ENTRY       hsa00480                    Pathway
NAME        Glutathione metabolism - Homo sapiens (human)
CLASS       Metabolism; Metabolism of other amino acids
PATHWAY_MAP hsa00480  Glutathione metabolism
MODULE      hsa_M00118  Glutathione biosynthesis, glutamate => glutathione [PATH:hsa00480]
NETWORK     nt06026  Glutathione biosynthesis
  ELEMENT   N00899  Glutathione biosynthesis
            N00904  Glutathione reduction
            N00905  NADP+ reduction
DRUG        D00341  Hydroxyurea (USP)
            D00829  Eflornithine hydrochloride (USAN)
            D02755  Acivicin (USAN/INN)
            D07883  Eflornithine (INN)
            D08917  Ezatiostat hydrochloride (USAN)
DBLINKS     GO: 0006749
ORGANISM    Homo sapiens (human) [GN:hsa]
GENE        2686  GGT7; gamma-glutamyltransferase 7 [KO:K00681] [EC:2.3.2.2 3.4.19.13]
            124975  GGT6; gamma-glutamyltransferase 6 [KO:K00681] [EC:2.3.2.2 3.4.19.13]
            2678  GGT1; gamma-glutamyltransferase 1 [KO:K18592] [EC:2.3.2.2 3.4.19.13 3.4.19.14]
            2687  GGT5; gamma-glutamyltransferase 5 [KO:K18592] [EC:2.3.2.2 3.4.19.13 3.4.19.14]
            79017  GGCT; gamma-glutamylcyclotransferase [KO:K00682] [EC:4.3.2.9]
            79094  CHAC1; ChaC glutathione specific gamma-glutamylcyclotransferase 1 [KO:K07232] [EC:4.3.2.7]
            494143  CHAC2; ChaC glutathione specific gamma-glutamylcyclotransferase 2 [KO:K07232] [EC:4.3.2.7]
            26873  OPLAH; 5-oxoprolinase, ATP-hydrolysing [KO:K01469] [EC:3.5.2.9]
            2729  GCLC; glutamate-cysteine ligase catalytic subunit [KO:K11204] [EC:6.3.2.2]
            2730  GCLM; glutamate-cysteine ligase modifier subunit [KO:K11205]
            2937  GSS; glutathione synthetase [KO:K21456] [EC:6.3.2.3]
            51056  LAP3; leucine aminopeptidase 3 [KO:K11142] [EC:3.4.11.1 3.4.11.5]
            290  ANPEP; alanyl aminopeptidase, membrane [KO:K11140] [EC:3.4.11.2]
            221357  GSTA5; glutathione S-transferase alpha 5 [KO:K00799] [EC:2.5.1.18]
            2939  GSTA2; glutathione S-transferase alpha 2 [KO:K00799] [EC:2.5.1.18]
            2941  GSTA4; glutathione S-transferase alpha 4 [KO:K00799] [EC:2.5.1.18]
            119391  GSTO2; glutathione S-transferase omega 2 [KO:K00799] [EC:2.5.1.18]
            2948  GSTM4; glutathione S-transferase mu 4 [KO:K00799] [EC:2.5.1.18]
            2953  GSTT2; glutathione S-transferase theta 2 (gene/pseudogene) [KO:K00799] [EC:2.5.1.18]
            2952  GSTT1; glutathione S-transferase theta 1 [KO:K00799] [EC:2.5.1.18]
            2947  GSTM3; glutathione S-transferase mu 3 [KO:K00799] [EC:2.5.1.18]
            4257  MGST1; microsomal glutathione S-transferase 1 [KO:K00799] [EC:2.5.1.18]
            4259  MGST3; microsomal glutathione S-transferase 3 [KO:K00799] [EC:2.5.1.18]
            2944  GSTM1; glutathione S-transferase mu 1 [KO:K00799] [EC:2.5.1.18]
            2949  GSTM5; glutathione S-transferase mu 5 [KO:K00799] [EC:2.5.1.18]
            4258  MGST2; microsomal glutathione S-transferase 2 [KO:K00799] [EC:2.5.1.18]
            2938  GSTA1; glutathione S-transferase alpha 1 [KO:K00799] [EC:2.5.1.18]
            2946  GSTM2; glutathione S-transferase mu 2 [KO:K00799] [EC:2.5.1.18]
            2940  GSTA3; glutathione S-transferase alpha 3 [KO:K00799] [EC:2.5.1.18]
            9446  GSTO1; glutathione S-transferase omega 1 [KO:K00799] [EC:2.5.1.18]
            653689  GSTT2B; glutathione S-transferase theta 2B [KO:K00799] [EC:2.5.1.18]
            2950  GSTP1; glutathione S-transferase pi 1 [KO:K23790] [EC:2.5.1.18]
