ENTRY       hsa00983                    Pathway
NAME        Drug metabolism - other enzymes - Homo sapiens (human)
CLASS       Metabolism; Xenobiotics biodegradation and metabolism
PATHWAY_MAP hsa00983  Drug metabolism - other enzymes
DRUG        D03998  Eniluracil (USAN/INN)
            D12387  Fosgemcitabine palabenamide (USAN/INN)
            D12465  Doxecitine (USAN/INN)
            D12466  Doxribtimine (USAN/INN)
ORGANISM    Homo sapiens (human) [GN:hsa]
GENE        3251  HPRT1; hypoxanthine phosphoribosyltransferase 1 [KO:K00760] [EC:2.4.2.8]
            3614  IMPDH1; inosine monophosphate dehydrogenase 1 [KO:K00088] [EC:1.1.1.205]
            3615  IMPDH2; inosine monophosphate dehydrogenase 2 [KO:K00088] [EC:1.1.1.205]
            8833  GMPS; guanine monophosphate synthase [KO:K01951] [EC:6.3.5.2]
            7172  TPMT; thiopurine S-methyltransferase [KO:K00569] [EC:2.1.1.67]
            7498  XDH; xanthine dehydrogenase [KO:K00106] [EC:1.17.1.4 1.17.3.2]
            3704  ITPA; inosine triphosphatase [KO:K01519] [EC:3.6.1.66]
            1066  CES1; carboxylesterase 1 [KO:K01044] [EC:3.1.1.1]
            8824  CES2; carboxylesterase 2 [KO:K03927] [EC:3.1.1.1 3.1.1.84 3.1.1.56]
            10941  UGT2A1; UDP glucuronosyltransferase family 2 member A1 complex locus [KO:K00699] [EC:2.4.1.17]
            79799  UGT2A3; UDP glucuronosyltransferase family 2 member A3 [KO:K00699] [EC:2.4.1.17]
            7367  UGT2B17; UDP glucuronosyltransferase family 2 member B17 [KO:K00699] [EC:2.4.1.17]
            10720  UGT2B11; UDP glucuronosyltransferase family 2 member B11 [KO:K00699] [EC:2.4.1.17]
            54490  UGT2B28; UDP glucuronosyltransferase family 2 member B28 [KO:K00699] [EC:2.4.1.17]
            54578  UGT1A6; UDP glucuronosyltransferase family 1 member A6 [KO:K00699] [EC:2.4.1.17]
            54657  UGT1A4; UDP glucuronosyltransferase family 1 member A4 [KO:K00699] [EC:2.4.1.17]
            54658  UGT1A1; UDP glucuronosyltransferase family 1 member A1 [KO:K00699] [EC:2.4.1.17]
            54659  UGT1A3; UDP glucuronosyltransferase family 1 member A3 [KO:K00699] [EC:2.4.1.17]
            7365  UGT2B10; UDP glucuronosyltransferase family 2 member B10 [KO:K00699] [EC:2.4.1.17]
            54600  UGT1A9; UDP glucuronosyltransferase family 1 member A9 [KO:K00699] [EC:2.4.1.17]
            7364  UGT2B7; UDP glucuronosyltransferase family 2 member B7 [KO:K00699] [EC:2.4.1.17]
            54575  UGT1A10; UDP glucuronosyltransferase family 1 member A10 [KO:K00699] [EC:2.4.1.17]
            54576  UGT1A8; UDP glucuronosyltransferase family 1 member A8 [KO:K00699] [EC:2.4.1.17]
            54579  UGT1A5; UDP glucuronosyltransferase family 1 member A5 [KO:K00699] [EC:2.4.1.17]
            7366  UGT2B15; UDP glucuronosyltransferase family 2 member B15 [KO:K00699] [EC:2.4.1.17]
            54577  UGT1A7; UDP glucuronosyltransferase family 1 member A7 [KO:K00699] [EC:2.4.1.17]
            7363  UGT2B4; UDP glucuronosyltransferase family 2 member B4 [KO:K00699] [EC:2.4.1.17]
            574537  UGT2A2; UDP glucuronosyltransferase family 2 member A2 [KO:K00699] [EC:2.4.1.17]
            2990  GUSB; glucuronidase beta [KO:K01195] [EC:3.2.1.31]
            1576  CYP3A4; cytochrome P450 family 3 subfamily A member 4 [KO:K17689] [EC:1.14.13.32 1.14.14.55 1.14.14.56 1.14.14.57 1.14.14.73 1.14.14.-]
            978  CDA; cytidine deaminase [KO:K01489] [EC:3.5.4.5]
            1890  TYMP; thymidine phosphorylase [KO:K00758] [EC:2.4.2.4]
            1806  DPYD; dihydropyrimidine dehydrogenase [KO:K00207] [EC:1.3.1.2]
            1807  DPYS; dihydropyrimidinase [KO:K01464] [EC:3.5.2.2]
            51733  UPB1; beta-ureidopropionase 1 [KO:K01431] [EC:3.5.1.6]
            1548  CYP2A6; cytochrome P450 family 2 subfamily A member 6 [KO:K17683] [EC:1.14.14.-]
            1549  CYP2A7; cytochrome P450 family 2 subfamily A member 7 [KO:K17683] [EC:1.14.14.-]
            151531  UPP2; uridine phosphorylase 2 [KO:K00757] [EC:2.4.2.3]
            7378  UPP1; uridine phosphorylase 1 [KO:K00757] [EC:2.4.2.3]
            83549  UCK1; uridine-cytidine kinase 1 [KO:K00876] [EC:2.7.1.48]
            7371  UCK2; uridine-cytidine kinase 2 [KO:K00876] [EC:2.7.1.48]
