Detoxification of reactive oxygen species (Homo sapiens)

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1, 6, 7, 46-49, 62...5, 23, 9127, 32, 83, 8521, 42, 67, 78, 84...4, 51, 54, 6343, 6010, 53, 5615, 21, 42, 67, 78...4, 8935, 51, 54115929, 6457, 7012, 18, 24, 923, 808, 25, 34, 37, 75...31, 871330, 40, 59, 65688917, 22, 25, 39, 55...5226, 28, 72, 9036, 45, 7450, 61, 865, 23, 41, 44, 66...19, 382, 71, 8116, 66mitochondrionGolgi lumencytosolendoplasmic reticulum lumenperoxisomal matrixmitochondrial matrixL-selenocysteine residue-GPX1 O2.-PeroxynitriteO2Cu1+ TXNRD2 H2ONADPHZn2+ GTPH+Cytochrome c(reduced)H+ATPPRDX6:GSTP1H2OGPX5 NADP+GPX2 AQP8 tetramerTXNRD2 dimerCCS SOD1 Cu2+ H2OGSHNADPHTXN2Cu1+ CAT tetramerPRDX1 ATP7AGSR-1 GPX3 tetramerO2.-Cytochrome c(oxidised)CYBB Cu1+ SOD1 dimerH2ONOX5 NADPHNADPHCCS:Cu1+ dimerATOX1:Cu1+GSSGFAD H+H2OCu2+ Zn2+ H2OCu2+ CCS Cu1+ CYCS SOD1 GSR-2 PRDX5-1 PRDX5-1SOD3 CCS dimerH2O2NitriteH2ONOX4 GSTP1 H2OZn2+ O2H2OSOD3 (19-227) SOD3 H+FAD FAD NADPHZn2+ H+PRDX3 Zn2+ H2O2CCS PiMn2+ CCS CCS:SOD1 dimerNADP+PRDX2 H+P4HBSOD2 GPX2 tetramerSOD2 tetramerNUDT2Cu1+ GSSGNOheme PRDX1,2,5GPX1 tetramerZn2+ CCS:SOD1GSHH2O2O2NADP+SOD1 dimerCu1+ ERO1L:GPX7,8H2O2GSHHC53,56-P4HBPRDX3,5ATOX1 ADPO2.-ferroheme Zn2+ Cu2+ FAD O2H+ferriheme ERO1L 2xHC-TXNGP4GNADPH CCS:Cu1+ dimerGPX8 PRDX6 SOD32xHC-SOD1 SOD3 tetramerPRDX5 NADP+CYBA O2TXNRD1 NitriteNAD+CYCS NOX4, NOX5H2O2Zn2+ H2OZn2+ GSSGZn2+O2-NONADP+GSR dimerH+Zn2+ GPX5, (GPX6)H2O2AQP8 PeroxynitriteGPX6 GPX7 L-selenoC49-GPX1 L-selenoC73-GPX3 SOD12xHC-SOD1 H2OGMPCCS GSR-2:FAD dimerATOX1Cu1+ PRDX5Zn2+ CAT 2xHC-TXN2CCS TNXRD1:FAD dimerSOD1 CCS dimerTXNSOD3 tetramerSOD1:Zn2+GPX1 tetramer749514, 20, 9964749720, 76438279, 948112, 20, 77644410, 43, 53, 5679, 944450, 612, 3310, 53, 5612, 209, 2650, 6150, 618214, 10043, 101


Description

Reactive oxygen species such as superoxide (O2.-), peroxides (ROOR), singlet oxygen, peroxynitrite (ONOO-), and hydroxyl radical (OH.) are generated by cellular processes such as respiration (reviewed in Murphy 2009, Brand 2010) and redox enzymes and are required for signaling yet they are damaging due to their high reactivity (reviewed in Imlay 2008, Buettner 2011, Kavdia 2011, Birben et al. 2012, Ray et al. 2012). Aerobic cells have defenses that detoxify reactive oxygen species by converting them to less reactive products. Superoxide dismutases convert superoxide to hydrogen peroxide and oxygen (reviewed in Fukai and Ushio-Fukai 2011). Catalase and peroxidases then convert hydrogen peroxide to water.
Humans contain 3 superoxide dismutases: SOD1 is located in the cytosol and mitochondrial intermembrane space, SOD2 is located in the mitochondrial matrix, and SOD3 is located in the extracellular region. Superoxide, a negative ion, is unable to easily cross membranes and tends to remain in the compartment where it was produced. Hydrogen peroxide, one of the products of superoxide dismutase, is able to diffuse across membranes and pass through aquaporin channels. In most cells the primary source of hydrogen peroxide is mitochondria and, once in the cytosol, hydrogen peroxide serves as a signaling molecule to regulate redox-sensitive proteins such as transcription factors, kinases, phosphatases, ion channels, and others (reviewed in Veal and Day 2011, Ray et al. 2012). Hydrogen peroxide is decomposed to water by catalase, decomposed to water plus oxidized thioredoxin by peroxiredoxins, and decomposed to water plus oxidized glutathione by glutathione peroxidases (Presnell et al. 2013). View original pathway at:Reactome.

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  1. Allen S, Badarau A, Dennison C.; ''Cu(I) affinities of the domain 1 and 3 sites in the human metallochaperone for Cu,Zn-superoxide dismutase.''; PubMed Europe PMC Scholia
  2. Martyn KD, Frederick LM, von Loehneysen K, Dinauer MC, Knaus UG.; ''Functional analysis of Nox4 reveals unique characteristics compared to other NADPH oxidases.''; PubMed Europe PMC Scholia
  3. Packer MA, Porteous CM, Murphy MP.; ''Superoxide production by mitochondria in the presence of nitric oxide forms peroxynitrite.''; PubMed Europe PMC Scholia
  4. Takahashi K, Avissar N, Whitin J, Cohen H.; ''Purification and characterization of human plasma glutathione peroxidase: a selenoglycoprotein distinct from the known cellular enzyme.''; PubMed Europe PMC Scholia
  5. Silverman DN, Nick HS.; ''Catalytic pathway of manganese superoxide dismutase by direct observation of superoxide.''; PubMed Europe PMC Scholia
  6. Maddipati KR, Marnett LJ.; ''Characterization of the major hydroperoxide-reducing activity of human plasma. Purification and properties of a selenium-dependent glutathione peroxidase.''; PubMed Europe PMC Scholia
  7. Awasthi YC, Beutler E, Srivastava SK.; ''Purification and properties of human erythrocyte glutathione peroxidase.''; PubMed Europe PMC Scholia
  8. Werber MM, Greenstein LA.; ''Biochemical and stability properties of recombinant human MnSOD.''; PubMed Europe PMC Scholia
  9. Birben E, Sahiner UM, Sackesen C, Erzurum S, Kalayci O.; ''Oxidative stress and antioxidant defense.''; PubMed Europe PMC Scholia
  10. Matsuda Y, Suzuki K, Ookawara T, Nakata T, Seo HG, Kawata S, Tarui S, Deutsch HF, Taniguchi N.; ''A three-step purification of manganese superoxide dismutase from human liver on both large and small scales.''; PubMed Europe PMC Scholia
  11. Babior BM.; ''NADPH oxidase: an update.''; PubMed Europe PMC Scholia
  12. McCord JM, Fridovich I.; ''Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein).''; PubMed Europe PMC Scholia
  13. BelAiba RS, Djordjevic T, Petry A, Diemer K, Bonello S, Banfi B, Hess J, Pogrebniak A, Bickel C, Görlach A.; ''NOX5 variants are functionally active in endothelial cells.''; PubMed Europe PMC Scholia
  14. Nagy P, Karton A, Betz A, Peskin AV, Pace P, O'Reilly RJ, Hampton MB, Radom L, Winterbourn CC.; ''Model for the exceptional reactivity of peroxiredoxins 2 and 3 with hydrogen peroxide: a kinetic and computational study.''; PubMed Europe PMC Scholia