            373156  GSTK1; glutathione S-transferase kappa 1 [KO:K13299] [EC:2.5.1.18]
            27306  HPGDS; hematopoietic prostaglandin D synthase [KO:K04097] [EC:5.3.99.2 2.5.1.18]
            10314  LANCL1; LanC like glutathione S-transferase 1 [KO:K25210] [EC:2.5.1.18]
            9027  NAT8; N-acetyltransferase 8 (putative) [KO:K20838] [EC:2.3.1.80 2.3.1.-]
            2936  GSR; glutathione-disulfide reductase [KO:K00383] [EC:1.8.1.7]
            3417  IDH1; isocitrate dehydrogenase (NADP(+)) 1 [KO:K00031] [EC:1.1.1.42]
            3418  IDH2; isocitrate dehydrogenase (NADP(+)) 2 [KO:K00031] [EC:1.1.1.42]
            5226  PGD; phosphogluconate dehydrogenase [KO:K00033] [EC:1.1.1.44 1.1.1.343]
            2539  G6PD; glucose-6-phosphate dehydrogenase [KO:K00036] [EC:1.1.1.49 1.1.1.363]
            51060  TXNDC12; thioredoxin domain containing 12 [KO:K05360] [EC:1.8.4.2]
            2879  GPX4; glutathione peroxidase 4 [KO:K05361] [EC:1.11.1.12]
            257202  GPX6; glutathione peroxidase 6 [KO:K00432] [EC:1.11.1.9]
            2882  GPX7; glutathione peroxidase 7 [KO:K00432] [EC:1.11.1.9]
            2877  GPX2; glutathione peroxidase 2 [KO:K00432] [EC:1.11.1.9]
            2878  GPX3; glutathione peroxidase 3 [KO:K00432] [EC:1.11.1.9]
            2876  GPX1; glutathione peroxidase 1 [KO:K00432] [EC:1.11.1.9]
            2880  GPX5; glutathione peroxidase 5 [KO:K00432] [EC:1.11.1.9]
            493869  GPX8; glutathione peroxidase 8 (putative) [KO:K00432] [EC:1.11.1.9]
            9588  PRDX6; peroxiredoxin 6 [KO:K11188] [EC:1.11.1.7 1.11.1.27 3.1.1.-]
            4953  ODC1; ornithine decarboxylase 1 [KO:K01581] [EC:4.1.1.17]
            6723  SRM; spermidine synthase [KO:K00797] [EC:2.5.1.16]
            6611  SMS; spermine synthase [KO:K00802] [EC:2.5.1.22]
            6240  RRM1; ribonucleotide reductase catalytic subunit M1 [KO:K10807] [EC:1.17.4.1]
            50484  RRM2B; ribonucleotide reductase regulatory TP53 inducible subunit M2B [KO:K10808] [EC:1.17.4.1]
            6241  RRM2; ribonucleotide reductase regulatory subunit M2 [KO:K10808] [EC:1.17.4.1]
COMPOUND    C00005  NADPH
            C00006  NADP+
            C00024  Acetyl-CoA
            C00025  L-Glutamate
            C00037  Glycine
            C00051  Glutathione
            C00072  Ascorbate
            C00077  L-Ornithine
            C00097  L-Cysteine
            C00127  Glutathione disulfide
            C00134  Putrescine
            C00151  L-Amino acid
            C00315  Spermidine
            C00669  gamma-L-Glutamyl-L-cysteine
            C00750  Spermine
            C01322  RX
            C01419  Cys-Gly
            C01672  Cadaverine
            C01879  5-Oxoproline
            C02090  Trypanothione
            C02320  R-S-Glutathione
            C03170  Trypanothione disulfide
            C03646  Bis-gamma-glutamylcystine
            C03740  (5-L-Glutamyl)-L-amino acid
            C05422  Dehydroascorbate
            C05726  S-Substituted L-cysteine
            C05727  S-Substituted N-acetyl-L-cysteine
            C05729  R-S-Cysteinylglycine
            C05730  Glutathionylspermidine
            C16562  Glutathionylspermine
            C16563  Bis(glutathionyl)spermine
            C16564  Bis(glutathionyl)spermine disulfide
            C16565  Aminopropylcadaverine
            C16566  Glutathionylaminopropylcadaverine
            C16567  Homotrypanothione
            C16568  Homotrypanothione disulfide
            C16663  Tryparedoxin
            C16664  Tryparedoxin disulfide
REFERENCE   PMID:12675513
  AUTHORS   Josch C, Klotz LO, Sies H.