            54963  UCKL1; uridine-cytidine kinase 1 like 1 [KO:K00876] [EC:2.7.1.48]
            7084  TK2; thymidine kinase 2 [KO:K00857] [EC:2.7.1.21]
            7083  TK1; thymidine kinase 1 [KO:K00857] [EC:2.7.1.21]
            7372  UMPS; uridine monophosphate synthetase [KO:K13421] [EC:2.4.2.10 4.1.1.23]
            51727  CMPK1; cytidine/uridine monophosphate kinase 1 [KO:K13800] [EC:2.7.4.14]
            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]
            10201  NME6; NME/NM23 nucleoside diphosphate kinase 6 [KO:K00940] [EC:2.7.4.6]
            29922  NME7; NME/NM23 family member 7 [KO:K00940] [EC:2.7.4.6]
            4831  NME2; NME/NM23 nucleoside diphosphate kinase 2 [KO:K00940] [EC:2.7.4.6]
            4833  NME4; NME/NM23 nucleoside diphosphate kinase 4 [KO:K00940] [EC:2.7.4.6]
            4830  NME1; NME/NM23 nucleoside diphosphate kinase 1 [KO:K00940] [EC:2.7.4.6]
            4832  NME3; NME/NM23 nucleoside diphosphate kinase 3 [KO:K00940] [EC:2.7.4.6]
            654364  NME1-NME2; NME1-NME2 readthrough [KO:K00940] [EC:2.7.4.6]
            1854  DUT; deoxyuridine triphosphatase [KO:K01520] [EC:3.6.1.23]
            4353  MPO; myeloperoxidase [KO:K10789] [EC:1.11.2.2]
            10  NAT2; N-acetyltransferase 2 [KO:K00622] [EC:2.3.1.5]
            9  NAT1; N-acetyltransferase 1 [KO:K00622] [EC:2.3.1.5]
            1571  CYP2E1; cytochrome P450 family 2 subfamily E member 1 [KO:K07415] [EC:1.14.14.-]
            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]
COMPOUND    C00003  NAD+
            C00006  NADP+
            C02320  R-S-Glutathione
            C02380  6-Mercaptopurine
            C04242  5-Fluorodeoxyuridine monophosphate
            C04646  6-Thioinosine-5'-monophosphate
            C05361  Hydrazine
            C06108  Fluoroacetate
            C06837  Azathioprine
            C07054  Isoniazid
            C07446  Isonicotinic acid
            C07447  Acetylhydrazine
            C07585  N-Acetylisoniazid
            C07648  Thioguanine
            C07649  5-FU
            C11173  SN-38
            C11376  SN38 glucuronide
            C11736  5-Fluorodeoxyuridine
            C12650  Capecitabine
            C12673  Tegafur
            C12739  5'-Deoxy-5-fluorouridine
            C13252  Carmofur
            C16542  APC
            C16543  NPC
            C16613  6-Thiourate
            C16614  6-Methylmercaptopurine
            C16615  6-Methylthiopurine 5'-monophosphate ribonucleotide
            C16616  6-Mercaptopurine ribonucleoside 5'-diphosphate
            C16617  6-Mercaptopurine ribonucleoside triphosphate
            C16618  6-Thioxanthine 5'-monophosphate
            C16619  6-Thioguanosine monophosphate
            C16620  6-Methylthioguanosine monophosphate
            C16621  1-Methyl-4-nitroimidazole
            C16622  N,N'-Diacetylhydrazine
            C16623  Isonicotinylglycine
            C16624  Isoniazid pyruvate
            C16625  Isoniazid alpha-ketoglutaric acid
            C16630  5,6-Dihydro-5-fluorouracil
            C16631  alpha-Fluoro-beta-ureidopropionic acid
            C16632  alpha-Fluoro-beta-alanine
            C16633  5-Fluorouridine
            C16634  5-Fluorouridine monophosphate
            C16635  5'-Deoxy-5-fluorocytidine
            C16641  Irinotecan
            C21748  5-Fluorouridine diphosphate
            C21749  5-Fluorouridine triphosphate
            C21750  5-Fluorodeoxyuridine diphosphate
            C21751  5-Fluorodeoxyuridine triphosphate
            C21754  Isonicotinoyl radical
            C21758  Hepatotoxins
            C21759  Isonicotinoyl-NAD adduct
            C21760  Isonicotinoyl-NADP adduct
            D00238  Azathioprine (JP18/USP/INN)
            D00346  Isoniazid (JP18/USP/INN)
            D00584  Fluorouracil (JP18/USP/INN)
            D01223  Capecitabine (JAN/USP/INN)
            D01244  Tegafur (JP18/USAN/INN)
            D01309  Doxifluridine (JP18/INN)
            D01784  Carmofur (JP18/INN)
            D04197  Floxuridine (USP/INN)
            D04931  Mercaptopurine (INN)
            D08086  Irinotecan (INN)
            D08603  Tioguanine (INN)
REFERENCE   
  AUTHORS   Kato R, Kamatari T (eds).