  15. Faucher K, Rabinovitch-Chable H, Barrière G, Cook-Moreau J, Rigaud M.; ''Overexpression of cytosolic glutathione peroxidase (GPX1) delays endothelial cell growth and increases resistance to toxic challenges.''; PubMed Europe PMC Scholia
  16. Dinauer MC, Pierce EA, Erickson RW, Muhlebach TJ, Messner H, Orkin SH, Seger RA, Curnutte JT.; ''Point mutation in the cytoplasmic domain of the neutrophil p22-phox cytochrome b subunit is associated with a nonfunctional NADPH oxidase and chronic granulomatous disease.''; PubMed Europe PMC Scholia
  17. Huie RE, Padmaja S.; ''The reaction of no with superoxide.''; PubMed Europe PMC Scholia
  18. Sandström J, Karlsson K, Edlund T, Marklund SL.; ''Heparin-affinity patterns and composition of extracellular superoxide dismutase in human plasma and tissues.''; PubMed Europe PMC Scholia
  19. Sugiura M, Adachi T, Inoue H, Ito Y, Hirano K.; ''Purification of superoxide dismutases from human placenta using immunoadsorbent columns.''; PubMed Europe PMC Scholia
  20. Pryor WA, Squadrito GL.; ''The chemistry of peroxynitrite: a product from the reaction of nitric oxide with superoxide.''; PubMed Europe PMC Scholia
  21. Zhou S, Lien YC, Shuvaeva T, DeBolt K, Feinstein SI, Fisher AB.; ''Functional interaction of glutathione S-transferase pi and peroxiredoxin 6 in intact cells.''; PubMed Europe PMC Scholia
  22. Kavdia M.; ''Mathematical and computational models of oxidative and nitrosative stress.''; PubMed Europe PMC Scholia
  23. Olsen DA, Petersen SV, Oury TD, Valnickova Z, Thøgersen IB, Kristensen T, Bowler RP, Crapo JD, Enghild JJ.; ''The intracellular proteolytic processing of extracellular superoxide dismutase (EC-SOD) is a two-step event.''; PubMed Europe PMC Scholia
  24. Urig S, Lieske J, Fritz-Wolf K, Irmler A, Becker K.; ''Truncated mutants of human thioredoxin reductase 1 do not exhibit glutathione reductase activity.''; PubMed Europe PMC Scholia
  25. Ottaviano FG, Tang SS, Handy DE, Loscalzo J.; ''Regulation of the extracellular antioxidant selenoprotein plasma glutathione peroxidase (GPx-3) in mammalian cells.''; PubMed Europe PMC Scholia
  26. Carroll MC, Outten CE, Proescher JB, Rosenfeld L, Watson WH, Whitson LJ, Hart PJ, Jensen LT, Cizewski Culotta V.; ''The effects of glutaredoxin and copper activation pathways on the disulfide and stability of Cu,Zn superoxide dismutase.''; PubMed Europe PMC Scholia
  27. Han D, Williams E, Cadenas E.; ''Mitochondrial respiratory chain-dependent generation of superoxide anion and its release into the intermembrane space.''; PubMed Europe PMC Scholia
  28. Buettner GR.; ''Superoxide dismutase in redox biology: the roles of superoxide and hydrogen peroxide.''; PubMed Europe PMC Scholia
  29. Antico Arciuch VG, Elguero ME, Poderoso JJ, Carreras MC.; ''Mitochondrial regulation of cell cycle and proliferation.''; PubMed Europe PMC Scholia
  30. Puente-Maestu L, Tejedor A, Lázaro A, de Miguel J, Alvarez-Sala L, González-Aragoneses F, Simón C, Agustí A.; ''Site of mitochondrial reactive oxygen species production in skeletal muscle of chronic obstructive pulmonary disease and its relationship with exercise oxidative stress.''; PubMed Europe PMC Scholia
  31. Boveris A, Valdez LB, Zaobornyj T, Bustamante J.; ''Mitochondrial metabolic states regulate nitric oxide and hydrogen peroxide diffusion to the cytosol.''; PubMed Europe PMC Scholia
  32. Li S, Yan T, Yang JQ, Oberley TD, Oberley LW.; ''The role of cellular glutathione peroxidase redox regulation in the suppression of tumor cell growth by manganese superoxide dismutase.''; PubMed Europe PMC Scholia
  33. Ogata M.; ''Acatalasemia.''; PubMed Europe PMC Scholia
  34. Ren B, Huang W, Akesson B, Ladenstein R.; ''The crystal structure of seleno-glutathione peroxidase from human plasma at 2.9 A resolution.''; PubMed Europe PMC Scholia
  35. Rae TD, Torres AS, Pufahl RA, O'Halloran TV.; ''Mechanism of Cu,Zn-superoxide dismutase activation by the human metallochaperone hCCS.''; PubMed Europe PMC Scholia
  36. Oury TD, Crapo JD, Valnickova Z, Enghild JJ.; ''Human extracellular superoxide dismutase is a tetramer composed of two disulphide-linked dimers: a simplified, high-yield purification of extracellular superoxide dismutase.''; PubMed Europe PMC Scholia
  37. Mishina NM, Tyurin-Kuzmin PA, Markvicheva KN, Vorotnikov AV, Tkachuk VA, Laketa V, Schultz C, Lukyanov S, Belousov VV.; ''Does cellular hydrogen peroxide diffuse or act locally?''; PubMed Europe PMC Scholia
  38. Carreras MC, Poderoso JJ.; ''Mitochondrial nitric oxide in the signaling of cell integrated responses.''; PubMed Europe PMC Scholia
  39. Korshunov SS, Skulachev VP, Starkov AA.; ''High protonic potential actuates a mechanism of production of reactive oxygen species in mitochondria.''; PubMed Europe PMC Scholia
  40. Lee W, Choi KS, Riddell J, Ip C, Ghosh D, Park JH, Park YM.; ''Human peroxiredoxin 1 and 2 are not duplicate proteins: the unique presence of CYS83 in Prx1 underscores the structural and functional differences between Prx1 and Prx2.''; PubMed Europe PMC Scholia
  41. Koppenol WH, van Buuren KJ, Butler J, Braams R.; ''The kinetics of the reduction of cytochrome c by the superoxide anion radical.''; PubMed Europe PMC Scholia
  42. Cao Z, Bhella D, Lindsay JG.; ''Reconstitution of the mitochondrial PrxIII antioxidant defence pathway: general properties and factors affecting PrxIII activity and oligomeric state.''; PubMed Europe PMC Scholia
  43. Bosello-Travain V, Conrad M, Cozza G, Negro A, Quartesan S, Rossetto M, Roveri A, Toppo S, Ursini F, Zaccarin M, Maiorino M.; ''Protein disulfide isomerase and glutathione are alternative substrates in the one Cys catalytic cycle of glutathione peroxidase 7.''; PubMed Europe PMC Scholia
  44. Okado-Matsumoto A, Fridovich I.; ''Subcellular distribution of superoxide dismutases (SOD) in rat liver: Cu,Zn-SOD in mitochondria.''; PubMed Europe PMC Scholia
