Skip to main content
SpringerLink
Log in

Metabolism of leukotrienes

  • Review
  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Summary

The in vitro metabolism of leukotriene B4 is initiated by ω-hydroxylation. This reaction is followed by oxidation of the ω-hydroxyl group to a carboxyl group. In vivo extensive β-oxidation occurs and the main excreted products after administration of leukotriene B4 are water and carbon dioxide.

Experiments performed in vitro and in vivo have demonstrated that a major pathway of metabolism of the glutathione containing leukotrienes involves modifications of the tripeptide substituent. The metabolic alterations are initiated by enzymatic elimination of the N-terminal y-glutamyl residue, catalyzed by the enzyme γ-glutamyl transferase. This reaction is followed by hydrolysis of the remaining peptide bond resulting in elimination of the C-terminal glycine residue. The enzyme catalyzing the latter reaction is a membrane bound dipeptidase which occurs in kidney and other tissues. The product formed by these reactions, leukotriene E4, has been tentatively identified as a urinary metabolite in man following intravenous administration of leukotriene C4. In rats, the two major fecal metabolities of leukotriene C44 were characterized as being N-acetyl leukotriene E4 and N-acetyl 11-trans leukotriene E4. These compounds are formed in reactions between leukotriene E4 or 11-trans leukotriene E4 and acetyl coenzyme A. The reactions are catalyzed by a membrane bound enzyme present in liver, kidney and other tissues.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Hammarström S: Annu Rev Biochem 52:355–377, 1983.

    Google Scholar 

  2. Hammarström S: In: Litwack G (ed) Biochemical Actions of Hormones. Vol. 11. Academic Press. New York. 1984. pp 1–23.

    Google Scholar 

  3. Borgeat P, Samuelsson B: Proc Natl Acad Sci USA 76:3213–3217, 1979.

    Google Scholar 

  4. Rådmark O, Shimizu T, Jörnvall H, Samuelsson B: J Biol Chem 259:12339–12345, 1984.

    Google Scholar 

  5. Evans J, Dupuis P, Ford-Hutchinson A: Biochem Biophys Acta 840:43–50, 1985.

    Google Scholar 

  6. Hammock B, Moody D, Sevanian A: In: Law J and Rilling H (eds) Methods in Enzymology. Vol. 111. Academic Press. New York, 1985. pp 303–311.

    Google Scholar 

  7. Fitzpatrick F, Haeggström J, Granström E, Samuelsson B: Proc Natl Acad Sci USA 80:5425–5429, 1983.

    Google Scholar 

  8. Fitzpatrick F, Ligget W McGee J, Bunting S, Morton D, Samuelsson B: J Biol Chem 259:11403–11407, 1984.

    Google Scholar 

  9. Bosterling B, TrudellJ: Biochem Biophys Res Commun 115:995–1001, 1983.

    Google Scholar 

  10. Jakschik B, Harper T, Murphy R: J Biol Chem 257:5346–5349, 1982

    Google Scholar 

  11. Bach M, Brashler J, Morton D: Arch Biochem Biophys 230:455–465, 1984.

    Google Scholar 

  12. Söderström M, Mannervik B, Örning L, Hammarström S: Biochem Biophys Res Commun 128:265–270, 1985.

    Google Scholar 

  13. Mannervik B, Jensson H, Alin P, Örning L, Hammarström S: FEBS Lett 175:289–293, 1984.

    Google Scholar 

  14. Hansson G, Lindgren J-A, Dahle'n S-E, Hedqvist P, Samuelsson B: FEBS Lett 130:107–112, 1981.

    Google Scholar 

  15. Nadeau M, Fruteau de Laclos B, Picard S, Braquet P, Corey EJ Borgeat P: Can J Biochem Cell Biol. 62:1321–1326, 1984.

    Google Scholar 

  16. Powell WS: J Biol Chem 259:3082–3089, 1984.

    Google Scholar 

  17. Shak S, Goldstein I: J Biol Chem 259:10181–10187, 1984.

    Google Scholar 

  18. Shak S, Goldstein I: Biochem Biophys Res Commun 123:475–481, 1984.

    Google Scholar 

  19. Bosterling B, Trudell J: Biochem Biophys Res Commun 114:850–854, 1983.

    Google Scholar 

  20. Newton J, Eckardt R, Bender P, Leonard T, Straub K: Biochem Biophys Res Commun 128:733–738, 1985

    Google Scholar 

  21. Sumimoto H, Takeshige K, Sakai H, Minakami S: Biochem Biophys Res Commun 125:615–621, 1984

    Google Scholar 

  22. Maas R, Brash A, Oates J: In: Samuelsson B, Paoletti R (eds) Advances in Prostaglandin, Thromboxane, and Leukotriene Research Vol 9 Raven Press New York, 1982, pp 29–44.

