Encyclopedia of Molecular Pharmacology

Living Edition
| Editors: Stefan Offermanns, Walter Rosenthal


  • Motonao Nakamura
  • Takehiko YokomizoEmail author
Living reference work entry
DOI: https://doi.org/10.1007/978-3-030-21573-6_87-1



Leukotrienes (LTs) are produced by the enzymatic oxidation of arachidonic acid (AA) released from cellular membrane (Shimizu 2009; Nakamura and Shimizu 2011). The 5-lipoxygenase (5-LO) cascade is involved in the production of these lipid mediators. Structural differences divide leukotrienes into two groups: (i) leukotriene B4 (LTB4), which contains two hydroxy groups, and (ii) cysteinyl-leukotrienes (Cys-LTs), i.e., LTC4, LTD4, and LTE4, based on the cysteine residue in their structures. LTB4 is synthesized from AA through formation of LTA4. LTB4 is well-known as one of the potent chemoattractants and activators of leukocytes and is involved in inflammatory diseases. LTC4 is also produced via LTA4 by glutathione conjugation of LTA4 with opening of the epoxide at the allylic position C-6. Next, LTC4 is converted to LTD4 by elimination of glutamic acid. The remaining peptide bond in LTD4is further hydrolyzed by a dipeptidase to generate...

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  1. Hori T, Okuno T, Hirata K, Yamashita K, Kawano Y, Yamamoto M, Hato M, Nakamura M, Shimizu T, Yokomizo T, Miyano M, Yokoyama S (2018) Na(+)-mimicking ligands stabilize the inactive state of leukotriene B4 receptor BLT1. Nat Chem Biol 14(3):262–269.  https://doi.org/10.1038/nchembio.2547CrossRefPubMedGoogle Scholar
  2. Nakamura M, Shimizu T (2011) Leukotriene receptors. Chem Rev 111(10):6231–6298.  https://doi.org/10.1021/cr100392sCrossRefPubMedGoogle Scholar
  3. Shimizu T (2009) Lipid mediators in health and disease: enzymes and receptors as therapeutic targets for the regulation of immunity and inflammation. Annu Rev Pharmacol Toxicol 49:123–150.  https://doi.org/10.1146/annurev.pharmtox.011008.145616CrossRefPubMedGoogle Scholar
  4. Snelgrove RJ, Jackson PL, Hardison MT, Noerager BD, Kinloch A, Gaggar A, Shastry S, Rowe SM, Shim YM, Hussell T, Blalock JE (2010) A critical role for LTA4H in limiting chronic pulmonary neutrophilic inflammation. Science 330(6000):90–94.  https://doi.org/10.1126/science.1190594CrossRefPubMedPubMedCentralGoogle Scholar
  5. Yokomizo T, Izumi T, Takahashi T, Kasama T, Kobayashi Y, Sato F, Taketani Y, Shimizu T (1993) Enzymatic inactivation of leukotriene B4 by a novel enzyme found in the porcine kidney. Purification and properties of leukotriene B4 12-hydroxydehydrogenase. J Biol Chem 268(24):18128–18135PubMedGoogle Scholar
  6. Yokomizo T, Ogawa Y, Uozumi N, Kume K, Izumi T, Shimizu T (1996) cDNA cloning, expression, and mutagenesis study of leukotriene B4 12-hydroxydehydrogenase. J Biol Chem 271(5):2844–2850.  https://doi.org/10.1074/jbc.271.5.2844CrossRefPubMedGoogle Scholar
  7. Yokomizo T, Nakamura M, Shimizu T (2018) Leukotriene receptors as potential therapeutic targets. J Clin Invest 128(7):2691–2701.  https://doi.org/10.1172/JCI97946CrossRefPubMedPubMedCentralGoogle Scholar

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© Springer-Verlag Berlin Heidelberg New York 2020

Authors and Affiliations

  1. 1.Department of Life Science, Faculty of ScienceOkayama University of ScienceOkayamaJapan
  2. 2.Department of Biochemistry, Graduate School of MedicineJuntendo UniversityTokyoJapan