  45. Smeets A, Evrard C, Landtmeters M, Marchand C, Knoops B, Declercq JP.; ''Crystal structures of oxidized and reduced forms of human mitochondrial thioredoxin 2.''; PubMed Europe PMC Scholia
  46. Yamashita H, Avraham S, Jiang S, London R, Van Veldhoven PP, Subramani S, Rogers RA, Avraham H.; ''Characterization of human and murine PMP20 peroxisomal proteins that exhibit antioxidant activity in vitro.''; PubMed Europe PMC Scholia
  47. Veal E, Day A.; ''Hydrogen peroxide as a signaling molecule.''; PubMed Europe PMC Scholia
  48. Matsuda Y, Higashiyama S, Kijima Y, Suzuki K, Kawano K, Akiyama M, Kawata S, Tarui S, Deutsch HF, Taniguchi N.; ''Human liver manganese superoxide dismutase. Purification and crystallization, subunit association and sulfhydryl reactivity.''; PubMed Europe PMC Scholia
  49. Chung SS, Kim M, Youn BS, Lee NS, Park JW, Lee IK, Lee YS, Kim JB, Cho YM, Lee HK, Park KS.; ''Glutathione peroxidase 3 mediates the antioxidant effect of peroxisome proliferator-activated receptor gamma in human skeletal muscle cells.''; PubMed Europe PMC Scholia
  50. Banci L, Bertini I, Cantini F, Kozyreva T, Massagni C, Palumaa P, Rubino JT, Zovo K.; ''Human superoxide dismutase 1 (hSOD1) maturation through interaction with human copper chaperone for SOD1 (hCCS).''; PubMed Europe PMC Scholia
  51. Evrard C, Capron A, Marchand C, Clippe A, Wattiez R, Soumillion P, Knoops B, Declercq JP.; ''Crystal structure of a dimeric oxidized form of human peroxiredoxin 5.''; PubMed Europe PMC Scholia
  52. Culotta VC, Klomp LW, Strain J, Casareno RL, Krems B, Gitlin JD.; ''The copper chaperone for superoxide dismutase.''; PubMed Europe PMC Scholia
  53. Stasser JP, Eisses JF, Barry AN, Kaplan JH, Blackburn NJ.; ''Cysteine-to-serine mutants of the human copper chaperone for superoxide dismutase reveal a copper cluster at a domain III dimer interface.''; PubMed Europe PMC Scholia
  54. Gasdaska PY, Berggren MM, Berry MJ, Powis G.; ''Cloning, sequencing and functional expression of a novel human thioredoxin reductase.''; PubMed Europe PMC Scholia
  55. Knoops B, Clippe A, Bogard C, Arsalane K, Wattiez R, Hermans C, Duconseille E, Falmagne P, Bernard A.; ''Cloning and characterization of AOEB166, a novel mammalian antioxidant enzyme of the peroxiredoxin family.''; PubMed Europe PMC Scholia
  56. Ralat LA, Manevich Y, Fisher AB, Colman RF.; ''Direct evidence for the formation of a complex between 1-cysteine peroxiredoxin and glutathione S-transferase pi with activity changes in both enzymes.''; PubMed Europe PMC Scholia
  57. Murphy MP.; ''How mitochondria produce reactive oxygen species.''; PubMed Europe PMC Scholia
  58. Kienhöfer J, Häussler DJ, Ruckelshausen F, Muessig E, Weber K, Pimentel D, Ullrich V, Bürkle A, Bachschmid MM.; ''Association of mitochondrial antioxidant enzymes with mitochondrial DNA as integral nucleoid constituents.''; PubMed Europe PMC Scholia
  59. Nguyen VD, Saaranen MJ, Karala AR, Lappi AK, Wang L, Raykhel IB, Alanen HI, Salo KE, Wang CC, Ruddock LW.; ''Two endoplasmic reticulum PDI peroxidases increase the efficiency of the use of peroxide during disulfide bond formation.''; PubMed Europe PMC Scholia
  60. Ralat LA, Misquitta SA, Manevich Y, Fisher AB, Colman RF.; ''Characterization of the complex of glutathione S-transferase pi and 1-cysteine peroxiredoxin.''; PubMed Europe PMC Scholia
  61. Thorne NM, Hankin S, Wilkinson MC, Nuñez C, Barraclough R, McLennan AG.; ''Human diadenosine 5',5"'-P1,P4-tetraphosphate pyrophosphohydrolase is a member of the MutT family of nucleotide pyrophosphatases.''; PubMed Europe PMC Scholia
  62. Berkholz DS, Faber HR, Savvides SN, Karplus PA.; ''Catalytic cycle of human glutathione reductase near 1 A resolution.''; PubMed Europe PMC Scholia
  63. Wegerich F, Giachetti A, Allegrozzi M, Lisdat F, Turano P.; ''Mechanistic insights into the superoxide-cytochrome c reaction by lysine surface scanning.''; PubMed Europe PMC Scholia
  64. Marklund SL.; ''Human copper-containing superoxide dismutase of high molecular weight.''; PubMed Europe PMC Scholia
  65. Wernimont AK, Huffman DL, Lamb AL, O'Halloran TV, Rosenzweig AC.; ''Structural basis for copper transfer by the metallochaperone for the Menkes/Wilson disease proteins.''; PubMed Europe PMC Scholia
  66. Casareno RL, Waggoner D, Gitlin JD.; ''The copper chaperone CCS directly interacts with copper/zinc superoxide dismutase.''; PubMed Europe PMC Scholia
  67. Takahashi K, Newburger PE, Cohen HJ.; ''Glutathione peroxidase protein. Absence in selenium deficiency states and correlation with enzymatic activity.''; PubMed Europe PMC Scholia
  68. Marchissio MJ, Francés DE, Carnovale CE, Marinelli RA.; ''Mitochondrial aquaporin-8 knockdown in human hepatoma HepG2 cells causes ROS-induced mitochondrial depolarization and loss of viability.''; PubMed Europe PMC Scholia
  69. Muller FL, Liu Y, Van Remmen H.; ''Complex III releases superoxide to both sides of the inner mitochondrial membrane.''; PubMed Europe PMC Scholia
  70. Legault J, Carrier C, Petrov P, Renard P, Remacle J, Mirault ME.; ''Mitochondrial GPx1 decreases induced but not basal oxidative damage to mtDNA in T47D cells.''; PubMed Europe PMC Scholia
  71. Antunes F, Han D, Cadenas E.; ''Relative contributions of heart mitochondria glutathione peroxidase and catalase to H(2)O(2) detoxification in in vivo conditions.''; PubMed Europe PMC Scholia
  72. Fukai T, Ushio-Fukai M.; ''Superoxide dismutases: role in redox signaling, vascular function, and diseases.''; PubMed Europe PMC Scholia
  73. Rhee HW, Zou P, Udeshi ND, Martell JD, Mootha VK, Carr SA, Ting AY.; ''Proteomic mapping of mitochondria in living cells via spatially restricted enzymatic tagging.''; PubMed Europe PMC Scholia
  74. Wei PC, Hsieh YH, Su MI, Jiang X, Hsu PH, Lo WT, Weng JY, Jeng YM, Wang JM, Chen PL, Chang YC, Lee KF, Tsai MD, Shew JY, Lee WH.; ''Loss of the oxidative stress sensor NPGPx compromises GRP78 chaperone activity and induces systemic disease.''; PubMed Europe PMC Scholia
