KEGG   PATHWAY: hsa00983Help
Entry
hsa00983                    Pathway                                

Name
Drug metabolism - other enzymes - Homo sapiens (human)
Class
Metabolism; Xenobiotics biodegradation and metabolism
BRITE hierarchy
Pathway map
hsa00983  Drug metabolism - other enzymes
hsa00983

Ortholog table
Disease
H00193  Dihydropyrimidine dehydrogenase deficiency
H00199  Dihydropyrimidinase deficiency
H00200  Beta-ureidopropionase deficiency
H00964  Thiopurine S-methyltransferase deficiency (TPMT deficiency)
Drug
D01206  Febuxostat (JAN/USAN/INN)
D01846  Gimeracil (JAN/INN)
D02365  Oxypurinol (USAN)
D03998  Eniluracil (USAN/INN)
Organism
Homo sapiens (human) [GN:hsa]
Gene
3251  HPRT1; hypoxanthine phosphoribosyltransferase 1 [KO:K00760] [EC:2.4.2.8]
3614  IMPDH1; inosine monophosphate dehydrogenase 1 [KO:K00088] [EC:1.1.1.205]
3615  IMPDH2; inosine monophosphate dehydrogenase 2 [KO:K00088] [EC:1.1.1.205]
8833  GMPS; guanine monophosphate synthase [KO:K01951] [EC:6.3.5.2]
7172  TPMT; thiopurine S-methyltransferase [KO:K00569] [EC:2.1.1.67]
7498  XDH; xanthine dehydrogenase [KO:K00106] [EC:1.17.3.2 1.17.1.4]
3704  ITPA; inosine triphosphatase [KO:K01519] [EC:3.6.1.-]
1066  CES1; carboxylesterase 1 [KO:K01044] [EC:3.1.1.1]
8824  CES2; carboxylesterase 2 [KO:K03927] [EC:3.1.1.56 3.1.1.84 3.1.1.1]
10941  UGT2A1; UDP glucuronosyltransferase family 2 member A1 complex locus [KO:K00699] [EC:2.4.1.17]
79799  UGT2A3; UDP glucuronosyltransferase family 2 member A3 [KO:K00699] [EC:2.4.1.17]
7367  UGT2B17; UDP glucuronosyltransferase family 2 member B17 [KO:K00699] [EC:2.4.1.17]
10720  UGT2B11; UDP glucuronosyltransferase family 2 member B11 [KO:K00699] [EC:2.4.1.17]
54490  UGT2B28; UDP glucuronosyltransferase family 2 member B28 [KO:K00699] [EC:2.4.1.17]
54578  UGT1A6; UDP glucuronosyltransferase family 1 member A6 [KO:K00699] [EC:2.4.1.17]
54657  UGT1A4; UDP glucuronosyltransferase family 1 member A4 [KO:K00699] [EC:2.4.1.17]
54658  UGT1A1; UDP glucuronosyltransferase family 1 member A1 [KO:K00699] [EC:2.4.1.17]
54659  UGT1A3; UDP glucuronosyltransferase family 1 member A3 [KO:K00699] [EC:2.4.1.17]
7365  UGT2B10; UDP glucuronosyltransferase family 2 member B10 [KO:K00699] [EC:2.4.1.17]
54600  UGT1A9; UDP glucuronosyltransferase family 1 member A9 [KO:K00699] [EC:2.4.1.17]
7364  UGT2B7; UDP glucuronosyltransferase family 2 member B7 [KO:K00699] [EC:2.4.1.17]
54575  UGT1A10; UDP glucuronosyltransferase family 1 member A10 [KO:K00699] [EC:2.4.1.17]
54576  UGT1A8; UDP glucuronosyltransferase family 1 member A8 [KO:K00699] [EC:2.4.1.17]
54579  UGT1A5; UDP glucuronosyltransferase family 1 member A5 [KO:K00699] [EC:2.4.1.17]
7366  UGT2B15; UDP glucuronosyltransferase family 2 member B15 [KO:K00699] [EC:2.4.1.17]
54577  UGT1A7; UDP glucuronosyltransferase family 1 member A7 [KO:K00699] [EC:2.4.1.17]
7363  UGT2B4; UDP glucuronosyltransferase family 2 member B4 [KO:K00699] [EC:2.4.1.17]
574537  UGT2A2; UDP glucuronosyltransferase family 2 member A2 [KO:K00699] [EC:2.4.1.17]
2990  GUSB; glucuronidase beta [KO:K01195] [EC:3.2.1.31]
1576  CYP3A4; cytochrome P450 family 3 subfamily A member 4 [KO:K17689] [EC:1.14.13.- 1.14.14.57 1.14.14.56 1.14.14.55 1.14.13.32]
978  CDA; cytidine deaminase [KO:K01489] [EC:3.5.4.5]
1890  TYMP; thymidine phosphorylase [KO:K00758] [EC:2.4.2.4]
1806  DPYD; dihydropyrimidine dehydrogenase [KO:K00207] [EC:1.3.1.2]
1807  DPYS; dihydropyrimidinase [KO:K01464] [EC:3.5.2.2]