  TITLE     Identification of cytosolic leucyl aminopeptidase (EC 3.4.11.1) as the major cysteinylglycine-hydrolysing activity in rat liver.
  JOURNAL   Biol Chem 384:213-8 (2003)
            DOI:10.1515/BC.2003.023
REFERENCE   PMID:18482986
  AUTHORS   Chu L, Lai Y, Xu X, Eddy S, Yang S, Song L, Kolodrubetz D.
  TITLE     A 52-kDa leucyl aminopeptidase from treponema denticola is a cysteinylglycinase that mediates the second step of glutathione metabolism.
  JOURNAL   J Biol Chem 283:19351-8 (2008)
            DOI:10.1074/jbc.M801034200
REFERENCE   PMID:14583094
  AUTHORS   Cappiello M, Lazzarotti A, Buono F, Scaloni A, D'Ambrosio C, Amodeo P, Mendez BL, Pelosi P, Del Corso A, Mura U.
  TITLE     New role for leucyl aminopeptidase in glutathione turnover.
  JOURNAL   Biochem J 378:35-44 (2004)
            DOI:10.1042/BJ20031336
REFERENCE   PMID:11157967
  AUTHORS   Suzuki H, Kamatani S, Kim ES, Kumagai H.
  TITLE     Aminopeptidases A, B, and N and dipeptidase D are the four cysteinylglycinases of Escherichia coli K-12.
  JOURNAL   J Bacteriol 183:1489-90 (2001)
            DOI:10.1128/JB.183.4.1489-1490.2001
REFERENCE   PMID:15610825
  AUTHORS   Oza SL, Shaw MP, Wyllie S, Fairlamb AH.
  TITLE     Trypanothione biosynthesis in Leishmania major.
  JOURNAL   Mol Biochem Parasitol 139:107-16 (2005)
            DOI:10.1016/j.molbiopara.2004.10.004
REFERENCE   PMID:12049631
  AUTHORS   Oza SL, Ariyanayagam MR, Fairlamb AH.
  TITLE     Characterization of recombinant glutathionylspermidine synthetase/amidase from Crithidia fasciculata.
  JOURNAL   Biochem J 364:679-86 (2002)
            DOI:10.1042/BJ20011370
REFERENCE   PMID:9677355
  AUTHORS   Tetaud E, Manai F, Barrett MP, Nadeau K, Walsh CT, Fairlamb AH.
  TITLE     Cloning and characterization of the two enzymes responsible for trypanothione biosynthesis in Crithidia fasciculata.
  JOURNAL   J Biol Chem 273:19383-90 (1998)
            DOI:10.1074/jbc.273.31.19383
REFERENCE   PMID:12750367
  AUTHORS   Ariyanayagam MR, Oza SL, Mehlert A, Fairlamb AH.
  TITLE     Bis(glutathionyl)spermine and other novel trypanothione analogues in Trypanosoma cruzi.
  JOURNAL   J Biol Chem 278:27612-9 (2003)
            DOI:10.1074/jbc.M302750200
REFERENCE   PMID:12967709
  AUTHORS   Oza SL, Ariyanayagam MR, Aitcheson N, Fairlamb AH.
  TITLE     Properties of trypanothione synthetase from Trypanosoma brucei.
  JOURNAL   Mol Biochem Parasitol 131:25-33 (2003)
            DOI:10.1016/S0166-6851(03)00176-2
REFERENCE   PMID:12121990
  AUTHORS   Oza SL, Tetaud E, Ariyanayagam MR, Warnon SS, Fairlamb AH.
  TITLE     A single enzyme catalyses formation of Trypanothione from glutathione and spermidine in Trypanosoma cruzi.
  JOURNAL   J Biol Chem 277:35853-61 (2002)
            DOI:10.1074/jbc.M204403200
REFERENCE   PMID:15537651
  AUTHORS   Comini M, Menge U, Wissing J, Flohe L.
  TITLE     Trypanothione synthesis in crithidia revisited.
  JOURNAL   J Biol Chem 280:6850-60 (2005)
            DOI:10.1074/jbc.M404486200
REFERENCE   PMID:7813456
  AUTHORS   Hunter KJ, Le Quesne SA, Fairlamb AH.
  TITLE     Identification and biosynthesis of N1,N9-bis(glutathionyl)aminopropylcadaverine (homotrypanothione) in Trypanosoma cruzi.
  JOURNAL   Eur J Biochem 226:1019-27 (1994)
            DOI:10.1111/j.1432-1033.1994.t01-1-01019.x
REFERENCE   PMID:12751784
  AUTHORS   Krauth-Siegel RL, Meiering SK, Schmidt H.
