Oxidative stress and redox pathway (Mus musculus)

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11105665, 67599583, 922BiosynthesisGlutathionylationRedox cycleTxn1Prdx1Gpx5Keap1GSH conjugatesGlutamineGrxcr2GlutamateNADPHCd444GssOplahNADP+Slc1a2SerineSlc7a11H2OFoxp3Gsto1H2O2CystineGSHGstp1Glutamyl amino acidGlycineGpx1 Slc1a5Grxcr1CysteineGSSGGpx4Gpx2acivicinO2g-GlutamylcysteineG6pdxSlc6a9Gclc5-OxoprolineNrf2Alox5Nrf1Gstt1Gsta1GsrCbsIdh1Mgst1Gstm2GlsGclmGgctGpx3Gpx6Gpx7Gpx8Idh2G6pd2PgdNrf25GlutamineGstt2Gstt3Gstm1Gstm3Gstm4Gstm5Gstm6Gstm7Gsta2Gsta3Gsta4Gstp2Gsto2Mgst2Mgst3HpgdsGstk1CystineGlutamateGSHCysteineHomocysteineGgt5Ggt6Ggt7Ggt1GlutamateGlutamateAbcc2Abcc5Keap1Amino acidGlutamylamino acidLap3AnpepGlycineGlutamate exportvia Slc7a11Slc6a5Cysteinyl-glycineNrf1Slco1a1Slco2a1Ctla41CybbCybaRac1Ncf4Ncf1Ncf2O2-GTPNADPHNADP+Prdx2Prdx3Prdx4Prdx5Prdx6Prdx6bPtgs1Ptgs2S100a8S100a9Sod1Sod2Sod3Txnrd1Txnrd2Txnrd3H2OH2O2O2O2-


Description

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 WP164 and WP1770, with information added from literature.

This pathway was created as a part of Mendiola et cl, pictured in fig 5.

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Quality Tags

Ontology Terms

 

