KEGG   PATHWAY: ssc00983
Entry
ssc00983                    Pathway                                
Name
Drug metabolism - other enzymes - Sus scrofa (pig)
Class
Metabolism; Xenobiotics biodegradation and metabolism
Pathway map
ssc00983  Drug metabolism - other enzymes
ssc00983

Organism
Sus scrofa (pig) [GN:ssc]
Gene
397351  HPRT1; hypoxanthine-guanine phosphoribosyltransferase [KO:K00760] [EC:2.4.2.8]
100525485  IMPDH2; inosine-5'-monophosphate dehydrogenase 2 isoform X2 [KO:K00088] [EC:1.1.1.205]
100520873  IMPDH1; inosine-5'-monophosphate dehydrogenase 1 isoform X1 [KO:K00088] [EC:1.1.1.205]
100512255  GMPS; GMP synthase [glutamine-hydrolyzing] isoform X2 [KO:K01951] [EC:6.3.5.2]
100157630  TPMT; thiopurine S-methyltransferase [KO:K00569] [EC:2.1.1.67]
100515259  XDH; xanthine dehydrogenase/oxidase [KO:K00106] [EC:1.17.1.4 1.17.3.2]
100157088  ITPA; inosine triphosphate pyrophosphatase isoform X3 [KO:K01519] [EC:3.6.1.66]
397478  CES1; liver carboxylesterase precursor [KO:K01044] [EC:3.1.1.1]
100736962  liver carboxylesterase precursor [KO:K01044] [EC:3.1.1.1]
100152603  UGT1A6; UDP glucuronosyltransferase 1 family, polypeptide A6 precursor [KO:K00699] [EC:2.4.1.17]
100515394  UDP-glucuronosyltransferase 2C1 [KO:K00699] [EC:2.4.1.17]
100515741  LOW QUALITY PROTEIN: UDP-glucuronosyltransferase 2B31 [KO:K00699] [EC:2.4.1.17]
100516628  UDP-glucuronosyltransferase 2B18-like isoform X1 [KO:K00699] [EC:2.4.1.17]
100624700  UDP-glucuronosyltransferase 2C1-like isoform X1 [KO:K00699] [EC:2.4.1.17]
100624788  UDP-glucuronosyltransferase 2A1 isoform X2 [KO:K00699] [EC:2.4.1.17]
100623255  LOW QUALITY PROTEIN: UDP-glucuronosyltransferase 2B31 [KO:K00699] [EC:2.4.1.17]
100514063  UGT2B31; UDP-glucuronosyltransferase 2B31 precursor [KO:K00699] [EC:2.4.1.17]
100624891  UDP-glucuronosyltransferase 2C1 [KO:K00699] [EC:2.4.1.17]
100623504  LOW QUALITY PROTEIN: UDP-glucuronosyltransferase 2B31-like [KO:K00699] [EC:2.4.1.17]
100515222  UDP-glucuronosyltransferase 2C1 isoform X1 [KO:K00699] [EC:2.4.1.17]
110262116  UDP-glucuronosyltransferase 2C1-like [KO:K00699] [EC:2.4.1.17]
100144519  GUSB; beta-glucuronidase precursor [KO:K01195] [EC:3.2.1.31]
100515954  CDA; cytidine deaminase [KO:K01489] [EC:3.5.4.5]
397109  DPYD; dihydropyrimidine dehydrogenase [NADP(+)] precursor [KO:K00207] [EC:1.3.1.2]
100156500  DPYS; dihydropyrimidinase isoform X1 [KO:K01464] [EC:3.5.2.2]
100155919  UPB1; beta-ureidopropionase isoform X1 [KO:K01431] [EC:3.5.1.6]
100522709  UPP2; uridine phosphorylase 2 [KO:K00757] [EC:2.4.2.3]
100625277  UPP1; uridine phosphorylase 1 [KO:K00757] [EC:2.4.2.3]
100525976  UCK1; uridine-cytidine kinase 1 isoform X2 [KO:K00876] [EC:2.7.1.48]
110257383  UCKL1; uridine-cytidine kinase-like 1 isoform X1 [KO:K00876] [EC:2.7.1.48]
110260302  UCK2; uridine-cytidine kinase 2 [KO:K00876] [EC:2.7.1.48]
