ENTRY ko00983 Pathway NAME Drug metabolism - other enzymes CLASS Metabolism; Xenobiotics biodegradation and metabolism PATHWAY_MAP ko00983 Drug metabolism - other enzymes ORTHOLOGY K00760 hypoxanthine phosphoribosyltransferase [EC:2.4.2.8] K00088 IMP dehydrogenase [EC:1.1.1.205] K01951 GMP synthase (glutamine-hydrolysing) [EC:6.3.5.2] K00569 thiopurine S-methyltransferase [EC:2.1.1.67] K00106 xanthine dehydrogenase/oxidase [EC:1.17.1.4 1.17.3.2] K01519 XTP/dITP diphosphohydrolase [EC:3.6.1.66] K01044 carboxylesterase 1 [EC:3.1.1.1] K03927 carboxylesterase 2 [EC:3.1.1.1 3.1.1.84 3.1.1.56] K00699 glucuronosyltransferase [EC:2.4.1.17] K01195 beta-glucuronidase [EC:3.2.1.31] K17689 cytochrome P450 family 3 subfamily A4 [EC:1.14.13.32 1.14.14.55 1.14.14.56 1.14.14.57 1.14.14.73 1.14.14.-] K01489 cytidine deaminase [EC:3.5.4.5] K00758 thymidine phosphorylase [EC:2.4.2.4] K00207 dihydropyrimidine dehydrogenase (NADP+) [EC:1.3.1.2] K01464 dihydropyrimidinase [EC:3.5.2.2] K01431 beta-ureidopropionase [EC:3.5.1.6] K17683 cytochrome P450 family 2 subfamily A6 [EC:1.14.14.-] K00757 uridine phosphorylase [EC:2.4.2.3] K00876 uridine kinase [EC:2.7.1.48] K00857 thymidine kinase [EC:2.7.1.21] K13421 uridine monophosphate synthetase [EC:2.4.2.10 4.1.1.23] K13800 UMP-CMP kinase [EC:2.7.4.14] K10807 ribonucleoside-diphosphate reductase subunit M1 [EC:1.17.4.1] K10808 ribonucleoside-diphosphate reductase subunit M2 [EC:1.17.4.1] K00940 nucleoside-diphosphate kinase [EC:2.7.4.6] K01520 dUTP diphosphatase [EC:3.6.1.23] K03782 catalase-peroxidase [EC:1.11.1.21] K10789 myeloperoxidase [EC:1.11.2.2] K00622 arylamine N-acetyltransferase [EC:2.3.1.5] K07415 cytochrome P450 family 2 subfamily E1 [EC:1.14.14.-] K00799 glutathione S-transferase [EC:2.5.1.18] K23790 glutathione S-transferase P [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 PMID:15788214 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 PMID:16048561 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 PMID:16880012 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 PMID:15514566 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 PMID:10976516 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 PMID:15173095 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 PMID:11489791 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 PMID:11379777 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 PMID:24281184 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 PMID:27709007 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 PMID:27232112 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 PMID:20195289 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 PMID:20434429 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 PMID:26867495 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 PMID:22846601 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 PMID:12069966 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 PMID:17636923 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 ///