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Gene Review

LTA4H  -  leukotriene A4 hydrolase

Homo sapiens

Synonyms: LTA-4 hydrolase, LTA4, Leukotriene A(4) hydrolase, Leukotriene A-4 hydrolase
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Disease relevance of LTA4H


High impact information on LTA4H


Chemical compound and disease context of LTA4H


Biological context of LTA4H


Anatomical context of LTA4H


Associations of LTA4H with chemical compounds

  • Leukotriene (LT) A(4) hydrolase/aminopeptidase (LTA4H) is a bifunctional zinc enzyme that catalyzes the biosynthesis of LTB4, a potent lipid chemoattractant involved in inflammation, immune responses, host defense against infection, and PAF-induced shock [18].
  • The high resolution crystal structure of LTA4H in complex with the competitive inhibitor bestatin reveals a protein folded into three domains that together create a deep cleft harboring the catalytic Zn(2+) site [18].
  • Furthermore, expression of 5-LO and LTA4H, but not FLAP, is increased in patients with recent or ongoing symptoms of plaque instability, and medication with warfarin correlates with increased levels of FLAP mRNA [15].
  • To further examine the role of LTB4 in oral carcinogenesis, two LTA4H inhibitors, bestatin and SA6541, were evaluated in a long-term chemoprevention experiment [19].
  • From the crystal structure of LTA4H, a hydrophilic patch composed of Gln-134, Tyr-267, and Asp-375 was identified in a narrow and otherwise hydrophobic pocket, believed to bind LTA4 [20].