Bibliography

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  1. Yan Z, Garg SK, Banerjee R; ''Regulatory T cells interfere with glutathione metabolism in dendritic cells and T cells.''; J Biol Chem, 2010 PubMed Europe PMC Scholia
  2. Morales Pantoja IE, Hu CL, Perrone-Bizzozero NI, Zheng J, Bizzozero OA; ''Nrf2-dysregulation correlates with reduced synthesis and low glutathione levels in experimental autoimmune encephalomyelitis.''; J Neurochem, 2016 PubMed Europe PMC Scholia
  3. Ballatori N, Krance SM, Marchan R, Hammond CL; ''Plasma membrane glutathione transporters and their roles in cell physiology and pathophysiology.''; Mol Aspects Med, 2009 PubMed Europe PMC Scholia
  4. Gorrini C, Harris IS, Mak TW; ''Modulation of oxidative stress as an anticancer strategy.''; Nat Rev Drug Discov, 2013 PubMed Europe PMC Scholia
  5. Hayes JD, Dinkova-Kostova AT; ''The Nrf2 regulatory network provides an interface between redox and intermediary metabolism.''; Trends Biochem Sci, 2014 PubMed Europe PMC Scholia
  6. Yang H, Magilnick N, Lee C, Kalmaz D, Ou X, Chan JY, Lu SC; ''Nrf1 and Nrf2 regulate rat glutamate-cysteine ligase catalytic subunit transcription indirectly via NF-kappaB and AP-1.''; Mol Cell Biol, 2005 PubMed Europe PMC Scholia
  7. Guan Y, Myers CL, Lu R, Lemischka IR, Bult CJ, Troyanskaya OG; ''A genomewide functional network for the laboratory mouse.''; PLoS Comput Biol, 2008 PubMed Europe PMC Scholia
  8. Sykiotis GP, Bohmann D; ''Stress-activated cap'n'collar transcription factors in aging and human disease.''; Sci Signal, 2010 PubMed Europe PMC Scholia
  9. Timme-Laragy AR, Goldstone JV, Imhoff BR, Stegeman JJ, Hahn ME, Hansen JM; ''Glutathione redox dynamics and expression of glutathione-related genes in the developing embryo.''; Free Radic Biol Med, 2013 PubMed Europe PMC Scholia
  10. Lushchak VI; ''Glutathione homeostasis and functions: potential targets for medical interventions.''; J Amino Acids, 2012 PubMed Europe PMC Scholia
  11. Andrew S. Mendiola, Jae Kyu Ryu, Sophia Bardehle, Anke Meyer-Franke, Kenny Kean-Hooi Ang, Chris Wilson, Kim M. Baeten, Kristina Hanspers, Mario Merlini, Sean Thomas, Mark A. Petersen, Alexander Williams, Reuben Thomas, Victoria A. Rafalski, Rosa Meza-Acevedo, Reshmi Tognatta, Zhaoqi Yan, Samuel J. Pfaff, Michael R. Machado, Catherine Bedard, Pamela E. Rios Coronado, Xiqian Jiang, Jin Wang, Michael A. Pleiss, Ari J. Green, Scott S. Zamvil, Alexander R. Pico, Benoit G. Bruneau, Michelle R. Arkin, Katerina Akassoglou; ''Transcriptional profiling and therapeutic targeting of oxidative stress in neuroinflammation''; , 2020 PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
125303view17:44, 31 January 2023LarsgwAdd PMID to reference
116840view10:31, 14 May 2021EweitzModified title
113759view15:17, 19 November 2020DeSlUpdated old HMDB IDs
113643view18:16, 9 November 2020EgonwUpdated HMDB identifiers.
110030view17:02, 13 April 2020KhanspersModified description
110029view17:00, 13 April 2020Khanspers
109791view04:19, 1 April 2020AlexanderPicoOntology Term : 'classic metabolic pathway' added !
109790view04:19, 1 April 2020AlexanderPicoOntology Term : 'PW:0000134' removed !
109789view04:18, 1 April 2020AlexanderPicoModified title
102048view00:17, 27 November 2018KhanspersModified description
101900view00:49, 16 November 2018KhanspersOntology Term : 'glutathione biosynthetic pathway' added !
101899view00:49, 16 November 2018KhanspersOntology Term : 'glutathione antioxidant pathway' added !
101898view00:48, 16 November 2018KhanspersModified description
101897view00:45, 16 November 2018KhanspersModified title
101896view23:37, 15 November 2018KhanspersOntology Term : 'glutathione metabolic pathway' added !
101895view23:36, 15 November 2018KhanspersModified description
101894view23:35, 15 November 2018Khanspersremoved GenMAPP comments
101893view23:31, 15 November 2018KhanspersNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
Slc1a5GeneProductENSMUSG00000001918 (Ensembl)
5-OxoprolineMetaboliteC01879 (KEGG Compound)
Abcc2GeneProductENSMUSG00000025194 (Ensembl)
Abcc5GeneProductENSMUSG00000022822 (Ensembl)
Alox5GeneProductENSMUSG00000025701 (Ensembl)
Amino acidMetaboliteC00151 (KEGG Compound)
AnpepGeneProductENSMUSG00000039062 (Ensembl)
CbsGeneProductENSMUSG00000024039 (Ensembl)
Cd44GeneProductENSMUSG00000005087 (Ensembl) CD44 interacts with and stabilizes XCT
Ctla4GeneProductENSMUSG00000026011 (Ensembl)
CybaGeneProductENSMUSG00000006519 (Ensembl)
CybbGeneProductENSMUSG00000015340 (Ensembl)
CysteineMetaboliteC00097 (KEGG Compound)
CysteineMetaboliteHMDB0000574 (HMDB)
Cysteinyl-glycineMetaboliteC01419 (KEGG Compound)
