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Pathway Description
Ethambutol Action Pathway
Homo sapiens
Drug Action Pathway
Created: 2025-08-20
Last Updated: 2025-10-02
Ethambutol is a bacteriostatic antitubercular agent whose primary action targets the unique mycobacterial cell wall. After entering Mycobacterium tuberculosis cells, ethambutol specifically inhibits arabinosyltransferase enzymes (encoded by the embA, embB, and embC genes), which are essential for the polymerization of arabinogalactan and lipoarabinomannan, two major cell wall components. This inhibition disrupts the biosynthesis of arabinogalactan, undermining the structural integrity of the cell wall and significantly increasing its permeability. Decreased arabinogalactan synthesis also results in reduced anchoring sites for mycolic acids, impairing the stability of the mycolyl-arabinogalactan–peptidoglycan complex that protects the cell.
References
Ethambutol Pathway References
Mohammadnabi N, Shamseddin J, Emadi M, Bodaghi AB, Varseh M, Shariati A, Rezaei M, Dastranj M, Farahani A: Mycobacterium tuberculosis: The Mechanism of Pathogenicity, Immune Responses, and Diagnostic Challenges. J Clin Lab Anal. 2024 Dec;38(23):e25122. doi: 10.1002/jcla.25122. Epub 2024 Nov 26.
Pubmed: 39593272
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Repasy T, Lee J, Marino S, Martinez N, Kirschner DE, Hendricks G, Baker S, Wilson AA, Kotton DN, Kornfeld H: Intracellular bacillary burden reflects a burst size for Mycobacterium tuberculosis in vivo. PLoS Pathog. 2013 Feb;9(2):e1003190. doi: 10.1371/journal.ppat.1003190. Epub 2013 Feb 21.
Pubmed: 23436998
https://go.drugbank.com/drugs/DB00330
Bulut Y, Faure E, Thomas L, Equils O, Arditi M: Cooperation of Toll-like receptor 2 and 6 for cellular activation by soluble tuberculosis factor and Borrelia burgdorferi outer surface protein A lipoprotein: role of Toll-interacting protein and IL-1 receptor signaling molecules in Toll-like receptor 2 signaling. J Immunol. 2001 Jul 15;167(2):987-94. doi: 10.4049/jimmunol.167.2.987.
Pubmed: 11441107
Triantafilou M, Gamper FG, Haston RM, Mouratis MA, Morath S, Hartung T, Triantafilou K: Membrane sorting of toll-like receptor (TLR)-2/6 and TLR2/1 heterodimers at the cell surface determines heterotypic associations with CD36 and intracellular targeting. J Biol Chem. 2006 Oct 13;281(41):31002-11. doi: 10.1074/jbc.M602794200. Epub 2006 Jul 31.
Pubmed: 16880211
Drage MG, Pecora ND, Hise AG, Febbraio M, Silverstein RL, Golenbock DT, Boom WH, Harding CV: TLR2 and its co-receptors determine responses of macrophages and dendritic cells to lipoproteins of Mycobacterium tuberculosis. Cell Immunol. 2009;258(1):29-37. doi: 10.1016/j.cellimm.2009.03.008. Epub 2009 Apr 11.
Pubmed: 19362712
Asao H, Sasaki Y, Arita T, Tanaka N, Endo K, Kasai H, Takeshita T, Endo Y, Fujita T, Sugamura K: Hrs is associated with STAM, a signal-transducing adaptor molecule. Its suppressive effect on cytokine-induced cell growth. J Biol Chem. 1997 Dec 26;272(52):32785-91. doi: 10.1074/jbc.272.52.32785.
Pubmed: 9407053
Lu L, Komada M, Kitamura N: Human Hrs, a tyrosine kinase substrate in growth factor-stimulated cells: cDNA cloning and mapping of the gene to chromosome 17. Gene. 1998 Jun 15;213(1-2):125-32. doi: 10.1016/s0378-1119(98)00184-x.
Pubmed: 9630564
Scoles DR, Huynh DP, Chen MS, Burke SP, Gutmann DH, Pulst SM: The neurofibromatosis 2 tumor suppressor protein interacts with hepatocyte growth factor-regulated tyrosine kinase substrate. Hum Mol Genet. 2000 Jul 1;9(11):1567-74. doi: 10.1093/hmg/9.11.1567.
Pubmed: 10861283
Hoornaert I, Marynen P, Goris J, Sciot R, Baens M: MAPK phosphatase DUSP16/MKP-7, a candidate tumor suppressor for chromosome region 12p12-13, reduces BCR-ABL-induced transformation. Oncogene. 2003 Oct 30;22(49):7728-36. doi: 10.1038/sj.onc.1207089.
Pubmed: 14586399
Masuda K, Shima H, Watanabe M, Kikuchi K: MKP-7, a novel mitogen-activated protein kinase phosphatase, functions as a shuttle protein. J Biol Chem. 2001 Oct 19;276(42):39002-11. doi: 10.1074/jbc.M104600200. Epub 2001 Aug 6.
Pubmed: 11489891
Nagase T, Kikuno R, Hattori A, Kondo Y, Okumura K, Ohara O: Prediction of the coding sequences of unidentified human genes. XIX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. DNA Res. 2000 Dec 31;7(6):347-55. doi: 10.1093/dnares/7.6.347.
Pubmed: 11214970
Bloch KD, Wolfram JR, Brown DM, Roberts JD Jr, Zapol DG, Lepore JJ, Filippov G, Thomas JE, Jacob HJ, Bloch DB: Three members of the nitric oxide synthase II gene family (NOS2A, NOS2B, and NOS2C) colocalize to human chromosome 17. Genomics. 1995 Jun 10;27(3):526-30. doi: 10.1006/geno.1995.1086.
Pubmed: 7558036
Sherman PA, Laubach VE, Reep BR, Wood ER: Purification and cDNA sequence of an inducible nitric oxide synthase from a human tumor cell line. Biochemistry. 1993 Nov 2;32(43):11600-5. doi: 10.1021/bi00094a017.
Pubmed: 7692964
Geller DA, Lowenstein CJ, Shapiro RA, Nussler AK, Di Silvio M, Wang SC, Nakayama DK, Simmons RL, Snyder SH, Billiar TR: Molecular cloning and expression of inducible nitric oxide synthase from human hepatocytes. Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3491-5. doi: 10.1073/pnas.90.8.3491.
Pubmed: 7682706
Chi NC, Adam EJ, Adam SA: Sequence and characterization of cytoplasmic nuclear protein import factor p97. J Cell Biol. 1995 Jul;130(2):265-74. doi: 10.1083/jcb.130.2.265.
Pubmed: 7615630
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Pubmed: 7627554
Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. doi: 10.1038/ng1285. Epub 2003 Dec 21.
Pubmed: 14702039
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