  TITLE     [Drug Metabolism] (In Japanese)
  JOURNAL   Tokyo Kagaku Dojin (2000)
REFERENCE   PMID:15788214
  AUTHORS   Al Hadithy AF, de Boer NK, Derijks LJ, Escher JC, Mulder CJ, Brouwers JR.
  TITLE     Thiopurines in inflammatory bowel disease: pharmacogenetics, therapeutic drug monitoring and clinical recommendations.
  JOURNAL   Dig Liver Dis 37:282-97 (2005)
            DOI:10.1016/j.dld.2004.09.029
REFERENCE   PMID:16048561
  AUTHORS   Gearry RB, Barclay ML.
  TITLE     Azathioprine and 6-mercaptopurine pharmacogenetics and metabolite monitoring in inflammatory bowel disease.
  JOURNAL   J Gastroenterol Hepatol 20:1149-57 (2005)
            DOI:10.1111/j.1440-1746.2005.03832.x
REFERENCE   PMID:16880012
  AUTHORS   Gilissen LP, Derijks LJ, Verhoeven HM, Bierau J, Hooymans PM, Hommes DW, Engels LG.
  TITLE     Pancytopenia due to high 6-methylmercaptopurine levels in a 6-mercaptopurine treated patient with Crohn's disease.
  JOURNAL   Dig Liver Dis 39:182-6 (2007)
            DOI:10.1016/j.dld.2006.05.026
REFERENCE   PMID:15514566
  AUTHORS   Fischel JL, Formento P, Ciccolini J, Etienne-Grimaldi MC, Milano G.
  TITLE     Lack of contribution of dihydrofluorouracil and alpha-fluoro-beta-alanine to the cytotoxicity of 5'-deoxy-5-fluorouridine on human keratinocytes.
  JOURNAL   Anticancer Drugs 15:969-74 (2004)
            DOI:10.1097/00001813-200411000-00006
REFERENCE   PMID:10976516
  AUTHORS   Shimma N, Umeda I, Arasaki M, Murasaki C, Masubuchi K, Kohchi Y, Miwa M, Ura M, Sawada N, Tahara H, Kuruma I, Horii I, Ishitsuka H.
  TITLE     The design and synthesis of a new tumor-selective fluoropyrimidine carbamate, capecitabine.
  JOURNAL   Bioorg Med Chem 8:1697-706 (2000)
            DOI:10.1016/S0968-0896(00)00087-0
REFERENCE   PMID:15173095
  AUTHORS   Chung YL, Troy H, Judson IR, Leek R, Leach MO, Stubbs M, Harris AL, Griffiths JR
  TITLE     Noninvasive measurements of capecitabine metabolism in bladder tumors overexpressing thymidine phosphorylase by fluorine-19 magnetic resonance spectroscopy.
  JOURNAL   Clin Cancer Res 10:3863-70 (2004)
            DOI:10.1158/1078-0432.CCR-03-0237
REFERENCE   PMID:11489791
  AUTHORS   Mathijssen RH, van Alphen RJ, Verweij J, Loos WJ, Nooter K, Stoter G, Sparreboom A
  TITLE     Clinical pharmacokinetics and metabolism of irinotecan (CPT-11).
