KEGG   PATHWAY: xla00983
Entry
xla00983                    Pathway                                
Name
Drug metabolism - other enzymes - Xenopus laevis (African clawed frog)
Class
Metabolism; Xenobiotics biodegradation and metabolism
Pathway map
xla00983  Drug metabolism - other enzymes
xla00983

Organism
Xenopus laevis (African clawed frog) [GN:xla]
Gene
779138  hprt1.L; hypoxanthine phosphoribosyltransferase 1 L homeolog [KO:K00760] [EC:2.4.2.8]
108700178  hypoxanthine-guanine phosphoribosyltransferase isoform X1 [KO:K00760] [EC:2.4.2.8]
398453  impdh2.S; IMP (inosine 5'-monophosphate) dehydrogenase 2 [KO:K00088] [EC:1.1.1.205]
399236  impdh2.L; inosine 5'-phosphate dehydrogenase 2 [KO:K00088] [EC:1.1.1.205]
380485  impdh1.L; inosine monophosphate dehydrogenase 1 [KO:K00088] [EC:1.1.1.205]
108713018  inosine-5'-monophosphate dehydrogenase 1 isoform X1 [KO:K00088] [EC:1.1.1.205]
100380966  gmps.L; GMP synthase [glutamine-hydrolyzing] isoform X1 [KO:K01951] [EC:6.3.5.2]
108718118  gmps.S; GMP synthase [glutamine-hydrolyzing] [KO:K01951] [EC:6.3.5.2]
447769  tpmt.L; thiopurine S-methyltransferase L homeolog [KO:K00569] [EC:2.1.1.67]
108704455  probable thiopurine S-methyltransferase [KO:K00569] [EC:2.1.1.67]
108717383  xdh.S; xanthine dehydrogenase/oxidase-like [KO:K00106] [EC:1.17.1.4 1.17.3.2]
108716095  xdh.L; xanthine dehydrogenase/oxidase isoform X1 [KO:K00106] [EC:1.17.1.4 1.17.3.2]
735008  itpa.S; inosine triphosphate pyrophosphatase [KO:K01519] [EC:3.6.1.66]
108714409  inosine triphosphate pyrophosphatase-like isoform X2 [KO:K01519] [EC:3.6.1.66]
108713509  cocaine esterase [KO:K03927] [EC:3.1.1.1 3.1.1.84 3.1.1.56]
100381172  ces3.4.L; carboxylesterase 5A [KO:K03927] [EC:3.1.1.1 3.1.1.84 3.1.1.56]
108714107  carboxylesterase 5A [KO:K03927] [EC:3.1.1.1 3.1.1.84 3.1.1.56]
108714105  cocaine esterase-like isoform X1 [KO:K03927] [EC:3.1.1.1 3.1.1.84 3.1.1.56]
100037183  ugt1a6.S; UDP-glucuronosyltransferase 1-6 [KO:K00699] [EC:2.4.1.17]
108701409  ugt1a1.L; UDP-glucuronosyltransferase 1A1 isoform X1 [KO:K00699] [EC:2.4.1.17]
108711396  UDP-glucuronosyltransferase 2C1 [KO:K00699] [EC:2.4.1.17]
108709643  gusb.S; beta-glucuronidase isoform X1 [KO:K01195] [EC:3.2.1.31]
108708332  gusb.L; beta-glucuronidase isoform X1 [KO:K01195] [EC:3.2.1.31]
108697878  cda.S; cytidine deaminase [KO:K01489] [EC:3.5.4.5]
108696867  cda.L; cytidine deaminase [KO:K01489] [EC:3.5.4.5]
108710281  tymp.L; thymidine phosphorylase [KO:K00758] [EC:2.4.2.4]
447312  dpyd.L; dihydropyrimidine dehydrogenase [NADP(+)] [KO:K00207] [EC:1.3.1.2]
495311  dpys.L; dihydropyrimidinase L homeolog [KO:K01464] [EC:3.5.2.2]
108695418  dpys.S; dihydropyrimidinase [KO:K01464] [EC:3.5.2.2]
447326  upb1.S; ureidopropionase, beta S homeolog [KO:K01431] [EC:3.5.1.6]
496317  upp2.S; uridine phosphorylase 2 S homeolog [KO:K00757] [EC:2.4.2.3]
108701336  upp2.L; uridine phosphorylase 2 isoform X1 [KO:K00757] [EC:2.4.2.3]
108718990  upp1.L; uridine phosphorylase 1 [KO:K00757] [EC:2.4.2.3]
496224  uckl1.L; uridine-cytidine kinase 1-like 1 L homeolog [KO:K00876] [EC:2.7.1.48]
494739  uck2.S; uridine-cytidine kinase 2 S homeolog [KO:K00876] [EC:2.7.1.48]
398966  uck1.S; uridine-cytidine kinase 1-A [KO:K00876] [EC:2.7.1.48]
444114  MGC80465; uridine-cytidine kinase 1-B [KO:K00876] [EC:2.7.1.48]
108718334  uckl1.S; uridine-cytidine kinase-like 1 isoform X1 [KO:K00876] [EC:2.7.1.48]
108702047  uridine-cytidine kinase-like 1 isoform X3 [KO:K00876] [EC:2.7.1.48]
108714503  uridine-cytidine kinase 2 [KO:K00876] [EC:2.7.1.48]
108701015  tk1.L; thymidine kinase, cytosolic [KO:K00857] [EC:2.7.1.21]
108713505  thymidine kinase 2, mitochondrial-like [KO:K00857] [EC:2.7.1.21]
398276  tk2.S; thymidine kinase 2, mitochondrial S homeolog [KO:K00857] [EC:2.7.1.21]
494728  umps.L; uridine 5'-monophosphate synthase [KO:K13421] [EC:2.4.2.10 4.1.1.23]