  75. Cho CS, Lee S, Lee GT, Woo HA, Choi EJ, Rhee SG.; ''Irreversible inactivation of glutathione peroxidase 1 and reversible inactivation of peroxiredoxin II by H2O2 in red blood cells.''; PubMed Europe PMC Scholia
  76. Karlsson K, Edlund A, Sandström J, Marklund SL.; ''Proteolytic modification of the heparin-binding affinity of extracellular superoxide dismutase.''; PubMed Europe PMC Scholia
  77. Kawamata H, Manfredi G.; ''Different regulation of wild-type and mutant Cu,Zn superoxide dismutase localization in mammalian mitochondria.''; PubMed Europe PMC Scholia
  78. Leitch JM, Jensen LT, Bouldin SD, Outten CE, Hart PJ, Culotta VC.; ''Activation of Cu,Zn-superoxide dismutase in the absence of oxygen and the copper chaperone CCS.''; PubMed Europe PMC Scholia
  79. Zielonka J, Sikora A, Joseph J, Kalyanaraman B.; ''Peroxynitrite is the major species formed from different flux ratios of co-generated nitric oxide and superoxide: direct reaction with boronate-based fluorescent probe.''; PubMed Europe PMC Scholia
  80. Ray PD, Huang BW, Tsuji Y.; ''Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling.''; PubMed Europe PMC Scholia
  81. He C, Murthy S, McCormick ML, Spitz DR, Ryan AJ, Carter AB.; ''Mitochondrial Cu,Zn-superoxide dismutase mediates pulmonary fibrosis by augmenting H2O2 generation.''; PubMed Europe PMC Scholia
  82. Hartz JW, Deutsch HF.; ''Subunit structure of human superoxide dismutase.''; PubMed Europe PMC Scholia
  83. Loos H, Roos D, Weening R, Houwerzijl J.; ''Familial deficiency of glutathione reductase in human blood cells.''; PubMed Europe PMC Scholia
  84. Hsu JL, Hsieh Y, Tu C, O'Connor D, Nick HS, Silverman DN.; ''Catalytic properties of human manganese superoxide dismutase.''; PubMed Europe PMC Scholia
  85. SCOTT EM, DUNCAN IW, EKSTRAND V.; ''PURIFICATION AND PROPERTIES OF GLUTATHIONE REDUCTASE OF HUMAN ERYTHROCYTES.''; PubMed Europe PMC Scholia
  86. Chu FF, Doroshow JH, Esworthy RS.; ''Expression, characterization, and tissue distribution of a new cellular selenium-dependent glutathione peroxidase, GSHPx-GI.''; PubMed Europe PMC Scholia
  87. Higgins CM, Jung C, Ding H, Xu Z.; ''Mutant Cu, Zn superoxide dismutase that causes motoneuron degeneration is present in mitochondria in the CNS.''; PubMed Europe PMC Scholia
  88. Hartman JR, Geller T, Yavin Z, Bartfeld D, Kanner D, Aviv H, Gorecki M.; ''High-level expression of enzymatically active human Cu/Zn superoxide dismutase in Escherichia coli.''; PubMed Europe PMC Scholia
  89. Kawamata H, Manfredi G.; ''Import, maturation, and function of SOD1 and its copper chaperone CCS in the mitochondrial intermembrane space.''; PubMed Europe PMC Scholia
  90. Sugiura M, Adachi T, Inoue H, Ito Y, Hirano K.; ''Purification and properties of two superoxide dismutases from human placenta.''; PubMed Europe PMC Scholia
  91. Wispé JR, Clark JC, Burhans MS, Kropp KE, Korfhagen TR, Whitsett JA.; ''Synthesis and processing of the precursor for human mangano-superoxide dismutase.''; PubMed Europe PMC Scholia
  92. Hall L, Williams K, Perry AC, Frayne J, Jury JA.; ''The majority of human glutathione peroxidase type 5 (GPX5) transcripts are incorrectly spliced: implications for the role of GPX5 in the male reproductive tract.''; PubMed Europe PMC Scholia
  93. Presnell CE, Bhatti G, Numan LS, Lerche M, Alkhateeb SK, Ghalib M, Shammaa M, Kavdia M.; ''Computational insights into the role of glutathione in oxidative stress.''; PubMed Europe PMC Scholia
  94. Dubuisson M, Vander Stricht D, Clippe A, Etienne F, Nauser T, Kissner R, Koppenol WH, Rees JF, Knoops B.; ''Human peroxiredoxin 5 is a peroxynitrite reductase.''; PubMed Europe PMC Scholia
  95. Putnam CD, Arvai AS, Bourne Y, Tainer JA.; ''Active and inhibited human catalase structures: ligand and NADPH binding and catalytic mechanism.''; PubMed Europe PMC Scholia
  96. Marklund SL, Holme E, Hellner L.; ''Superoxide dismutase in extracellular fluids.''; PubMed Europe PMC Scholia
  97. Butler J, Jayson GG, Swallow AJ.; ''The reaction between the superoxide anion radical and cytochrome c.''; PubMed Europe PMC Scholia
  98. Butler J, Koppenol WH, Margoliash E.; ''Kinetics and mechanism of the reduction of ferricytochrome c by the superoxide anion.''; PubMed Europe PMC Scholia
  99. Declercq JP, Evrard C, Clippe A, Stricht DV, Bernard A, Knoops B.; ''Crystal structure of human peroxiredoxin 5, a novel type of mammalian peroxiredoxin at 1.5 A resolution.''; PubMed Europe PMC Scholia
  100. Brown NM, Torres AS, Doan PE, O'Halloran TV.; ''Oxygen and the copper chaperone CCS regulate posttranslational activation of Cu,Zn superoxide dismutase.''; PubMed Europe PMC Scholia
  101. Radi R, Cassina A, Hodara R, Quijano C, Castro L.; ''Peroxynitrite reactions and formation in mitochondria.''; PubMed Europe PMC Scholia
  102. Brand MD.; ''The sites and topology of mitochondrial superoxide production.''; PubMed Europe PMC Scholia
  103. Swarbrick JD, Buyya S, Gunawardana D, Gayler KR, McLennan AG, Gooley PR.; ''Structure and substrate-binding mechanism of human Ap4A hydrolase.''; PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
117697view12:20, 22 May 2021EweitzModified title
114852view16:35, 25 January 2021ReactomeTeamReactome version 75
113298view11:36, 2 November 2020ReactomeTeamReactome version 74
112510view15:47, 9 October 2020ReactomeTeamReactome version 73
101422view11:30, 1 November 2018ReactomeTeamreactome version 66
100960view21:07, 31 October 2018ReactomeTeamreactome version 65
100497view19:41, 31 October 2018ReactomeTeamreactome version 64
100042view16:24, 31 October 2018ReactomeTeamreactome version 63
99595view14:58, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99213view12:43, 31 October 2018ReactomeTeamreactome version 62
93829view13:39, 16 August 2017ReactomeTeamreactome version 61
93380view11:22, 9 August 2017ReactomeTeamreactome version 61
87468view14:17, 22 July 2016MkutmonOntology Term : 'stress response pathway' added !