CystineMetaboliteHMDB0000192 (HMDB)
Foxp3GeneProductENSMUSG00000039521 (Ensembl)
G6pd2GeneProductENSMUSG00000089992 (Ensembl)
G6pdxGeneProductENSMUSG00000031400 (Ensembl)
GSH conjugatesMetaboliteC02320 (KEGG Compound)
GSHMetaboliteC00051 (KEGG Compound)
GSSGMetabolite27025-41-8 (CAS)
GTPMetaboliteCHEBI:15996 (ChEBI)
GclcGeneProductENSMUSG00000032350 (Ensembl)
GclmGeneProductENSMUSG00000028124 (Ensembl)
GgctGeneProductENSMUSG00000002797 (Ensembl)
Ggt1GeneProductENSMUSG00000006345 (Ensembl) (5-L-Glutamyl)-L-amino acid
Ggt5GeneProductENSMUSG00000006344 (Ensembl)
Ggt6GeneProductENSMUSG00000040471 (Ensembl)
Ggt7GeneProductENSMUSG00000027603 (Ensembl)
GlsGeneProductENSMUSG00000026103 (Ensembl)
GlutamateMetaboliteHMDB0000148 (HMDB)
GlutamineMetaboliteHMDB0000641 (HMDB)
Glutamyl amino acidMetaboliteC03740 (KEGG Compound)
Glutamyl amino acidMetaboliteC03740 (KEGG Compound)
GlycineMetaboliteHMDB0000123 (HMDB)
Gpx1GeneProductENSMUSG00000063856 (Ensembl)
Gpx2GeneProductENSMUSG00000042808 (Ensembl)
Gpx3GeneProductENSMUSG00000018339 (Ensembl)
Gpx4GeneProductENSMUSG00000075706 (Ensembl)
Gpx5GeneProductENSMUSG00000004344 (Ensembl)
Gpx6GeneProductENSMUSG00000004341 (Ensembl)
Gpx7GeneProductENSMUSG00000028597 (Ensembl)
Gpx8GeneProductENSMUSG00000021760 (Ensembl)
Grxcr1GeneProductENSMUSG00000068082 (Ensembl)
Grxcr2GeneProductENSMUSG00000073574 (Ensembl)
GsrGeneProductENSMUSG00000031584 (Ensembl)
GssGeneProductENSMUSG00000027610 (Ensembl)
Gsta1GeneProductENSMUSG00000074183 (Ensembl)
Gsta2GeneProductENSMUSG00000057933 (Ensembl)
Gsta3GeneProductENSMUSG00000025934 (Ensembl)
Gsta4GeneProductENSMUSG00000032348 (Ensembl)
Gstk1GeneProductENSMUSG00000029864 (Ensembl)
Gstm1GeneProductENSMUSG00000058135 (Ensembl)
Gstm2GeneProductENSMUSG00000040562 (Ensembl)
Gstm3GeneProductENSMUSG00000004038 (Ensembl)
Gstm4GeneProductENSMUSG00000027890 (Ensembl)
Gstm5GeneProductENSMUSG00000004032 (Ensembl)
Gstm6GeneProductENSMUSG00000068762 (Ensembl)
Gstm7GeneProductENSMUSG00000004035 (Ensembl)
Gsto1GeneProductENSMUSG00000025068 (Ensembl)
Gsto2GeneProductENSMUSG00000025069 (Ensembl)
Gstp1GeneProductENSMUSG00000060803 (Ensembl)
Gstp2GeneProductENSMUSG00000038155 (Ensembl)
Gstt1GeneProductENSMUSG00000001663 (Ensembl)
Gstt2GeneProductENSMUSG00000033318 (Ensembl)
Gstt3GeneProductENSMUSG00000001665 (Ensembl)
H2O2MetaboliteHMDB0003125 (HMDB)
H2OMetaboliteHMDB0002111 (HMDB)
HomocysteineMetaboliteHMDB0000742 (HMDB)
HpgdsGeneProductENSMUSG00000029919 (Ensembl)
Idh1GeneProductENSMUSG00000025950 (Ensembl)
Idh2GeneProductENSMUSG00000030541 (Ensembl)
Keap1GeneProductENSMUSG00000003308 (Ensembl)
Lap3GeneProductENSMUSG00000039682 (Ensembl)
Mgst1GeneProductENSMUSG00000008540 (Ensembl)
Mgst2GeneProductENSMUSG00000074604 (Ensembl)
Mgst3GeneProductENSMUSG00000026688 (Ensembl)
NADP+MetaboliteHMDB0000217 (HMDB)
NADPHMetaboliteHMDB0000221 (HMDB)
Ncf1GeneProductENSMUSG00000015950 (Ensembl)
Ncf2GeneProductENSMUSG00000026480 (Ensembl)
Ncf4GeneProductENSMUSG00000071715 (Ensembl)
Nrf1GeneProductENSMUSG00000058440 (Ensembl)
Nrf2GeneProductENSMUSG00000015839 (Ensembl)
O2-MetaboliteCHEBI:18421 (ChEBI)
O2MetaboliteCHEBI:15379 (ChEBI)
OplahGeneProductENSMUSG00000022562 (Ensembl)
PgdGeneProductENSMUSG00000028961 (Ensembl)
Prdx1GeneProductENSMUSG00000028691 (Ensembl)
Prdx2GeneProductENSMUSG00000005161 (Ensembl)
Prdx3GeneProductENSMUSG00000024997 (Ensembl)
Prdx4GeneProductENSMUSG00000025289 (Ensembl)
Prdx5GeneProductENSMUSG00000024953 (Ensembl)
Prdx6GeneProductENSMUSG00000026701 (Ensembl)
Prdx6bGeneProductENSMUSG00000050114 (Ensembl)
Ptgs1GeneProductENSMUSG00000047250 (Ensembl)
Ptgs2GeneProductENSMUSG00000032487 (Ensembl)
Rac1GeneProductENSMUSG00000001847 (Ensembl)
S100a8GeneProductENSMUSG00000056054 (Ensembl)
S100a9GeneProductENSMUSG00000056071 (Ensembl)
SerineMetaboliteHMDB0000187 (HMDB)
Slc1a2GeneProductENSMUSG00000005089 (Ensembl)
Slc6a5GeneProductENSMUSG00000039728 (Ensembl)
Slc6a9GeneProductENSMUSG00000028542 (Ensembl)
Slc7a11GeneProductENSMUSG00000027737 (Ensembl) System Xc- is an antiporter that transports Cystine in and glutamate out. https://en.wikipedia.org/wiki/SLC7A11
Slco1a1GeneProductENSMUSG00000041698 (Ensembl)
Slco2a1GeneProductENSMUSG00000032548 (Ensembl)
Sod1GeneProductENSMUSG00000022982 (Ensembl)
Sod2GeneProductENSMUSG00000006818 (Ensembl)
Sod3GeneProductENSMUSG00000072941 (Ensembl)
Txn1GeneProductENSMUSG00000028367 (Ensembl)
Txnrd1GeneProductENSMUSG00000020250 (Ensembl)
Txnrd2GeneProductENSMUSG00000075704 (Ensembl)
Txnrd3GeneProductENSMUSG00000000811 (Ensembl)
acivicinMetaboliteCHEBI:74545 (ChEBI)
g-GlutamylcysteineMetaboliteC00669 (KEGG Compound)

Annotated Interactions

No annotated interactions

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