KEGG   PATHWAY: hsa00983Help
Entry
hsa00983                    Pathway                                

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

All organismsOrtholog 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.- 1.14.14.56 1.14.14.55 1.14.13.97 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
 

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