398670  cmpk1.S; UMP-CMP kinase [KO:K13800] [EC:2.7.4.14]
108714299  cmpk1.L; UMP-CMP kinase [KO:K13800] [EC:2.7.4.14]
399431  rrm1.L; ribonucleotide reductase M1 L homeolog [KO:K10807] [EC:1.17.4.1]
108710085  rrm1.S; ribonucleoside-diphosphate reductase large subunit [KO:K10807] [EC:1.17.4.1]
443815  rrm2.1.L; ribonucleotide reductase M2, gene 1 L homeolog [KO:K10808] [EC:1.17.4.1]
380465  rrm2.2.L; ribonucleotide reductase M2 polypeptide [KO:K10808] [EC:1.17.4.1]
379056  rrm2b.S; ribonucleotide reductase M2 B (TP53 inducible) S homeolog [KO:K10808] [EC:1.17.4.1]
108695407  ribonucleoside-diphosphate reductase subunit M2 B [KO:K10808] [EC:1.17.4.1]
447181  nme3.L; nucleoside diphosphate kinase 3 precursor [KO:K00940] [EC:2.7.4.6]
495951  nme4.S; nucleoside diphosphate kinase 4 [KO:K00940] [EC:2.7.4.6]
399333  nme2.S; nucleoside diphosphate kinase A2 [KO:K00940] [EC:2.7.4.6]
414658  nme4.L; nucleoside diphosphate kinase 4 [KO:K00940] [EC:2.7.4.6]
100037175  nme3.S; nucleoside diphosphate kinase 3 precursor [KO:K00940] [EC:2.7.4.6]
734821  nme6.S; LOW QUALITY PROTEIN: nucleoside diphosphate kinase 6 [KO:K00940] [EC:2.7.4.6]
394350  nme2.L; nucleoside diphosphate kinase A1 [KO:K00940] [EC:2.7.4.6]
108708207  nme7.L; nucleoside diphosphate kinase 7 isoform X1 [KO:K00940] [EC:2.7.4.6]
108711261  nme6.L; nucleoside diphosphate kinase 6 [KO:K00940] [EC:2.7.4.6]
108709411  nme7.S; nucleoside diphosphate kinase 7 isoform X1 [KO:K00940] [EC:2.7.4.6]
100037200  dut.L; deoxyuridine triphosphatase L homeolog [KO:K01520] [EC:3.6.1.23]
108712910  dut.S; deoxyuridine 5'-triphosphate nucleotidohydrolase, mitochondrial [KO:K01520] [EC:3.6.1.23]
394386  mpo.L; myeloperoxidase precursor [KO:K10789] [EC:1.11.2.2]
398084  epx.L; eosinophil peroxidase precursor [KO:K10789] [EC:1.11.2.2]
373710  mpo.S; myeloperoxidase isoform X2 [KO:K10789] [EC:1.11.2.2]
444764  mgst3.S; microsomal glutathione S-transferase 3 S homeolog [KO:K00799] [EC:2.5.1.18]
414684  mgst1.L; microsomal glutathione S-transferase 1 L homeolog [KO:K00799] [EC:2.5.1.18]
380534  gstm1.S; glutathione S-transferase mu 2 [KO:K00799] [EC:2.5.1.18]
432297  gstt1.L; glutathione S-transferase theta 1 L homeolog [KO:K00799] [EC:2.5.1.18]
100036918  uncharacterized protein LOC100036918 [KO:K00799] [EC:2.5.1.18]
495981  mgst3.L; uncharacterized protein LOC495981 [KO:K00799] [EC:2.5.1.18]
734548  gsta4.S; glutathione S-transferase alpha 4 S homeolog [KO:K00799] [EC:2.5.1.18]
431979  MGC82327; uncharacterized protein LOC431979 [KO:K00799] [EC:2.5.1.18]
100037104  gsto2.L; glutathione S-transferase omega 2 L homeolog [KO:K00799] [EC:2.5.1.18]
100037213  XB5796436.L; uncharacterized protein LOC100037213 [KO:K00799] [EC:2.5.1.18]
100036921  gsta1.L; glutathione S-transferase alpha 1 L homeolog [KO:K00799] [EC:2.5.1.18]
108716906  glutathione S-transferase 3 [KO:K00799] [EC:2.5.1.18]
446920  gsta1.S; glutathione S-transferase 3 isoform X2 [KO:K00799] [EC:2.5.1.18]
779251  gstt1-like.2.L; uncharacterized protein LOC779251 [KO:K00799] [EC:2.5.1.18]
495374  gsto1.S; glutathione S-transferase omega 1 S homeolog [KO:K00799] [EC:2.5.1.18]
108716035  glutathione S-transferase theta-1 [KO:K00799] [EC:2.5.1.18]
108699647  mgst2.L; microsomal glutathione S-transferase 2 isoform X2 [KO:K00799] [EC:2.5.1.18]
108706060  mgst2.S; microsomal glutathione S-transferase 2 [KO:K00799] [EC:2.5.1.18]
108696140  glutathione S-transferase omega-1 [KO:K00799] [EC:2.5.1.18]
108699671  microsomal glutathione S-transferase 2 [KO:K00799] [EC:2.5.1.18]
108709596  XB5796436.S; microsomal glutathione S-transferase 3 [KO:K00799] [EC:2.5.1.18]
398321  gstp1.L; glutathione S-transferase P 1 [KO:K23790] [EC:2.5.1.18]
121397248  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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