86467view09:18, 11 July 2016ReactomeTeamreactome version 56
83117view10:01, 18 November 2015ReactomeTeamVersion54
81457view12:59, 21 August 2015ReactomeTeamVersion53
76144view16:05, 11 June 2014AnweshaNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
2xHC-SOD1 ProteinP00441 (Uniprot-TrEMBL)
2xHC-TXN2ProteinQ99757 (Uniprot-TrEMBL)
2xHC-TXNProteinP10599 (Uniprot-TrEMBL)
ADPMetaboliteCHEBI:16761 (ChEBI)
AQP8 ProteinO94778 (Uniprot-TrEMBL)
AQP8 tetramerComplexR-HSA-3779353 (Reactome)
ATOX1 ProteinO00244 (Uniprot-TrEMBL)
ATOX1:Cu1+ComplexR-HSA-3697875 (Reactome)
ATOX1ProteinO00244 (Uniprot-TrEMBL)
ATP7AProteinQ04656 (Uniprot-TrEMBL)
ATPMetaboliteCHEBI:15422 (ChEBI)
CAT ProteinP04040 (Uniprot-TrEMBL)
CAT tetramerComplexR-HSA-76028 (Reactome)
CCS ProteinO14618 (Uniprot-TrEMBL)
CCS dimerComplexR-HSA-3299731 (Reactome)
CCS dimerComplexR-HSA-3780978 (Reactome)
CCS:Cu1+ dimerComplexR-HSA-3697845 (Reactome)
CCS:Cu1+ dimerComplexR-HSA-3780985 (Reactome)
CCS:SOD1 dimerComplexR-HSA-3780962 (Reactome)
CCS:SOD1ComplexR-HSA-3299706 (Reactome)
CYBA ProteinP13498 (Uniprot-TrEMBL)
CYBB ProteinP04839 (Uniprot-TrEMBL)
CYCS ProteinP99999 (Uniprot-TrEMBL)
Cu1+ MetaboliteCHEBI:49552 (ChEBI)
Cu2+ MetaboliteCHEBI:29036 (ChEBI)
Cytochrome c (oxidised)ComplexR-HSA-352607 (Reactome)
Cytochrome c (reduced)ComplexR-HSA-352609 (Reactome)
ERO1L ProteinQ96HE7 (Uniprot-TrEMBL)
ERO1L:GPX7,8ComplexR-HSA-3341375 (Reactome)
FAD MetaboliteCHEBI:16238 (ChEBI)
GMPMetaboliteCHEBI:17345 (ChEBI)
GP4GMetaboliteCHEBI:15883 (ChEBI)
GPX1 tetramerComplexR-HSA-3323016 (Reactome)
GPX1 tetramerComplexR-HSA-71674 (Reactome)
GPX2 ProteinP18283 (Uniprot-TrEMBL)
GPX2 tetramerComplexR-HSA-2142735 (Reactome)
GPX3 tetramerComplexR-HSA-3341349 (Reactome)
GPX5 ProteinO75715 (Uniprot-TrEMBL)
GPX5, (GPX6)ComplexR-HSA-6800144 (Reactome)
GPX6 ProteinP59796 (Uniprot-TrEMBL)
GPX7 ProteinQ96SL4 (Uniprot-TrEMBL)
GPX8 ProteinQ8TED1 (Uniprot-TrEMBL)
GSHMetaboliteCHEBI:16856 (ChEBI)
GSR dimerComplexR-HSA-3323075 (Reactome)
GSR-1 ProteinP00390-1 (Uniprot-TrEMBL)
GSR-2 ProteinP00390-2 (Uniprot-TrEMBL)
GSR-2:FAD dimerComplexR-HSA-71680 (Reactome)
GSSGMetaboliteCHEBI:17858 (ChEBI)
GSTP1 ProteinP09211 (Uniprot-TrEMBL)
GTPMetaboliteCHEBI:15996 (ChEBI)
H+MetaboliteCHEBI:15378 (ChEBI)
H2O2MetaboliteCHEBI:16240 (ChEBI)
H2OMetaboliteCHEBI:15377 (ChEBI)
HC53,56-P4HBProteinP07237 (Uniprot-TrEMBL)
L-selenoC49-GPX1 ProteinP07203 (Uniprot-TrEMBL)
L-selenoC73-GPX3 ProteinP22352 (Uniprot-TrEMBL)
L-selenocysteine residue-GPX1 ProteinP07203 (Uniprot-TrEMBL)
Mn2+ MetaboliteCHEBI:29035 (ChEBI)
NAD+MetaboliteCHEBI:15846 (ChEBI)
NADP+MetaboliteCHEBI:18009 (ChEBI)
NADPH MetaboliteCHEBI:16474 (ChEBI)
NADPHMetaboliteCHEBI:16474 (ChEBI)
NOMetaboliteCHEBI:16480 (ChEBI)
NOX4 ProteinQ9NPH5 (Uniprot-TrEMBL)
NOX4, NOX5ComplexR-HSA-6809211 (Reactome)
NOX5 ProteinQ96PH1 (Uniprot-TrEMBL)
NUDT2ProteinP50583 (Uniprot-TrEMBL)
NitriteMetaboliteCHEBI:16301 (ChEBI)
O2-MetaboliteCHEBI:18421 (ChEBI)
O2.-MetaboliteCHEBI:18421 (ChEBI)
O2MetaboliteCHEBI:15379 (ChEBI)
P4HBProteinP07237 (Uniprot-TrEMBL)
PRDX1 ProteinQ06830 (Uniprot-TrEMBL)
PRDX1,2,5ComplexR-HSA-3341359 (Reactome)
PRDX2 ProteinP32119 (Uniprot-TrEMBL)
PRDX3 ProteinP30048 (Uniprot-TrEMBL)
PRDX3,5ComplexR-HSA-3323011 (Reactome)
PRDX5 ProteinP30044-2 (Uniprot-TrEMBL)
PRDX5-1 ProteinP30044-1 (Uniprot-TrEMBL)
PRDX5-1ProteinP30044-1 (Uniprot-TrEMBL)
PRDX5ProteinP30044-2 (Uniprot-TrEMBL)
PRDX6 ProteinP30041 (Uniprot-TrEMBL)
PRDX6:GSTP1ComplexR-HSA-3343687 (Reactome)
PeroxynitriteMetaboliteCHEBI:25941 (ChEBI)
PiMetaboliteCHEBI:18367 (ChEBI)
SOD1 ProteinP00441 (Uniprot-TrEMBL)
SOD1 dimerComplexR-HSA-3299679 (Reactome)
SOD1 dimerComplexR-HSA-3777109 (Reactome)
SOD1:Zn2+ComplexR-HSA-3780986 (Reactome)
SOD1ProteinP00441 (Uniprot-TrEMBL)
SOD2 ProteinP04179 (Uniprot-TrEMBL)
SOD2 tetramerComplexR-HSA-3299689 (Reactome)
SOD3 (19-227) ProteinP08294 (Uniprot-TrEMBL)
SOD3 ProteinP08294 (Uniprot-TrEMBL)
SOD3 tetramerComplexR-HSA-3299688 (Reactome)
SOD3 tetramerComplexR-HSA-3697840 (Reactome)
SOD3ProteinP08294 (Uniprot-TrEMBL)
TNXRD1:FAD dimerComplexR-HSA-73532 (Reactome)
TXN2ProteinQ99757 (Uniprot-TrEMBL)
TXNProteinP10599 (Uniprot-TrEMBL)
TXNRD1 ProteinQ16881 (Uniprot-TrEMBL)
TXNRD2 ProteinQ9NNW7 (Uniprot-TrEMBL)
TXNRD2 dimerComplexR-HSA-3323058 (Reactome)
Zn2+ MetaboliteCHEBI:29105 (ChEBI)
Zn2+MetaboliteCHEBI:29105 (ChEBI)
ferriheme MetaboliteCHEBI:38574 (ChEBI)
ferroheme MetaboliteCHEBI:38573 (ChEBI)
heme MetaboliteCHEBI:17627 (ChEBI)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
2xHC-TXN2ArrowR-HSA-3322995 (Reactome)
2xHC-TXN2ArrowR-HSA-3697894 (Reactome)
2xHC-TXN2R-HSA-3323050 (Reactome)