51733  UPB1; beta-ureidopropionase 1 [KO:K01431] [EC:3.5.1.6]
1548  CYP2A6; cytochrome P450 family 2 subfamily A member 6 [KO:K17683] [EC:1.14.13.-]
151531  UPP2; uridine phosphorylase 2 [KO:K00757] [EC:2.4.2.3]
7378  UPP1; uridine phosphorylase 1 [KO:K00757] [EC:2.4.2.3]
83549  UCK1; uridine-cytidine kinase 1 [KO:K00876] [EC:2.7.1.48]
7371  UCK2; uridine-cytidine kinase 2 [KO:K00876] [EC:2.7.1.48]
54963  UCKL1; uridine-cytidine kinase 1 like 1 [KO:K00876] [EC:2.7.1.48]
7084  TK2; thymidine kinase 2, mitochondrial [KO:K00857] [EC:2.7.1.21]
7083  TK1; thymidine kinase 1 [KO:K00857] [EC:2.7.1.21]
7372  UMPS; uridine monophosphate synthetase [KO:K13421] [EC:4.1.1.23 2.4.2.10]
51727  CMPK1; cytidine/uridine monophosphate kinase 1 [KO:K13800] [EC:2.7.4.14]
6240  RRM1; ribonucleotide reductase catalytic subunit M1 [KO:K10807] [EC:1.17.4.1]
50484  RRM2B; ribonucleotide reductase regulatory TP53 inducible subunit M2B [KO:K10808] [EC:1.17.4.1]
6241  RRM2; ribonucleotide reductase regulatory subunit M2 [KO:K10808] [EC:1.17.4.1]
10201  NME6; NME/NM23 nucleoside diphosphate kinase 6 [KO:K00940] [EC:2.7.4.6]
29922  NME7; NME/NM23 family member 7 [KO:K00940] [EC:2.7.4.6]
4831  NME2; NME/NM23 nucleoside diphosphate kinase 2 [KO:K00940] [EC:2.7.4.6]
4833  NME4; NME/NM23 nucleoside diphosphate kinase 4 [KO:K00940] [EC:2.7.4.6]
4830  NME1; NME/NM23 nucleoside diphosphate kinase 1 [KO:K00940] [EC:2.7.4.6]
4832  NME3; NME/NM23 nucleoside diphosphate kinase 3 [KO:K00940] [EC:2.7.4.6]
654364  NME1-NME2; NME1-NME2 readthrough [KO:K00940] [EC:2.7.4.6]
1854  DUT; deoxyuridine triphosphatase [KO:K01520] [EC:3.6.1.23]
4353  MPO; myeloperoxidase [KO:K10789] [EC:1.11.2.2]
10  NAT2; N-acetyltransferase 2 [KO:K00622] [EC:2.3.1.5]
9  NAT1; N-acetyltransferase 1 [KO:K00622] [EC:2.3.1.5]
1571  CYP2E1; cytochrome P450 family 2 subfamily E member 1 [KO:K07415] [EC:1.14.13.-]
221357  GSTA5; glutathione S-transferase alpha 5 [KO:K00799] [EC:2.5.1.18]
2939  GSTA2; glutathione S-transferase alpha 2 [KO:K00799] [EC:2.5.1.18]
2941  GSTA4; glutathione S-transferase alpha 4 [KO:K00799] [EC:2.5.1.18]
119391  GSTO2; glutathione S-transferase omega 2 [KO:K00799] [EC:2.5.1.18]
2948  GSTM4; glutathione S-transferase mu 4 [KO:K00799] [EC:2.5.1.18]
2953  GSTT2; glutathione S-transferase theta 2 (gene/pseudogene) [KO:K00799] [EC:2.5.1.18]
2952  GSTT1; glutathione S-transferase theta 1 [KO:K00799] [EC:2.5.1.18]
2947  GSTM3; glutathione S-transferase mu 3 [KO:K00799] [EC:2.5.1.18]
4257  MGST1; microsomal glutathione S-transferase 1 [KO:K00799] [EC:2.5.1.18]
4259  MGST3; microsomal glutathione S-transferase 3 [KO:K00799] [EC:2.5.1.18]
2950  GSTP1; glutathione S-transferase pi 1 [KO:K00799] [EC:2.5.1.18]
2944  GSTM1; glutathione S-transferase mu 1 [KO:K00799] [EC:2.5.1.18]
2949  GSTM5; glutathione S-transferase mu 5 [KO:K00799] [EC:2.5.1.18]
4258  MGST2; microsomal glutathione S-transferase 2 [KO:K00799] [EC:2.5.1.18]
2938  GSTA1; glutathione S-transferase alpha 1 [KO:K00799] [EC:2.5.1.18]
2946  GSTM2; glutathione S-transferase mu 2 [KO:K00799] [EC:2.5.1.18]
2940  GSTA3; glutathione S-transferase alpha 3 [KO:K00799] [EC:2.5.1.18]
9446  GSTO1; glutathione S-transferase omega 1 [KO:K00799] [EC:2.5.1.18]
653689  GSTT2B; glutathione S-transferase theta 2B (gene/pseudogene) [KO:K00799] [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/USAN/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)
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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