  JOURNAL   Clin Cancer Res 7:2182-94 (2001)
REFERENCE   PMID:11379777
  AUTHORS   Kita T, Tanigawara Y, Chikazawa S, Hatanaka H, Sakaeda T, Komada F, Iwakawa S, Okumura K.
  TITLE     N-Acetyltransferase2 genotype correlated with isoniazid acetylation in Japanese tuberculous patients.
  JOURNAL   Biol Pharm Bull 24:544-9 (2001)
            DOI:10.1248/bpb.24.544
REFERENCE   PMID:24281184
  AUTHORS   Miura K, Kinouchi M, Ishida K, Fujibuchi W, Naitoh T, Ogawa H, Ando T, Yazaki N, Watanabe K, Haneda S, Shibata C, Sasaki I
  TITLE     5-fu metabolism in cancer and orally-administrable 5-fu drugs.
  JOURNAL   Cancers (Basel) 2:1717-30 (2010)
            DOI:10.3390/cancers2031717
REFERENCE   PMID:27709007
  AUTHORS   Wang P, Pradhan K, Zhong XB, Ma X
  TITLE     Isoniazid metabolism and hepatotoxicity.
  JOURNAL   Acta Pharm Sin B 6:384-392 (2016)
            DOI:10.1016/j.apsb.2016.07.014
REFERENCE   PMID:27232112
  AUTHORS   Klein DJ, Boukouvala S, McDonagh EM, Shuldiner SR, Laurieri N, Thorn CF, Altman RB, Klein TE
  TITLE     PharmGKB summary: isoniazid pathway, pharmacokinetics.
  JOURNAL   Pharmacogenet Genomics 26:436-44 (2016)
            DOI:10.1097/FPC.0000000000000232
REFERENCE   PMID:20195289
  AUTHORS   Yamada S, Richardson K, Tang M, Halaschek-Wiener J, Cook VJ, Fitzgerald JM, Elwood K, Marra F, Brooks-Wilson A
  TITLE     Genetic variation in carboxylesterase genes and susceptibility to isoniazid-induced hepatotoxicity.
  JOURNAL   Pharmacogenomics J 10:524-36 (2010)
            DOI:10.1038/tpj.2010.5
REFERENCE   PMID:20434429
  AUTHORS   Vlasits J, Jakopitsch C, Bernroitner M, Zamocky M, Furtmuller PG, Obinger C
  TITLE     Mechanisms of catalase activity of heme peroxidases.
  JOURNAL   Arch Biochem Biophys 500:74-81 (2010)
            DOI:10.1016/j.abb.2010.04.018
REFERENCE   PMID:26867495
  AUTHORS   Khan SR, Morgan AG, Michail K, Srivastava N, Whittal RM, Aljuhani N, Siraki AG
  TITLE     Metabolism of isoniazid by neutrophil myeloperoxidase leads to isoniazid-NAD(+) adduct formation: A comparison of the reactivity of isoniazid with its known human metabolites.
  JOURNAL   Biochem Pharmacol 106:46-55 (2016)
            DOI:10.1016/j.bcp.2016.02.003
REFERENCE   PMID:22846601
  AUTHORS   Forbes LV, Furtmuller PG, Khalilova I, Turner R, Obinger C, Kettle AJ
  TITLE     Isoniazid as a substrate and inhibitor of myeloperoxidase: identification of amine adducts and the influence of superoxide dismutase on their formation.
  JOURNAL   Biochem Pharmacol 84:949-60 (2012)
            DOI:10.1016/j.bcp.2012.07.020
REFERENCE   PMID:12069966
  AUTHORS   Nguyen M, Quemard A, Broussy S, Bernadou J, Meunier B
  TITLE     Mn(III) pyrophosphate as an efficient tool for studying the mode of action of isoniazid on the InhA protein of Mycobacterium tuberculosis.
  JOURNAL   Antimicrob Agents Chemother 46:2137-44 (2002)
            DOI:10.1128/AAC.46.7.2137-2144.2002
REFERENCE   PMID:9417034
  AUTHORS   Rozwarski DA, Grant GA, Barton DH, Jacobs WR Jr, Sacchettini JC
  TITLE     Modification of the NADH of the isoniazid target (InhA) from Mycobacterium tuberculosis.
  JOURNAL   Science 279:98-102 (1998)
            DOI:10.1126/science.279.5347.98
REFERENCE   PMID:17636923
  AUTHORS   Argyrou A, Vetting MW, Blanchard JS
  TITLE     New insight into the mechanism of action of and resistance to isoniazid: interaction of Mycobacterium tuberculosis enoyl-ACP reductase with INH-NADP.
  JOURNAL   J Am Chem Soc 129:9582-3 (2007)
            DOI:10.1021/ja073160k
KO_PATHWAY  ko00983
///
