KEGG   PATHWAY: rtem00983
Entry
rtem00983                   Pathway                                
Name
Drug metabolism - other enzymes - Rana temporaria (common frog)
Class
Metabolism; Xenobiotics biodegradation and metabolism
Pathway map
rtem00983  Drug metabolism - other enzymes
rtem00983

Organism
Rana temporaria (common frog) [GN:rtem]
Gene
120913628  HPRT1; hypoxanthine-guanine phosphoribosyltransferase isoform X1 [KO:K00760] [EC:2.4.2.8]
120931599  IMPDH1; inosine-5'-monophosphate dehydrogenase 1 isoform X1 [KO:K00088] [EC:1.1.1.205]
120945065  IMPDH2; inosine-5'-monophosphate dehydrogenase 2 isoform X1 [KO:K00088] [EC:1.1.1.205]
120936682  GMPS; GMP synthase [glutamine-hydrolyzing] [KO:K01951] [EC:6.3.5.2]
120940748  thiopurine S-methyltransferase-like [KO:K00569] [EC:2.1.1.67]
120940750  thiopurine S-methyltransferase-like [KO:K00569] [EC:2.1.1.67]
120937824  XDH; xanthine dehydrogenase/oxidase [KO:K00106] [EC:1.17.1.4 1.17.3.2]
120945753  ITPA; inosine triphosphate pyrophosphatase [KO:K01519] [EC:3.6.1.66]
120917793  carboxylesterase 5A-like isoform X1 [KO:K03927] [EC:3.1.1.1 3.1.1.84 3.1.1.56]
120917802  cocaine esterase-like isoform X1 [KO:K03927] [EC:3.1.1.1 3.1.1.84 3.1.1.56]
120916838  uncharacterized protein LOC120916838 [KO:K03927] [EC:3.1.1.1 3.1.1.84 3.1.1.56]
120917808  fatty acyl-CoA hydrolase precursor, medium chain-like [KO:K03927] [EC:3.1.1.1 3.1.1.84 3.1.1.56]
120916837  uncharacterized protein LOC120916837 [KO:K03927] [EC:3.1.1.1 3.1.1.84 3.1.1.56]
120942718  UDP-glucuronosyltransferase 1A1-like [KO:K00699] [EC:2.4.1.17]
120915433  UDP-glucuronosyltransferase 2A1-like isoform X1 [KO:K00699] [EC:2.4.1.17]
120943901  UDP-glucuronosyltransferase 1A1-like isoform X1 [KO:K00699] [EC:2.4.1.17]
120944433  UDP-glucuronosyltransferase 1A9-like [KO:K00699] [EC:2.4.1.17]
120926640  GUSB; beta-glucuronidase [KO:K01195] [EC:3.2.1.31]
120915943  CDA; cytidine deaminase [KO:K01489] [EC:3.5.4.5]
120931586  thymidine phosphorylase [KO:K00758] [EC:2.4.2.4]
120945656  DPYD; dihydropyrimidine dehydrogenase [NADP(+)] [KO:K00207] [EC:1.3.1.2]
120941450  DPYS; dihydropyrimidinase isoform X1 [KO:K01464] [EC:3.5.2.2]
120936790  UPB1; beta-ureidopropionase [KO:K01431] [EC:3.5.1.6]
120940451  UPP1; uridine phosphorylase 1 [KO:K00757] [EC:2.4.2.3]
120944092  UPP2; uridine phosphorylase 2 isoform X1 [KO:K00757] [EC:2.4.2.3]
120919534  UCKL1; uridine-cytidine kinase-like 1 isoform X1 [KO:K00876] [EC:2.7.1.48]
120913996  UCK1; uridine-cytidine kinase 1 isoform X1 [KO:K00876] [EC:2.7.1.48]
120935953  uridine-cytidine kinase-like 1 isoform X1 [KO:K00876] [EC:2.7.1.48]
120945533  UCK2; uridine-cytidine kinase 2 [KO:K00876] [EC:2.7.1.48]
120917729  TK2; thymidine kinase 2, mitochondrial [KO:K00857] [EC:2.7.1.21]
120919071  TK1; thymidine kinase, cytosolic [KO:K00857] [EC:2.7.1.21]
120945945  CMPK1; UMP-CMP kinase [KO:K13800] [EC:2.7.4.14]
120936348  RRM2; ribonucleoside-diphosphate reductase subunit M2 [KO:K10808] [EC:1.17.4.1]
120930376  LOW QUALITY PROTEIN: nucleoside diphosphate kinase A2 [KO:K00940] [EC:2.7.4.6]
120931583  NME6; nucleoside diphosphate kinase 6 [KO:K00940] [EC:2.7.4.6]
120943321  NME4; nucleoside diphosphate kinase, mitochondrial [KO:K00940] [EC:2.7.4.6]
120943377  NME3; nucleoside diphosphate kinase 3 [KO:K00940] [EC:2.7.4.6]
120926990  NME7; nucleoside diphosphate kinase 7 [KO:K00940] [EC:2.7.4.6]
120931331  DUT; deoxyuridine 5'-triphosphate nucleotidohydrolase, mitochondrial [KO:K01520] [EC:3.6.1.23]
120927532  myeloperoxidase-like [KO:K10789] [EC:1.11.2.2]
120927666  myeloperoxidase-like isoform X1 [KO:K10789] [EC:1.11.2.2]
120927668  myeloperoxidase-like [KO:K10789] [EC:1.11.2.2]
120927671  eosinophil peroxidase-like [KO:K10789] [EC:1.11.2.2]
120917951  arylamine N-acetyltransferase, pineal gland isozyme NAT-10-like [KO:K00622] [EC:2.3.1.5]
120936974  GSTA5; glutathione S-transferase A5 [KO:K00799] [EC:2.5.1.18]
120946961  glutathione S-transferase omega-1-like [KO:K00799] [EC:2.5.1.18]
120946962  glutathione S-transferase omega-1-like [KO:K00799] [EC:2.5.1.18]
120946963  glutathione S-transferase omega-1-like [KO:K00799] [EC:2.5.1.18]
120919171  microsomal glutathione S-transferase 2-like [KO:K00799] [EC:2.5.1.18]
120919183  microsomal glutathione S-transferase 2-like isoform X1 [KO:K00799] [EC:2.5.1.18]
120941680  glutathione S-transferase theta-1-like [KO:K00799] [EC:2.5.1.18]
120932792  MGST1; microsomal glutathione S-transferase 1 isoform X1 [KO:K00799] [EC:2.5.1.18]
120926868  microsomal glutathione S-transferase 3-like [KO:K00799] [EC:2.5.1.18]
120927160  GSTM4; glutathione S-transferase Mu 4 [KO:K00799] [EC:2.5.1.18]
120936647  GSTT4; glutathione S-transferase theta-4 [KO:K00799] [EC:2.5.1.18]
120945530  MGST3; microsomal glutathione S-transferase 3 [KO:K00799] [EC:2.5.1.18]
120909156  glutathione S-transferase P 1-like isoform X1 [KO:K23790] [EC:2.5.1.18]
120909159  glutathione S-transferase P 1-like [KO:K23790] [EC:2.5.1.18]
120909162  glutathione S-transferase P 1-like [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
  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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