  TITLE     The parasite-specific trypanothione metabolism of trypanosoma and leishmania.
  JOURNAL   Biol Chem 384:539-49 (2003)
            DOI:10.1515/BC.2003.062
REFERENCE   PMID:18395526
  AUTHORS   Krauth-Siegel RL, Comini MA.
  TITLE     Redox control in trypanosomatids, parasitic protozoa with trypanothione-based thiol metabolism.
  JOURNAL   Biochim Biophys Acta 1780:1236-48 (2008)
            DOI:10.1016/j.bbagen.2008.03.006
REFERENCE   PMID:8892297
  AUTHORS   Krauth-Siegel RL, Ludemann H.
  TITLE     Reduction of dehydroascorbate by trypanothione.
  JOURNAL   Mol Biochem Parasitol 80:203-8 (1996)
            DOI:10.1016/0166-6851(96)02689-8
REFERENCE   PMID:11150302
  AUTHORS   Dormeyer M, Reckenfelderbaumer N, Ludemann H, Krauth-Siegel RL.
  TITLE     Trypanothione-dependent synthesis of deoxyribonucleotides by Trypanosoma brucei ribonucleotide reductase.
  JOURNAL   J Biol Chem 276:10602-6 (2001)
            DOI:10.1074/jbc.M010352200
REFERENCE   PMID:12949079
  AUTHORS   Schmidt H, Krauth-Siegel RL.
  TITLE     Functional and physicochemical characterization of the thioredoxin system in Trypanosoma brucei.
  JOURNAL   J Biol Chem 278:46329-36 (2003)
            DOI:10.1074/jbc.M305338200
REFERENCE   PMID:9851611
  AUTHORS   Tetaud E, Fairlamb AH.
  TITLE     Cloning, expression and reconstitution of the trypanothione-dependent peroxidase system of Crithidia fasciculata.
  JOURNAL   Mol Biochem Parasitol 96:111-23 (1998)
            DOI:10.1016/S0166-6851(98)00120-0
REFERENCE   PMID:12446213
  AUTHORS   Castro H, Sousa C, Santos M, Cordeiro-da-Silva A, Flohe L, Tomas AM.
  TITLE     Complementary antioxidant defense by cytoplasmic and mitochondrial peroxiredoxins in Leishmania infantum.
  JOURNAL   Free Radic Biol Med 33:1552-62 (2002)
            DOI:10.1016/S0891-5849(02)01089-4
REFERENCE   PMID:10713147
  AUTHORS   Wilkinson SR, Temperton NJ, Mondragon A, Kelly JM.
  TITLE     Distinct mitochondrial and cytosolic enzymes mediate trypanothione-dependent peroxide metabolism in Trypanosoma cruzi.
  JOURNAL   J Biol Chem 275:8220-5 (2000)
            DOI:10.1074/jbc.275.11.8220
REFERENCE   PMID:17922848
  AUTHORS   Konig J, Fairlamb AH.
  TITLE     A comparative study of type I and type II tryparedoxin peroxidases in Leishmania major.
  JOURNAL   FEBS J 274:5643-58 (2007)
            DOI:10.1111/j.1742-4658.2007.06087.x
REFERENCE   PMID:12466271
  AUTHORS   Hillebrand H, Schmidt A, Krauth-Siegel RL.
  TITLE     A second class of peroxidases linked to the trypanothione metabolism.
  JOURNAL   J Biol Chem 278:6809-15 (2003)
            DOI:10.1074/jbc.M210392200
REFERENCE   PMID:14982633
  AUTHORS   Soksawatmaekhin W, Kuraishi A, Sakata K, Kashiwagi K, Igarashi K.
  TITLE     Excretion and uptake of cadaverine by CadB and its physiological functions in Escherichia coli.
  JOURNAL   Mol Microbiol 51:1401-12 (2004)
            DOI:10.1046/j.1365-2958.2003.03913.x
REFERENCE   PMID:6798961
  AUTHORS   Pegg AE, Shuttleworth K, Hibasami H.
  TITLE     Specificity of mammalian spermidine synthase and spermine synthase.
  JOURNAL   Biochem J 197:315-20 (1981)
            DOI:10.1042/bj1970315
REL_PATHWAY hsa00220  Arginine biosynthesis
            hsa00250  Alanine, aspartate and glutamate metabolism
            hsa00270  Cysteine and methionine metabolism
            hsa00430  Taurine and hypotaurine metabolism
KO_PATHWAY  ko00480
///
