KEGG   PATHWAY: nle00983
Entry
nle00983                    Pathway                                
Name
Drug metabolism - other enzymes - Nomascus leucogenys (northern white-cheeked gibbon)
Class
Metabolism; Xenobiotics biodegradation and metabolism
Pathway map
nle00983  Drug metabolism - other enzymes
nle00983

Organism
Nomascus leucogenys (northern white-cheeked gibbon) [GN:nle]
Gene
100581397  HPRT1; hypoxanthine-guanine phosphoribosyltransferase isoform X1 [KO:K00760] [EC:2.4.2.8]
100598855  IMPDH2; inosine-5'-monophosphate dehydrogenase 2 isoform X1 [KO:K00088] [EC:1.1.1.205]
100581732  inosine-5'-monophosphate dehydrogenase 1 isoform X1 [KO:K00088] [EC:1.1.1.205]
100583696  IMPDH1; inosine-5'-monophosphate dehydrogenase 1 isoform X1 [KO:K00088] [EC:1.1.1.205]
100596511  LOW QUALITY PROTEIN: inosine-5'-monophosphate dehydrogenase 1-like [KO:K00088] [EC:1.1.1.205]
100591577  GMPS; GMP synthase [glutamine-hydrolyzing] [KO:K01951] [EC:6.3.5.2]
100592079  TPMT; thiopurine S-methyltransferase [KO:K00569] [EC:2.1.1.67]
100594931  XDH; xanthine dehydrogenase/oxidase [KO:K00106] [EC:1.17.1.4 1.17.3.2]
100594558  ITPA; inosine triphosphate pyrophosphatase isoform X1 [KO:K01519] [EC:3.6.1.66]
100599005  liver carboxylesterase 1 isoform X1 [KO:K01044] [EC:3.1.1.1]
100590392  CES1; liver carboxylesterase 1 isoform X1 [KO:K01044] [EC:3.1.1.1]
100605306  cocaine esterase [KO:K03927] [EC:3.1.1.1 3.1.1.84 3.1.1.56]
100599562  LOW QUALITY PROTEIN: cocaine esterase [KO:K03927] [EC:3.1.1.1 3.1.1.84 3.1.1.56]
100595736  UDP-glucuronosyltransferase 2B10 isoform X2 [KO:K00699] [EC:2.4.1.17]
100596642  UDP-glucuronosyltransferase 2B7 isoform X1 [KO:K00699] [EC:2.4.1.17]
100597206  UDP-glucuronosyltransferase 2B11 isoform X1 [KO:K00699] [EC:2.4.1.17]
100598804  UDP-glucuronosyltransferase 2B4 isoform X1 [KO:K00699] [EC:2.4.1.17]
100599929  UDP-glucuronosyltransferase 2A1 isoform X1 [KO:K00699] [EC:2.4.1.17]
100592283  UDP-glucuronosyltransferase 1-1 isoform X4 [KO:K00699] [EC:2.4.1.17]
100599361  UDP-glucuronosyltransferase 2B19 isoform X1 [KO:K00699] [EC:2.4.1.17]
100596311  UDP-glucuronosyltransferase 2A3 [KO:K00699] [EC:2.4.1.17]
105738256  UDP-glucuronosyltransferase 2B4-like [KO:K00699] [EC:2.4.1.17]
100591991  UDP-glucuronosyltransferase 2B15 isoform X1 [KO:K00699] [EC:2.4.1.17]
100595401  LOW QUALITY PROTEIN: UDP-glucuronosyltransferase 2B17 [KO:K00699] [EC:2.4.1.17]
100600348  LOW QUALITY PROTEIN: UDP-glucuronosyltransferase 1-7 [KO:K00699] [EC:2.4.1.17]
100582236  LOW QUALITY PROTEIN: beta-glucuronidase-like [KO:K01195] [EC:3.2.1.31]
100604207  beta-glucuronidase isoform X1 [KO:K01195] [EC:3.2.1.31]
100600820  beta-glucuronidase isoform X1 [KO:K01195] [EC:3.2.1.31]
100593175  cytochrome P450 3A4 isoform X3 [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.-]
100598827  CDA; cytidine deaminase [KO:K01489] [EC:3.5.4.5]
115835926  TYMP; thymidine phosphorylase [KO:K00758] [EC:2.4.2.4]
100604410  DPYD; dihydropyrimidine dehydrogenase [NADP(+)] [KO:K00207] [EC:1.3.1.2]
100606946  DPYS; dihydropyrimidinase [KO:K01464] [EC:3.5.2.2]
100597745  UPB1; beta-ureidopropionase [KO:K01431] [EC:3.5.1.6]
100607708  UPP1; uridine phosphorylase 1 isoform X1 [KO:K00757] [EC:2.4.2.3]
100595055  UPP2; uridine phosphorylase 2 isoform X2 [KO:K00757] [EC:2.4.2.3]
100583889  UCK1; uridine-cytidine kinase 1 isoform X2 [KO:K00876] [EC:2.7.1.48]
100600542  UCK2; uridine-cytidine kinase 2 [KO:K00876] [EC:2.7.1.48]