Regulatory relationships of LTA4H


Other interactions of LTA4H


Analytical, diagnostic and therapeutic context of LTA4H


  1. High-level expression and purification of human leukotriene A4 hydrolase from insect cells infected with a baculovirus vector. Gierse, J.K., Luckow, V.A., Askonas, L.J., Duffin, K.L., Aykent, S., Bild, G.S., Rodi, C.P., Sullivan, P.M., Bourner, M.J., Kimack, N.M. Protein Expr. Purif. (1993) [Pubmed]
  2. Leukotriene A4 hydrolase as a target for cancer prevention and therapy. Chen, X., Wang, S., Wu, N., Yang, C.S. Current cancer drug targets. (2004) [Pubmed]
  3. Cloning and characterization of the human leukotriene A4 hydrolase gene. Mancini, J.A., Evans, J.F. Eur. J. Biochem. (1995) [Pubmed]
  4. A variant of the gene encoding leukotriene A4 hydrolase confers ethnicity-specific risk of myocardial infarction. Helgadottir, A., Manolescu, A., Helgason, A., Thorleifsson, G., Thorsteinsdottir, U., Gudbjartsson, D.F., Gretarsdottir, S., Magnusson, K.P., Gudmundsson, G., Hicks, A., Jonsson, T., Grant, S.F., Sainz, J., O'Brien, S.J., Sveinbjornsdottir, S., Valdimarsson, E.M., Matthiasson, S.E., Levey, A.I., Abramson, J.L., Reilly, M.P., Vaccarino, V., Wolfe, M.L., Gudnason, V., Quyyumi, A.A., Topol, E.J., Rader, D.J., Thorgeirsson, G., Gulcher, J.R., Hakonarson, H., Kong, A., Stefansson, K. Nat. Genet. (2006) [Pubmed]
  5. Suppression of leukotriene B4 biosynthesis by endogenous adenosine in ligand-activated human neutrophils. Krump, E., Picard, S., Mancini, J., Borgeat, P. J. Exp. Med. (1997) [Pubmed]
  6. Neutrophil activation by anti-proteinase 3 antibodies in Wegener's granulomatosis: role of exogenous arachidonic acid and leukotriene B4 generation. Grimminger, F., Hattar, K., Papavassilis, C., Temmesfeld, B., Csernok, E., Gross, W.L., Seeger, W., Sibelius, U. J. Exp. Med. (1996) [Pubmed]
  7. Molecular cloning of the gene for human leukotriene C4 synthase. Organization, nucleotide sequence, and chromosomal localization to 5q35. Penrose, J.F., Spector, J., Baldasaro, M., Xu, K., Boyce, J., Arm, J.P., Austen, K.F., Lam, B.K. J. Biol. Chem. (1996) [Pubmed]
  8. Eosinophil 15-lipoxygenase is a leukotriene A4 synthase. MacMillan, D.K., Hill, E., Sala, A., Sigal, E., Shuman, T., Henson, P.M., Murphy, R.C. J. Biol. Chem. (1994) [Pubmed]
  9. The biology of 5-lipoxygenase: function, structure, and regulatory mechanisms. Silverman, E.S., Drazen, J.M. Proc. Assoc. Am. Physicians (1999) [Pubmed]
  10. Leukotriene A4 hydrolase in peripheral leukocytes of patients with atopic dermatitis. Okano-Mitani, H., Ikai, K., Imamura, S. Arch. Dermatol. Res. (1996) [Pubmed]
  11. Isolation and structure of leukotriene-A4 hydrolase inhibitor: 8(S)-amino-2(R)-methyl-7-oxononanoic acid produced by Streptomyces diastaticus. Parnas, B.L., Durley, R.C., Rhoden, E.E., Kilpatrick, B.F., Makkar, N., Thomas, K.E., Smith, W.G., Corley, D.G. J. Nat. Prod. (1996) [Pubmed]
  12. Leukotriene A4 hydrolase expression in PEL cells is regulated at the transcriptional level and leads to increased leukotriene B4 production. Arguello, M., Paz, S., Hernandez, E., Corriveau-Bourque, C., Fawaz, L.M., Hiscott, J., Lin, R. J. Immunol. (2006) [Pubmed]
  13. Molecular cloning and amino acid sequence of leukotriene A4 hydrolase. Funk, C.D., Rådmark, O., Fu, J.Y., Matsumoto, T., Jörnvall, H., Shimizu, T., Samuelsson, B. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  14. Regulation of leukotriene A4 hydrolase activity in endothelial cells by phosphorylation. Rybina, I.V., Liu, H., Gor, Y., Feinmark, S.J. J. Biol. Chem. (1997) [Pubmed]
  15. Expression of 5-lipoxygenase and leukotriene A4 hydrolase in human atherosclerotic lesions correlates with symptoms of plaque instability. Qiu, H., Gabrielsen, A., Agardh, H.E., Wan, M., Wetterholm, A., Wong, C.H., Hedin, U., Swedenborg, J., Hansson, G.K., Samuelsson, B., Paulsson-Berne, G., Haeggström, J.Z. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  16. Identification of regions of leukotriene C4 synthase which direct the enzyme to its nuclear envelope localization. Svartz, J., Hallin, E., Shi, Y., Söderström, M., Hammarström, S. J. Cell. Biochem. (2006) [Pubmed]
  17. Leukotriene A4 hydrolase in human leukocytes. Purification and properties. Rådmark, O., Shimizu, T., Jörnvall, H., Samuelsson, B. J. Biol. Chem. (1984) [Pubmed]
  18. Crystal structure of human leukotriene A(4) hydrolase, a bifunctional enzyme in inflammation. Thunnissen, M.M., Nordlund, P., Haeggström, J.Z. Nat. Struct. Biol. (2001) [Pubmed]
  19. Involvement of the 5-lipoxygenase/leukotriene A4 hydrolase pathway in 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral carcinogenesis in hamster cheek pouch, and inhibition of carcinogenesis by its inhibitors. Sun, Z., Sood, S., Li, N., Ramji, D., Yang, P., Newman, R.A., Yang, C.S., Chen, X. Carcinogenesis (2006) [Pubmed]
  20. Leukotriene A4 hydrolase: selective abrogation of leukotriene B4 formation by mutation of aspartic acid 375. Rudberg, P.C., Tholander, F., Thunnissen, M.M., Samuelsson, B., Haeggstrom, J.Z. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  21. Studies on the regulation and localization of 5-lipoxygenase in human B-lymphocytes. Jakobsson, P.J., Shaskin, P., Larsson, P., Feltenmark, S., Odlander, B., Aguilar-Santelises, M., Jondal, M., Biberfeld, P., Claesson, H.E. Eur. J. Biochem. (1995) [Pubmed]
  22. Isolation of human promoter regions by Alu repeat consensus-based polymerase chain reaction. Jendraschak, E., Kaminski, W.E. Genomics (1998) [Pubmed]
  23. Production of arachidonic acid metabolites by the colon adenocarcinoma cell line HT29 cl.19A and their effect on chloride secretion. Battu, S., Clement, G., Heyman, M., Wal, J.M., Cook-Moreau, J., Desjeux, J.F., Beneytout, J.L. Cancer Lett. (1997) [Pubmed]
  24. Leukotriene A4 hydrolase in rat and human esophageal adenocarcinomas and inhibitory effects of bestatin. Chen, X., Li, N., Wang, S., Wu, N., Hong, J., Jiao, X., Krasna, M.J., Beer, D.G., Yang, C.S. J. Natl. Cancer Inst. (2003) [Pubmed]
  25. The human leukotriene A4 hydrolase gene is expressed in two alternatively spliced mRNA forms. Jendraschak, E., Kaminski, W.E., Kiefl, R., von Schacky, C. Biochem. J. (1996) [Pubmed]
  26. Purification and characterization of leukotriene A4 hydrolase from human epidermis. Iversen, L., Kristensen, P., Nissen, J.B., Merrick, W.C., Kragballe, K. FEBS Lett. (1995) [Pubmed]
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