2xHC-TXNArrowR-HSA-3341343 (Reactome)
2xHC-TXNArrowR-HSA-3697882 (Reactome)
2xHC-TXNR-HSA-73646 (Reactome)
ADPArrowR-HSA-3697838 (Reactome)
AQP8 tetramermim-catalysisR-HSA-3779381 (Reactome)
ATOX1:Cu1+R-HSA-3697838 (Reactome)
ATOX1ArrowR-HSA-3697838 (Reactome)
ATP7Amim-catalysisR-HSA-3697838 (Reactome)
ATPR-HSA-3697838 (Reactome)
CAT tetramermim-catalysisR-HSA-76031 (Reactome)
CCS dimerArrowR-HSA-3299753 (Reactome)
CCS dimerArrowR-HSA-3780979 (Reactome)
CCS:Cu1+ dimerR-HSA-3697860 (Reactome)
CCS:Cu1+ dimerR-HSA-3780958 (Reactome)
CCS:SOD1 dimerArrowR-HSA-3780958 (Reactome)
CCS:SOD1 dimerR-HSA-3780979 (Reactome)
CCS:SOD1ArrowR-HSA-3697860 (Reactome)
CCS:SOD1R-HSA-3299753 (Reactome)
CCS:SOD1mim-catalysisR-HSA-3299753 (Reactome)
Cytochrome c (oxidised)R-HSA-3341294 (Reactome)
Cytochrome c (reduced)ArrowR-HSA-3341294 (Reactome)
ERO1L:GPX7,8mim-catalysisR-HSA-3341296 (Reactome)
GMPArrowR-HSA-5696197 (Reactome)
GP4GR-HSA-5696197 (Reactome)
GPX1 tetramermim-catalysisR-HSA-3323013 (Reactome)
GPX1 tetramermim-catalysisR-HSA-71676 (Reactome)
GPX2 tetramermim-catalysisR-HSA-3341277 (Reactome)
GPX3 tetramermim-catalysisR-HSA-3341397 (Reactome)
GPX5, (GPX6)mim-catalysisR-HSA-6799695 (Reactome)
GSHArrowR-HSA-3323079 (Reactome)
GSHArrowR-HSA-71682 (Reactome)
GSHR-HSA-3323013 (Reactome)
GSHR-HSA-3341277 (Reactome)
GSHR-HSA-3341397 (Reactome)
GSHR-HSA-3343700 (Reactome)
GSHR-HSA-6799695 (Reactome)
GSHR-HSA-71676 (Reactome)
GSR dimermim-catalysisR-HSA-3323079 (Reactome)
GSR-2:FAD dimermim-catalysisR-HSA-71682 (Reactome)
GSSGArrowR-HSA-3323013 (Reactome)
GSSGArrowR-HSA-3341277 (Reactome)
GSSGArrowR-HSA-3341397 (Reactome)
GSSGArrowR-HSA-3343700 (Reactome)
GSSGArrowR-HSA-6799695 (Reactome)
GSSGArrowR-HSA-71676 (Reactome)
GSSGR-HSA-3323079 (Reactome)
GSSGR-HSA-71682 (Reactome)
GTPArrowR-HSA-5696197 (Reactome)
H+ArrowR-HSA-6807557 (Reactome)
H+R-HSA-3299680 (Reactome)
H+R-HSA-3299682 (Reactome)
H+R-HSA-3299691 (Reactome)
H+R-HSA-3323050 (Reactome)
H+R-HSA-3323079 (Reactome)
H+R-HSA-3777112 (Reactome)
H+R-HSA-71682 (Reactome)
H+R-HSA-73646 (Reactome)
H2O2ArrowR-HSA-3299680 (Reactome)
H2O2ArrowR-HSA-3299682 (Reactome)
H2O2ArrowR-HSA-3299691 (Reactome)
H2O2ArrowR-HSA-3777112 (Reactome)
H2O2ArrowR-HSA-3779381 (Reactome)
H2O2R-HSA-3322995 (Reactome)
H2O2R-HSA-3323013 (Reactome)
H2O2R-HSA-3341277 (Reactome)
H2O2R-HSA-3341296 (Reactome)
H2O2R-HSA-3341343 (Reactome)
H2O2R-HSA-3341397 (Reactome)
H2O2R-HSA-3343700 (Reactome)
H2O2R-HSA-3779381 (Reactome)
H2O2R-HSA-6799695 (Reactome)
H2O2R-HSA-71676 (Reactome)
H2O2R-HSA-76031 (Reactome)
H2OArrowR-HSA-3322995 (Reactome)
H2OArrowR-HSA-3323013 (Reactome)
H2OArrowR-HSA-3341277 (Reactome)
H2OArrowR-HSA-3341296 (Reactome)
H2OArrowR-HSA-3341343 (Reactome)
H2OArrowR-HSA-3341397 (Reactome)
H2OArrowR-HSA-3343700 (Reactome)
H2OArrowR-HSA-3697882 (Reactome)
H2OArrowR-HSA-3697894 (Reactome)
H2OArrowR-HSA-6799695 (Reactome)
H2OArrowR-HSA-71676 (Reactome)
H2OArrowR-HSA-76031 (Reactome)
H2OR-HSA-3697838 (Reactome)
H2OR-HSA-5696197 (Reactome)
HC53,56-P4HBArrowR-HSA-3341296 (Reactome)
NADP+ArrowR-HSA-3323050 (Reactome)
NADP+ArrowR-HSA-3323079 (Reactome)
NADP+ArrowR-HSA-6807557 (Reactome)
NADP+ArrowR-HSA-71682 (Reactome)
NADP+ArrowR-HSA-73646 (Reactome)
NADPHR-HSA-3323050 (Reactome)
NADPHR-HSA-3323079 (Reactome)
NADPHR-HSA-6807557 (Reactome)
NADPHR-HSA-71682 (Reactome)
NADPHR-HSA-73646 (Reactome)
NOR-HSA-1222407 (Reactome)
NOR-HSA-3697855 (Reactome)
NOX4, NOX5mim-catalysisR-HSA-6807557 (Reactome)
NUDT2mim-catalysisR-HSA-5696197 (Reactome)
NitriteArrowR-HSA-3697882 (Reactome)
NitriteArrowR-HSA-3697894 (Reactome)
O2-R-HSA-3341294 (Reactome)
O2-R-HSA-3777112 (Reactome)
O2.-ArrowR-HSA-6807557 (Reactome)
O2.-R-HSA-1222407 (Reactome)
O2.-R-HSA-3299680 (Reactome)
O2.-R-HSA-3299682 (Reactome)
O2.-R-HSA-3299691 (Reactome)
O2.-R-HSA-3697855 (Reactome)
O2ArrowR-HSA-3299680 (Reactome)
O2ArrowR-HSA-3299682 (Reactome)
O2ArrowR-HSA-3299691 (Reactome)
O2ArrowR-HSA-3341294 (Reactome)
O2ArrowR-HSA-3777112 (Reactome)
O2ArrowR-HSA-76031 (Reactome)
O2R-HSA-6807557 (Reactome)
P4HBR-HSA-3341296 (Reactome)
PRDX1,2,5mim-catalysisR-HSA-3341343 (Reactome)
PRDX3,5mim-catalysisR-HSA-3322995 (Reactome)
PRDX5-1mim-catalysisR-HSA-3697894 (Reactome)
PRDX5mim-catalysisR-HSA-3697882 (Reactome)
PRDX6:GSTP1mim-catalysisR-HSA-3343700 (Reactome)
PeroxynitriteArrowR-HSA-1222407 (Reactome)
PeroxynitriteArrowR-HSA-3697855 (Reactome)
PeroxynitriteR-HSA-3697882 (Reactome)
PeroxynitriteR-HSA-3697894 (Reactome)
PiArrowR-HSA-3697838 (Reactome)
R-HSA-1222407 (Reactome) Nitric oxide and superoxide rapidly combine to form peroxynitrite (Pryor & Squadrito 1995).
