slc7a11 GeneProduct ensembl:ENSMUSG00000027737 System Xc- is an antiporter that transports Cystine in and glutamate out. https://en.wikipedia.org/wiki/SLC7A11
Foxp3 GeneProduct ensembl:ENSMUSG00000039521
Gsto1 GeneProduct ensembl:ENSMUSG00000025068
Gstp1 GeneProduct ensembl:ENSMUSG00000060803
Gpx1 GeneProduct ensembl:ENSMUSG00000063856
Slc1a5 GeneProduct ensembl:ENSMUSG00000001918
Grxcr1 GeneProduct ensembl:ENSMUSG00000068082
Gpx4 GeneProduct ensembl:ENSMUSG00000075706
Gpx2 GeneProduct ensembl:ENSMUSG00000042808
G6pdx GeneProduct ensembl:ENSMUSG00000031400
Slc6a9 GeneProduct ensembl:ENSMUSG00000028542
Gclc GeneProduct ensembl:ENSMUSG00000032350
Nrf2 GeneProduct ensembl:ENSMUSG00000015839
Alox5 GeneProduct ensembl:ENSMUSG00000025701
Nrf1 GeneProduct ensembl:ENSMUSG00000058440
Gstt1 GeneProduct ensembl:ENSMUSG00000001663
Gsta1 GeneProduct ensembl:ENSMUSG00000074183
Gsr GeneProduct ensembl:ENSMUSG00000031584
Cbs GeneProduct ensembl:ENSMUSG00000024039
Idh1 GeneProduct ensembl:ENSMUSG00000025950
Mgst1 GeneProduct ensembl:ENSMUSG00000008540
Gstm2 GeneProduct ensembl:ENSMUSG00000040562
Gls GeneProduct ensembl:ENSMUSG00000026103
Gclm GeneProduct ensembl:ENSMUSG00000028124
Ggct GeneProduct ensembl:ENSMUSG00000002797
Gpx3 GeneProduct ensembl:ENSMUSG00000018339
Gpx6 GeneProduct ensembl:ENSMUSG00000004341
Gpx7 GeneProduct ensembl:ENSMUSG00000028597
Gpx8 GeneProduct ensembl:ENSMUSG00000021760
Idh2 GeneProduct ensembl:ENSMUSG00000030541
G6pd2 GeneProduct ensembl:ENSMUSG00000089992
Pgd GeneProduct ensembl:ENSMUSG00000028961
Gstt2 GeneProduct ensembl:ENSMUSG00000033318
Gstt3 GeneProduct ensembl:ENSMUSG00000001665
Gstm1 GeneProduct ensembl:ENSMUSG00000058135
Gstm3 GeneProduct ensembl:ENSMUSG00000004038
Gstm4 GeneProduct ensembl:ENSMUSG00000027890
Gstm5 GeneProduct ensembl:ENSMUSG00000004032
Gstm6 GeneProduct ensembl:ENSMUSG00000068762
Gstm7 GeneProduct ensembl:ENSMUSG00000004035
Gsta2 GeneProduct ensembl:ENSMUSG00000057933
Gsta3 GeneProduct ensembl:ENSMUSG00000025934
Gsta4 GeneProduct ensembl:ENSMUSG00000032348
Gstp2 GeneProduct ensembl:ENSMUSG00000038155
Gsto2 GeneProduct ensembl:ENSMUSG00000025069
Mgst2 GeneProduct ensembl:ENSMUSG00000074604
Mgst3 GeneProduct ensembl:ENSMUSG00000026688
Hpgds GeneProduct ensembl:ENSMUSG00000029919
Gstk1 GeneProduct ensembl:ENSMUSG00000029864
Ggt5 GeneProduct ensembl:ENSMUSG00000006344
Ggt6 GeneProduct ensembl:ENSMUSG00000040471
Ggt7 GeneProduct ensembl:ENSMUSG00000027603
Ggt1 GeneProduct ensembl:ENSMUSG00000006345 (5-L-Glutamyl)-L-amino acid
Abcc2 GeneProduct ensembl:ENSMUSG00000025194
Abcc5 GeneProduct ensembl:ENSMUSG00000022822
Lap3 GeneProduct ensembl:ENSMUSG00000039682
Anpep GeneProduct ensembl:ENSMUSG00000039062
Slc6a5 GeneProduct ensembl:ENSMUSG00000039728
Slco1a1 GeneProduct ensembl:ENSMUSG00000041698
Slco2a1 GeneProduct ensembl:ENSMUSG00000032548
Ctla4 GeneProduct ensembl:ENSMUSG00000026011
Cybb GeneProduct ensembl:ENSMUSG00000015340
Cyba GeneProduct ensembl:ENSMUSG00000006519
Rac1 GeneProduct ensembl:ENSMUSG00000001847
Ncf4 GeneProduct ensembl:ENSMUSG00000071715
