Oxidative stress and redox pathway (WP4466)

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.
last edited

Authors

Khanspers, AlexanderPico, Egonw, DeSl, and Eweitz

Cited In

Organism

Mus musculus

Communities

Annotations

Pathway Ontology: glutathione antioxidant pathway glutathione biosynthetic pathway glutathione metabolic pathway classic metabolic pathway

Participants

Label Type Compact Identifier
Gpx5 GeneProduct ensembl:ENSMUSG00000004344
Prdx1 GeneProduct ensembl:ENSMUSG00000028691
Txn1 GeneProduct ensembl:ENSMUSG00000028367
Keap1 GeneProduct ensembl:ENSMUSG00000003308
GSH conjugates Metabolite kegg.compound:C02320
Glutamine Metabolite hmdb:HMDB0000641
Grxcr2 GeneProduct ensembl:ENSMUSG00000073574
Glutamate Metabolite hmdb:HMDB0000148
NADPH Metabolite hmdb:HMDB0000221
Cd44 GeneProduct ensembl:ENSMUSG00000005087
Gss GeneProduct ensembl:ENSMUSG00000027610
Oplah GeneProduct ensembl:ENSMUSG00000022562
NADP+ Metabolite hmdb:HMDB0000217
Slc1a2 GeneProduct ensembl:ENSMUSG00000005089
Serine Metabolite hmdb:HMDB0000187
Slc7a11 GeneProduct ensembl:ENSMUSG00000027737
H2O Metabolite hmdb:HMDB0002111
Foxp3 GeneProduct ensembl:ENSMUSG00000039521
Gsto1 GeneProduct ensembl:ENSMUSG00000025068
H2O2 Metabolite hmdb:HMDB0003125
Cystine Metabolite hmdb:HMDB0000192
GSH Metabolite kegg.compound:C00051
Gstp1 GeneProduct ensembl:ENSMUSG00000060803
Glutamyl amino acid Metabolite kegg.compound:C03740
Glycine Metabolite hmdb:HMDB0000123
Gpx1 GeneProduct ensembl:ENSMUSG00000063856
Slc1a5 GeneProduct ensembl:ENSMUSG00000001918
Grxcr1 GeneProduct ensembl:ENSMUSG00000068082
Cysteine Metabolite kegg.compound:C00097
GSSG Metabolite cas:27025-41-8
Gpx4 GeneProduct ensembl:ENSMUSG00000075706
Gpx2 GeneProduct ensembl:ENSMUSG00000042808
acivicin Metabolite chebi:74545
O2 Metabolite chebi:15379
g-Glutamylcysteine Metabolite kegg.compound:C00669
G6pdx GeneProduct ensembl:ENSMUSG00000031400
Slc6a9 GeneProduct ensembl:ENSMUSG00000028542
Gclc GeneProduct ensembl:ENSMUSG00000032350
5-Oxoproline Metabolite kegg.compound:C01879
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
Nrf2 GeneProduct ensembl:ENSMUSG00000015839
Glutamine Metabolite hmdb:HMDB0000641
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
Cystine Metabolite hmdb:HMDB0000192
Glutamate Metabolite hmdb:HMDB0000148
GSH Metabolite kegg.compound:C00051
Cysteine Metabolite hmdb:HMDB0000574
Homocysteine Metabolite hmdb:HMDB0000742
Ggt5 GeneProduct ensembl:ENSMUSG00000006344
Ggt6 GeneProduct ensembl:ENSMUSG00000040471
Ggt7 GeneProduct ensembl:ENSMUSG00000027603
Ggt1 GeneProduct ensembl:ENSMUSG00000006345
Glutamate Metabolite hmdb:HMDB0000148
Glutamate Metabolite hmdb:HMDB0000148
Abcc2 GeneProduct ensembl:ENSMUSG00000025194
Abcc5 GeneProduct ensembl:ENSMUSG00000022822
Keap1 GeneProduct ensembl:ENSMUSG00000003308
Amino acid Metabolite kegg.compound:C00151
Glutamylamino acid Metabolite kegg.compound:C03740
Lap3 GeneProduct ensembl:ENSMUSG00000039682
Anpep GeneProduct ensembl:ENSMUSG00000039062
Glycine Metabolite hmdb:HMDB0000123
Slc6a5 GeneProduct ensembl:ENSMUSG00000039728
Cysteinyl-glycine Metabolite kegg.compound:C01419
Nrf1 GeneProduct ensembl:ENSMUSG00000058440
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
O2- Metabolite chebi:18421
GTP Metabolite chebi:15996
NADPH Metabolite hmdb:HMDB0000221
NADP+ Metabolite hmdb:HMDB0000217
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
H2O Metabolite hmdb:HMDB0002111
H2O2 Metabolite hmdb:HMDB0003125
O2 Metabolite chebi:15379
O2- Metabolite chebi:18421

References

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  4. Sykiotis GP, Bohmann D. Stress-activated cap’n’collar transcription factors in aging and human disease. Sci Signal. 2010 Mar 9;3(112):re3. PubMed Europe PMC Scholia
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  8. Gorrini C, Harris IS, Mak TW. Modulation of oxidative stress as an anticancer strategy. Nat Rev Drug Discov. 2013 Dec;12(12):931–47. PubMed Europe PMC Scholia
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  10. Morales Pantoja IE, Hu C-L, Perrone-Bizzozero NI, Zheng J, Bizzozero OA. Nrf2-dysregulation correlates with reduced synthesis and low glutathione levels in experimental autoimmune encephalomyelitis. J Neurochem. 2016 Nov;139(4):640–50. PubMed Europe PMC Scholia