KEGG   PATHWAY: ptg00983
Entry
ptg00983                    Pathway                                

Name
Drug metabolism - other enzymes - Panthera tigris altaica (Amur tiger)
Class
Metabolism; Xenobiotics biodegradation and metabolism
Pathway map
ptg00983  Drug metabolism - other enzymes
ptg00983

Organism
Panthera tigris altaica (Amur tiger) [GN:ptg]
Gene
102954897  HPRT1; hypoxanthine phosphoribosyltransferase 1 [KO:K00760] [EC:2.4.2.8]
102967384  IMPDH1; inosine monophosphate dehydrogenase 1 [KO:K00088] [EC:1.1.1.205]
102970926  IMPDH2; inosine monophosphate dehydrogenase 2 [KO:K00088] [EC:1.1.1.205]
102954094  GMPS; guanine monophosphate synthase [KO:K01951] [EC:6.3.5.2]
102956395  TPMT; thiopurine S-methyltransferase [KO:K00569] [EC:2.1.1.67]
102969928  xanthine dehydrogenase/oxidase [KO:K00106] [EC:1.17.1.4 1.17.3.2]
102959510  ITPA; inosine triphosphatase [KO:K01519] [EC:3.6.1.-]
102957516  CES1; carboxylesterase 1 [KO:K01044] [EC:3.1.1.1]
102953134  CES2; carboxylesterase 2 [KO:K03927] [EC:3.1.1.1 3.1.1.84 3.1.1.56]
102959578  UGT1A1; UDP-glucuronosyltransferase 1-1 [KO:K00699] [EC:2.4.1.17]
102967993  UDP-glucuronosyltransferase 2A1-like [KO:K00699] [EC:2.4.1.17]
102968284  UGT2A1; UDP-glucuronosyltransferase 2A1 [KO:K00699] [EC:2.4.1.17]
102964512  GUSB; glucuronidase beta [KO:K01195] [EC:3.2.1.31]
102955418  CDA; cytidine deaminase [KO:K01489] [EC:3.5.4.5]
102967087  DPYS; dihydropyrimidinase [KO:K01464] [EC:3.5.2.2]
102958013  UPB1; beta-ureidopropionase 1 [KO:K01431] [EC:3.5.1.6]
102952667  UPP1; uridine phosphorylase 1 [KO:K00757] [EC:2.4.2.3]
102962326  UCK1; uridine-cytidine kinase 1 [KO:K00876] [EC:2.7.1.48]
102971572  UCK2; uridine-cytidine kinase 2 [KO:K00876] [EC:2.7.1.48]
102953321  UCKL1; uridine-cytidine kinase 1 like 1 [KO:K00876] [EC:2.7.1.48]
102950807  TK2; thymidine kinase 2, mitochondrial [KO:K00857] [EC:2.7.1.21]
107180503  TK1; thymidine kinase 1 [KO:K00857] [EC:2.7.1.21]
102970593  UMPS; uridine monophosphate synthetase [KO:K13421] [EC:2.4.2.10 4.1.1.23]
102951048  CMPK1; cytidine/uridine monophosphate kinase 1 [KO:K13800] [EC:2.7.4.14]
102953329  RRM1; ribonucleotide reductase catalytic subunit M1 [KO:K10807] [EC:1.17.4.1]
102950840  RRM2B; ribonucleotide reductase regulatory TP53 inducible subunit M2B [KO:K10808] [EC:1.17.4.1]
102950263  RRM2; ribonucleotide reductase regulatory subunit M2 [KO:K10808] [EC:1.17.4.1]
102963448  NME7; NME/NM23 family member 7 [KO:K00940] [EC:2.7.4.6]
102970480  NME4; NME/NM23 nucleoside diphosphate kinase 4 [KO:K00940] [EC:2.7.4.6]
102962166  NME6; NME/NM23 nucleoside diphosphate kinase 6 [KO:K00940] [EC:2.7.4.6]
102967905  NME2; NME/NM23 nucleoside diphosphate kinase 2 [KO:K00940] [EC:2.7.4.6]
102953403  DUT; deoxyuridine triphosphatase [KO:K01520] [EC:3.6.1.23]
107181092  deoxyuridine 5'-triphosphate nucleotidohydrolase, mitochondrial-like [KO:K01520] [EC:3.6.1.23]
102973033  MPO; myeloperoxidase [KO:K10789] [EC:1.11.2.2]
102955781  NAT1; arylamine N-acetyltransferase 1 [KO:K00622] [EC:2.3.1.5]
102969051  cytochrome P450 2E1 [KO:K07415] [EC:1.14.14.-]
102971089  MGST3; microsomal glutathione S-transferase 3 [KO:K00799] [EC:2.5.1.18]
102966922  GSTO1; glutathione S-transferase omega 1 [KO:K00799] [EC:2.5.1.18]
102967394  GSTO2; glutathione S-transferase omega 2 [KO:K00799] [EC:2.5.1.18]
102955989  MGST1; microsomal glutathione S-transferase 1 [KO:K00799] [EC:2.5.1.18]
102962954  MGST2; microsomal glutathione S-transferase 2 [KO:K00799] [EC:2.5.1.18]
102970472  glutathione S-transferase theta-2B-like [KO:K00799] [EC:2.5.1.18]
102960578  glutathione S-transferase theta-1-like [KO:K00799] [EC:2.5.1.18]
102959987  glutathione S-transferase theta-1-like [KO:K00799] [EC:2.5.1.18]
102960295  glutathione S-transferase theta-1 [KO:K00799] [EC:2.5.1.18]
102958890  glutathione S-transferase A4 [KO:K00799] [EC:2.5.1.18]
102958324  GSTA2; glutathione S-transferase A2 [KO:K00799] [EC:2.5.1.18]
102949073  glutathione S-transferase-like [KO:K00799] [EC:2.5.1.18]
102958599  glutathione S-transferase A4-like [KO:K00799] [EC:2.5.1.18]
102949368  glutathione S-transferase alpha M14-like [KO:K00799] [EC:2.5.1.18]
102949663  GSTM3; glutathione S-transferase Mu 3 [KO:K00799] [EC:2.5.1.18]
102949366  GSTM4; glutathione S-transferase Mu 4 [KO:K00799] [EC:2.5.1.18]
102960863  glutathione S-transferase theta-4-like [KO:K00799] [EC:2.5.1.18]
102964863  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 (JP17/USP/INN)
D00346  Isoniazid (JP17/USP/INN)
D00584  Fluorouracil (JP17/USP/INN)
D01223  Capecitabine (JAN/USP/INN)
D01244  Tegafur (JP17/USAN/INN)
D01309  Doxifluridine (JP17/INN)
D01784  Carmofur (JP17/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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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   
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