100598214  TK2; thymidine kinase 2, mitochondrial isoform X1 [KO:K00857] [EC:2.7.1.21]
100607307  TK1; thymidine kinase, cytosolic isoform X1 [KO:K00857] [EC:2.7.1.21]
100583986  UMPS; uridine 5'-monophosphate synthase [KO:K13421] [EC:2.4.2.10 4.1.1.23]
100583014  CMPK1; UMP-CMP kinase [KO:K13800] [EC:2.7.4.14]
100599741  RRM1; ribonucleoside-diphosphate reductase large subunit [KO:K10807] [EC:1.17.4.1]
100579408  RRM2; ribonucleoside-diphosphate reductase subunit M2 [KO:K10808] [EC:1.17.4.1]
100599865  RRM2B; ribonucleoside-diphosphate reductase subunit M2 B [KO:K10808] [EC:1.17.4.1]
100582337  nucleoside diphosphate kinase B isoform X2 [KO:K00940] [EC:2.7.4.6]
100589554  NME6; nucleoside diphosphate kinase 6 isoform X1 [KO:K00940] [EC:2.7.4.6]
100586165  NME4; nucleoside diphosphate kinase, mitochondrial isoform X4 [KO:K00940] [EC:2.7.4.6]
105737507  NME1; nucleoside diphosphate kinase A [KO:K00940] [EC:2.7.4.6]
100592128  nucleoside diphosphate kinase B [KO:K00940] [EC:2.7.4.6]
100596874  NME3; nucleoside diphosphate kinase 3 isoform X1 [KO:K00940] [EC:2.7.4.6]
100580218  NME7; nucleoside diphosphate kinase 7 isoform X1 [KO:K00940] [EC:2.7.4.6]
115837088  nucleoside diphosphate kinase B-like isoform X1 [KO:K00940] [EC:2.7.4.6]
100604789  DUT; deoxyuridine 5'-triphosphate nucleotidohydrolase, mitochondrial [KO:K01520] [EC:3.6.1.23]
100606582  MPO; myeloperoxidase [KO:K10789] [EC:1.11.2.2]
100580331  NAT1; arylamine N-acetyltransferase 1 [KO:K00622] [EC:2.3.1.5]
100580987  NAT2; arylamine N-acetyltransferase 2 [KO:K00622] [EC:2.3.1.5]
100594173  cytochrome P450 2E1 [KO:K07415] [EC:1.14.14.-]
100604706  GSTO1; glutathione S-transferase omega-1 [KO:K00799] [EC:2.5.1.18]
100606364  GSTO2; glutathione S-transferase omega-2 [KO:K00799] [EC:2.5.1.18]
100583420  GSTA4; glutathione S-transferase A4 [KO:K00799] [EC:2.5.1.18]
100584415  glutathione S-transferase A1 isoform X1 [KO:K00799] [EC:2.5.1.18]
100583757  glutathione S-transferase A3 isoform X1 [KO:K00799] [EC:2.5.1.18]
100584083  glutathione S-transferase A5 [KO:K00799] [EC:2.5.1.18]
100606903  glutathione S-transferase omega-1-like isoform X2 [KO:K00799] [EC:2.5.1.18]
100589494  glutathione S-transferase theta-2B [KO:K00799] [EC:2.5.1.18]
100590747  glutathione S-transferase theta-4 [KO:K00799] [EC:2.5.1.18]
100597491  MGST2; microsomal glutathione S-transferase 2 isoform X2 [KO:K00799] [EC:2.5.1.18]
100603656  MGST1; microsomal glutathione S-transferase 1 [KO:K00799] [EC:2.5.1.18]
100582253  glutathione S-transferase theta-1 isoform X1 [KO:K00799] [EC:2.5.1.18]
100588847  GSTM3; glutathione S-transferase mu 3 [KO:K00799] [EC:2.5.1.18]
100586279  GSTM4; glutathione S-transferase Mu 4 isoform X1 [KO:K00799] [EC:2.5.1.18]
100587851  GSTM1; glutathione S-transferase Mu 1 isoform X2 [KO:K00799] [EC:2.5.1.18]
100587060  GSTM2; glutathione S-transferase Mu 2 [KO:K00799] [EC:2.5.1.18]
100593636  MGST3; microsomal glutathione S-transferase 3 [KO:K00799] [EC:2.5.1.18]
115830401  GSTM5; LOW QUALITY PROTEIN: glutathione S-transferase Mu 5 [KO:K00799] [EC:2.5.1.18]
115835864  LOW QUALITY PROTEIN: glutathione S-transferase theta-3-like [KO:K00799] [EC:2.5.1.18]
100583601  glutathione S-transferase theta-4-like [KO:K00799] [EC:2.5.1.18]
100580544  glutathione S-transferase P [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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