R-HSA-3299680 (Reactome) Mn superoxide dismutase (SOD2) is located in the mitochondrial matrix where it catalyzes the reaction of two molecules of superoxide (O2-.) to form one molecule of oxygen (O2) and one molecule of hydrogen peroxide (H2O2). Data from mouse liver indicate that respiratory complex I leaks superoxide into the matrix and respiratory complex III leaks superoxide into both the matrix and the intermembrane space (Muller et al. 2004). Because of its negative charge superoxide is unable to cross membranes, however hydrogen peroxide, a product of SOD2, is released from mitochondria to the cytosol in proportion to the proton potential (inferred from rat heart mitochondria in Boveris et al. 2006, Korshunov et al. 1997).
R-HSA-3299682 (Reactome) Extracellular Cu-Zn superoxide dismutase (SOD3) catalyzes the reaction of two molecules of superoxide (O2.-) to form one molecule of oxygen (O2) and one molecule of hydrogen peroxide (H2O2) (Marklund et al. 1982, Marklund 1982)
R-HSA-3299691 (Reactome) Cu-Zn superoxide dismutase (SOD1), originally known as erythrocuprein, catalyzes the reaction of two molecules of superoxide (O2.-) to yield one molecule of hydrogen peroxide (H2O2) and one molecule of oxygen (O2) (McCord and Fridovich 1969 assayed both bovine and human Cu-Zn superoxide dismutase, the human sample provided by Carrico and Deutsch). Diffusion of hydrogen peroxide, the product of SOD1, across the cytosol is limited (Mishina et al. 2011)
R-HSA-3299753 (Reactome) Copper chaperone of superoxide dismutase (CCS) transfers a copper(I) atom to a SOD1 monomer that already contains a Zn atom. After initial heterodimerization between SOD1 and CCS, the copper atom is transferred, intramolecular cysteine disulfide bonds are formed in SOD1, and SOD1 dimerizes (Banci et al. 2012, Casareno et al. 1998, Culotta et al. 1997, Rae et al. 2001, Brown et al. 2004, Carroll et al. 2006, Kawamata and Manfredi 2008). The transfer of copper to SOD1 requires oxygen but it is unknown at which step the oxygen acts (Brown et al. 2004). There is also a CCS-independent, oxygen-independent pathway of maturation of SOD1 (Leitch et al. 2009) whose molecular details and physiological role are not well characterized.
R-HSA-3322995 (Reactome) Peroxiredoxin 3 (PRDX3) and PRDX5 in the mitochondrial matrix reduce hydrogen peroxide (H2O2) with thioredoxin to yield oxidized thioredoxin and water (Yamashita et al. 1999, Knoops et al. 1999, Cao et al. 2007, Nagy et al. 2011). Reduced PRDX5 is a monomer (Declercq et al. 2001) and oxidized PRDX5 is a dimer (Evrard et al. 2004) therefore the enzyme may cycle between states.
R-HSA-3323013 (Reactome) Glutathione peroxidase 1 (GPX1) located in the mitochondrial matrix uses glutathione to reduce hydrogen peroxide (H2O2) to yield oxidized glutathione and water (Legault et al. 2000, Li et al. 2000, Faucher et al. 2003). As inferred from rat mitochondria, GPX1 is the major determinant of steady-state hydrogen peroxide levels (Antunes et al. 2002).
R-HSA-3323050 (Reactome) Thioredoxin reductase 2 (TXNRD2) in the mitochondrial matrix regenerates reduced thioredoxin (TXN) by reacting oxidized thioredoxin with NADPH (Gasdaska et al. 1999, Cao et al. 2007).
R-HSA-3323079 (Reactome) Glutathione reductase (GSR) in the mitochondrial matrix regenerates reduced glutathione from oxidized glutathione and NADPH (Berkholz et al. 2008).
R-HSA-3341277 (Reactome) GPX2 (located in the gastrointestinal tract, also called GSHPx-GI, GPX-GI, and GI-GPx), like glutathione peroxidase 1 (GPX1, ubiquitous), reduces one molecule of hydrogen peroxide (H2O2) with two molecules of glutathione to yield one molecule of oxidized glutathione (glutathione disulfide, GSSG) and two molecules of water (Chu et al. 1998).
R-HSA-3341294 (Reactome) Superoxide can reduce cytochrome c in the intermembrane space (Wegerich et al. 2013, and inferred from other mammals in Butler et al. 1975, Koppenol et al. 1976, Butler et al. 1982). Superoxide has been shown in rat and mouse mitochondria to be released into the intermembrane space by the complex III of the respiratory chain (Han et al. 2001, Muller et al. 2004).
R-HSA-3341296 (Reactome) Glutathione peroxidase 7 (GPX7) and GPX8 are atypical glutathione peroxidases that catalyze the peroxidation of protein disulfide isomerases, such as PDI (P4HB) (Nguyen et al. 2011 and inferred from mouse in Bosello-Travain et al. 2013). GPX7 and GPX8 are each able to form heterodimers with the sulfhydryl oxidase ERO1alpha (ERO1L) in the endoplasmic reticulum lumen. It is hypothesized that GPX7 and GPX8 use hydrogen peroxide produced by ERO1L.
R-HSA-3341343 (Reactome) Peroxiredoxin 1 (PRDX1), PRDX2, and PRDX5 in the cytosol reduce hydrogen peroxide (H2O2) with thioredoxin yielding oxidized thioredoxin and water (Yamashita et al. 1999, Lee et al. 2007, Nagy et al. 2011).
R-HSA-3341397 (Reactome) Glutathione peroxidase 3 (GPX3) in plasma reduces hydrogen peroxide (H2O2) with glutathione to yield oxidized glutathione and water (Maddipati and Marnett 1987, Takahashi et al. 1987, Chung et al. 2009, Ottaviano et al. 2009). Glutathione is synthesized in the liver and exported into the plasma.
R-HSA-3343700 (Reactome) Peroxiredoxin 6 (PRDX6) forms a heterodimer with GSTP1 (Pi Glutathione transferase) and catalyzes the reduction of hydrogen peroxide (H2O2) by glutathione to yield oxidized glutathione and water (Ralat et al. 2006, Ralat et al. 2008, Zhou et al. 2013).
R-HSA-3697838 (Reactome) As inferred from mouse, ATP7A (Menke's ATPase, MNK) transports copper from ATOX in the cytosol to SOD3 in the lumen of the trans golgi network. ATP7A and SOD3 directly interact. Mutations in ATP7A cause Menke's disease, a neurodegenerative condition.
R-HSA-3697855 (Reactome) Superoxide and nitric oxide react to form peroxynitrite within mitochondria (Huie and Padmaja 1993, Packer et al. 1996, reviewed in Radi et al. 2002).