100627619  TK2; thymidine kinase 2, mitochondrial isoform X1 [KO:K00857] [EC:2.7.1.21]
110255958  TK1; thymidine kinase, cytosolic [KO:K00857] [EC:2.7.1.21]
100516340  UMPS; uridine 5'-monophosphate synthase [KO:K13421] [EC:2.4.2.10 4.1.1.23]
100521561  CMPK1; UMP-CMP kinase [KO:K13800] [EC:2.7.4.14]
102166900  RRM1; LOW QUALITY PROTEIN: ribonucleoside-diphosphate reductase large subunit [KO:K10807] [EC:1.17.4.1]
100157205  RRM2B; ribonucleoside-diphosphate reductase subunit M2 B isoform X2 [KO:K10808] [EC:1.17.4.1]
100316853  RRM2; ribonucleoside-diphosphate reductase subunit M2 [KO:K10808] [EC:1.17.4.1]
100152763  NME7; nucleoside diphosphate kinase 7 isoform X1 [KO:K00940] [EC:2.7.4.6]
100233195  NME4; nucleoside diphosphate kinase, mitochondrial [KO:K00940] [EC:2.7.4.6]
733683  NME2; nucleoside diphosphate kinase B [KO:K00940] [EC:2.7.4.6]
100514398  NME3; nucleoside diphosphate kinase 3 isoform 1 precursor [KO:K00940] [EC:2.7.4.6]
100520587  NME6; nucleoside diphosphate kinase 6 [KO:K00940] [EC:2.7.4.6]
100142626  NME1; nucleoside diphosphate kinase A [KO:K00940] [EC:2.7.4.6]
100621123  DUT; deoxyuridine 5'-triphosphate nucleotidohydrolase, mitochondrial isoform X1 [KO:K01520] [EC:3.6.1.23]
100517120  MPO; LOW QUALITY PROTEIN: myeloperoxidase [KO:K10789] [EC:1.11.2.2]
100511905  arylamine N-acetyltransferase 1 [KO:K00622] [EC:2.3.1.5]
403216  CYP2E1; cytochrome P450 2E1 [KO:K07415] [EC:1.14.14.-]
397117  GSTO1; glutathione S-transferase omega-1 [KO:K00799] [EC:2.5.1.18]
397567  MGST1; microsomal glutathione S-transferase 1 [KO:K00799] [EC:2.5.1.18]
397682  GSTA1; glutathione S-transferase alpha M14 [KO:K00799] [EC:2.5.1.18]
100152951  GSTA4; glutathione S-transferase A4 [KO:K00799] [EC:2.5.1.18]
100153094  glutathione S-transferase theta-1 [KO:K00799] [EC:2.5.1.18]
780435  glutathione S-transferase mu 2 [KO:K00799] [EC:2.5.1.18]
733607  MGST3; microsomal glutathione S-transferase 3 [KO:K00799] [EC:2.5.1.18]
100152209  glutathione S-transferase omega-2 [KO:K00799] [EC:2.5.1.18]
100510917  glutathione S-transferase A4 [KO:K00799] [EC:2.5.1.18]
100514231  GSTM3; glutathione S-transferase Mu 3 [KO:K00799] [EC:2.5.1.18]
100622296  MGST2; microsomal glutathione S-transferase 2 [KO:K00799] [EC:2.5.1.18]
106510200  glutathione S-transferase Mu 1 [KO:K00799] [EC:2.5.1.18]
100151901  glutathione S-transferase theta-4 [KO:K00799] [EC:2.5.1.18]
110260350  LOW QUALITY PROTEIN: glutathione S-transferase Mu 1-like [KO:K00799] [EC:2.5.1.18]
110260348  glutathione S-transferase Mu 1-like isoform X1 [KO:K00799] [EC:2.5.1.18]
100526118  glutathione S-transferase A1-like [KO:K00799] [EC:2.5.1.18]
100739163  glutathione S-transferase P-like isoform X1 [KO:K23790] [EC:2.5.1.18]
100739508  glutathione S-transferase P-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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