Ncf1 GeneProduct ensembl:ENSMUSG00000015950
Ncf2 GeneProduct ensembl:ENSMUSG00000026480
Prdx2 GeneProduct ensembl:ENSMUSG00000005161
Prdx3 GeneProduct ensembl:ENSMUSG00000024997
Prdx4 GeneProduct ensembl:ENSMUSG00000025289
Prdx5 GeneProduct ensembl:ENSMUSG00000024953
Prdx6 GeneProduct ensembl:ENSMUSG00000026701
Prdx6b GeneProduct ensembl:ENSMUSG00000050114
Ptgs1 GeneProduct ensembl:ENSMUSG00000047250
Ptgs2 GeneProduct ensembl:ENSMUSG00000032487
S100a8 GeneProduct ensembl:ENSMUSG00000056054
S100a9 GeneProduct ensembl:ENSMUSG00000056071
Sod1 GeneProduct ensembl:ENSMUSG00000022982
Sod2 GeneProduct ensembl:ENSMUSG00000006818
Sod3 GeneProduct ensembl:ENSMUSG00000072941
Txnrd1 GeneProduct ensembl:ENSMUSG00000020250
Txnrd2 GeneProduct ensembl:ENSMUSG00000075704
Txnrd3 GeneProduct ensembl:ENSMUSG00000000811

References

  1. Nrf1 and Nrf2 regulate rat glutamate-cysteine ligase catalytic subunit transcription indirectly via NF-kappaB and AP-1. Yang H, Magilnick N, Lee C, Kalmaz D, Ou X, Chan JY, et al. Mol Cell Biol. 2005 Jul;25(14):5933–46. PubMed Europe PMC Scholia
  2. Plasma membrane glutathione transporters and their roles in cell physiology and pathophysiology. Ballatori N, Krance SM, Marchan R, Hammond CL. Mol Aspects Med. 2009;30(1–2):13–28. PubMed Europe PMC Scholia
  3. A genomewide functional network for the laboratory mouse. Guan Y, Myers CL, Lu R, Lemischka IR, Bult CJ, Troyanskaya OG. PLoS Comput Biol. 2008 Sep 26;4(9):e1000165. PubMed Europe PMC Scholia
  4. Stress-activated cap’n’collar transcription factors in aging and human disease. Sykiotis GP, Bohmann D. Sci Signal. 2010 Mar 9;3(112):re3. PubMed Europe PMC Scholia
  5. Regulatory T cells interfere with glutathione metabolism in dendritic cells and T cells. Yan Z, Garg SK, Banerjee R. J Biol Chem. 2010 Dec 31;285(53):41525–32. PubMed Europe PMC Scholia
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  7. Glutathione redox dynamics and expression of glutathione-related genes in the developing embryo. Timme-Laragy AR, Goldstone JV, Imhoff BR, Stegeman JJ, Hahn ME, Hansen JM. Free Radic Biol Med. 2013 Dec;65:89–101. PubMed Europe PMC Scholia
  8. Modulation of oxidative stress as an anticancer strategy. Gorrini C, Harris IS, Mak TW. Nat Rev Drug Discov. 2013 Dec;12(12):931–47. PubMed Europe PMC Scholia
  9. The Nrf2 regulatory network provides an interface between redox and intermediary metabolism. Hayes JD, Dinkova-Kostova AT. Trends Biochem Sci. 2014 Apr;39(4):199–218. PubMed Europe PMC Scholia
  10. Nrf2-dysregulation correlates with reduced synthesis and low glutathione levels in experimental autoimmune encephalomyelitis. Morales Pantoja IE, Hu CL, Perrone-Bizzozero NI, Zheng J, Bizzozero OA. J Neurochem. 2016 Nov;139(4):640–50. PubMed Europe PMC Scholia
  11. Transcriptional profiling and therapeutic targeting of oxidative stress in neuroinflammation. Mendiola AS, Ryu JK, Bardehle S, Meyer-Franke A, Ang KKH, Wilson C, et al. Nat Immunol. 2020 May;21(5):513–24. PubMed Europe PMC Scholia