R-HSA-3697860 (Reactome) Copper chaperone of superoxide dismutase (CCS) transfers a copper(I) atom to a SOD1 monomer that already contains a Zn atom (Culotta et al. 1997, Casareno et al. 1998, Rae et al. 2001, Brown et al. 2004, Banci et al. 2012). The reaction proceeds by a two step mechanism in which SOD1 first forms heterodimers with CCS (Rae et al. 2001, Banci et al. 2012).
R-HSA-3697882 (Reactome) Peroxiredoxin 5 (PRDX5) very efficiently reduces peroxynitrite using thioredoxin to yield nitrite (NO2-), water, and oxidized thioredoxin (Dubuisson et al. 2004). The N-terminal cysteine (Cys 47) of PRDX5 attacks the O-O peroxide bond of peroxynitrite.
R-HSA-3697894 (Reactome) Peroxiredoxin 5 (PRDX5) very efficiently reduces peroxynitrite using TXN2 in mitochodria to yield nitrite (NO2-), water, and oxidized TXN2 (Dubuisson et al. 2004). The N-terminal cysteine (Cys 47) of PRDX5 attacks the O-O peroxide bond of peroxynitrite.
R-HSA-3777112 (Reactome) A portion of SOD1 is located in the mitochondrial intermembrane space (IMS) where it catalyzes the formation of oxygen (O2) and hydrogen peroxide (H2O2) from superoxide (O2.-) (He et al. 2011, Higgins et al. 2002, inferred from rat in Okado-Matsumoto and Fridovich 2001).
R-HSA-3779381 (Reactome) As inferred from rat heart mitochondria, hydrogen peroxide is released from mitochondria at a rate that is dependent on the membrane potential. Knockdown of Aquaporin-8 (AQP8) in human cells indicates that hydrogen peroxide is able to transit through the water channel of AQP8 located in the inner mitochodrial membrane (Marchissio et al. 2012). The resulting level of cytosolic hydrogen peroxide is hypothesized to signal the state of the mitochondria to regulatory molecules in the cytosol and nucleus (reviewed in Antico Arciuch et al. 2012).
R-HSA-3780958 (Reactome) As inferred from the cytosolic reaction and from the mouse mitochondrial reaction, Copper chaperone of superoxide dismutase (CCS) transfers a copper(I) atom to a SOD1 monomer that already contains a Zn atom. The reaction proceeds by a two step mechanism in which SOD1 first forms heterodimers with CCS. The amounts of CCS and SOD1 in the intermembrane space appear to be regulated by the concentration of oxygen. Mutations in SOD1 are responsible for familial amyotrophic lateral sclerosis (fALS) and cause unregulated localization and aggregation of SOD1 in the intermembrane space (reviewed in Kawamata and Manfredi 2010).
R-HSA-3780979 (Reactome) As inferred from the cytosolic reaction and from the mitochondrial reaction in mouse, Copper chaperone of superoxide dismutase (CCS) transfers a copper(I) atom to a SOD1 monomer that already contains a Zn atom. After initial heterodimerization between SOD1 and CCS, the copper atom is transferred, intramolecular cysteine disulfide bonds are formed in SOD1, and SOD1 dimerizes.
R-HSA-4837364 (Reactome) SOD3 is secreted from cells into the extracellular region. Before secretion a portion of SOD3 molecules are cleaved near the C-terminus at glutamate-227 (glutamate-209 in the mature protein) (Olsen et al. 2004, Karlsson et al. 1993). Removal of the C-terminus prevents interaction with the extracellular matrix so cleaved molecules are soluble. Cleaved and uncleaved molecules are believed to be capable of forming mixed tetramers (Sandstrom et al. 1993).
R-HSA-5696197 (Reactome) Bis(5'-nucleosyl)-tetraphosphatase (asymmetrical) (NUDT2) mediates the asymmetrical hydrolysis of P(1),P(4)-bis(5'-guanosyl) tetraphosphate (GP4G) to yield AMP and ATP. GP4G is implicated in the regulation of cellular responses to stress and its hydrolysis could serve as a mechanism by which homeostasis is maintained by preventing its build-up (Thorne et al. 1995, Swarbrick et al. 2005).
R-HSA-6799695 (Reactome) Epididymal secretory glutathione peroxidase (GPX5), a secreted and selenium-independent isoform of glutathione peroxidases, is present in very low levels in human sperm ejaculate. GPX5 has the potential to reduce hydrogen peroxide (H2O2) using glutathione (GSH), based on activity observed in rat and pig forms of the enzyme but its role in human epidydimis is unknown (Hall et al. 1998). Glutathione peroxidase 6 (GPX6) is thought to have peroxidase activity based on sequence similarity to GPX5.
R-HSA-6807557 (Reactome) NADPH oxidases 4 and 5 (NOX4, 5) are ER membrane-bound proteins that generates superoxide (O2.-) in endothelial cells (BelAiba et al. 2007). NOX4 functions in association with cytochrome b heterodimer (CYBA:CYBB) on the ER (and nuclear) membrane (Martyn et al. 2006).
R-HSA-71676 (Reactome) Cytosolic glutathione peroxidase (GPX1) tetramer catalyzes the reaction of reduced glutathione and hydrogen peroxide to form reduced glutathione and water (Chu et al. 1993).
R-HSA-71682 (Reactome) Cytosolic glutathione reductase catalyzes the reaction of glutathione (oxidized) and NADPH + H+ to form two molecules of glutathione (reduced) and NADP+ (Scott et al. 1963, Loos et al. 1976). Deficiency of glutathione reductase can cause hemolytic anemia.
R-HSA-73646 (Reactome) Cytosolic thioredoxin reductase catalyzes the reaction of thioredoxin, oxidized and NADPH + H+ to form thioredoxin, reduced and NADP+ (Urig et al. 2006).
R-HSA-76031 (Reactome) Hydrogen peroxide is generated in the course of peroxisomal fatty acid oxidation and purine catabolism, and is rapidly converted to water and molecular oxygen by the enzyme catalase. This enzyme is widely distributed in the body, but is especially abundant in liver, kidney, and red blood cells.
SOD1 dimerArrowR-HSA-3299753 (Reactome)
SOD1 dimerArrowR-HSA-3780979 (Reactome)
SOD1 dimermim-catalysisR-HSA-3299691 (Reactome)
SOD1 dimermim-catalysisR-HSA-3777112 (Reactome)
SOD1:Zn2+R-HSA-3780958 (Reactome)
SOD1R-HSA-3697860 (Reactome)
SOD2 tetramermim-catalysisR-HSA-3299680 (Reactome)
SOD3 tetramerArrowR-HSA-3697838 (Reactome)
SOD3 tetramerArrowR-HSA-4837364 (Reactome)
SOD3 tetramerR-HSA-4837364 (Reactome)
SOD3 tetramermim-catalysisR-HSA-3299682 (Reactome)
SOD3R-HSA-3697838 (Reactome)
TNXRD1:FAD dimermim-catalysisR-HSA-73646 (Reactome)
TXN2ArrowR-HSA-3323050 (Reactome)
TXN2R-HSA-3322995 (Reactome)
TXN2R-HSA-3697894 (Reactome)
TXNArrowR-HSA-73646 (Reactome)
TXNR-HSA-3341343 (Reactome)
TXNR-HSA-3697882 (Reactome)
TXNRD2 dimermim-catalysisR-HSA-3323050 (Reactome)
Zn2+R-HSA-3697838 (Reactome)
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