    Google Scholar 

  23. Örning L, Hammarström S, Samuelsson B: Proc Natl Acad Sci USA 77:2014–2017. 1980.

    Google Scholar 

  24. Morris H, Taylor G, Piper P, Samhoun M, Tippins J: Prostaglandins 19:185–201, 1980.

    Google Scholar 

  25. Örning L, Hammarström S: J Biol Chem 255:8023–8026, 1980.

    Google Scholar 

  26. TateS: In: Jacoby W (ed) Enzymatic Basis of Detoxication. Vol 2. Academic Press New York, 1980. pp 97–120.

    Google Scholar 

  27. Meister A, Tate S, Ross L: In: Martonosi A (ed) The Enzymes of Biological Membranes. Vol 3. Plenum Publishing Corporation. New York, 1976. pp 315–347.

    Google Scholar 

  28. Örning L, Bernström K, Hammarström S: Eur J Biochem 120:41–45, 1981.

    Google Scholar 

  29. Tate S, Meister A: Proc Natl Acad Sci USA 75:4806–4809, 1978.

    Google Scholar 

  30. Reed D, Ellis W, Meek R: Biochem Biophys Res Commun 94:1273–1277, 1980.

    Google Scholar 

  31. Andersson M, Allison D, Meister A: Proc Natl Acad Sci USA 79:1088–1091, 1982.

    Google Scholar 

  32. Örning L, Hammarström S: Biochem Biophys Res Commun 106:1304–1309, 1982.

    Google Scholar 

  33. Hammarström S: J Biol Chem 256:9573–9578, 1981.

    Google Scholar 

  34. Bernström K, Hammarström S: J Biol Chem 256:9579–9582, 1981.

    Google Scholar 

  35. Kuo C, Lewis M, Jakschik B: Prostaglandins 28:929–938, 1984.

    Google Scholar 

  36. Orange R, Chang PL: J Immunol 115:1072–1077, 1975.

    Google Scholar 

  37. Orange R, Moore E: J Immunol 116:392–397, 1976.

    Google Scholar 

  38. Sok DE, PaiJ-K, Atrache V, Sih C: Proc Natl Acad Sci USA 77:6481–6485, 1980.

    Google Scholar 

  39. Yokota K, Shono F, YamamotoS, Kominami E, Katunuma N: J Biochem 94:1173–1178, 1983.

    Google Scholar 

  40. Lee C, Lewis R, Corey EJ, Austen KF: Immunol 48:27–35, 1983.

    Google Scholar 

  41. Houglum J, Pai J-K, Atrache V, Sok D-E, Sih C: Proc Natl Acad Sci USA 77:5688–5692, 1980.

    Google Scholar 

  42. Lewis R, DrazenJ, Austen KIT, Clark D, Corey EJ: Biochem Biophys Res Commun 96:271–277, 1980.

    Google Scholar 

  43. Dahle'n S-E, Hansson G, Hedquist P, Björk T, Granström E, Dahle'n B: Proc Natl Acad Sci USA 80:1712–1716, 1983.

    Google Scholar 

  44. Parker C, Falkenheim S, Huber M: Prostaglandins 20:863–886, 1980.

    Google Scholar 

  45. Parker C, Koch D, Huber M, Falkenheim S: Prostaglandins 20:887–908, 1980.

    Google Scholar 

  46. Bernström K, Hammarström S: Biochem Biophys Res Commun 109:800–804, 1982.

    Google Scholar 

  47. Griffith O, Bridges R, Meister A: Proc Natl Acad Sci USA 78:2777–2781, 1981.

    Google Scholar 

  48. Bernström K, Hammarström S: Arch Biochem Biophys, in press, 1985.

  49. Ormstad K, Uehara N, Orrenius S, Örning L, Hammarström S: Biochem Biophys Res Commun 104:1434–1440, 1982.

    Google Scholar 

  50. Uehara N, Ormstad K, Örning L, Hammarström S: Biochem Biophys Acta 732:69–74, 1983.

    Google Scholar 

  51. Minato S: Arch Biochem Biophys 192:235–240, 1979.

    Google Scholar 

  52. Spector R, Goetzl E: Science 228:325–327, 1985.

    Google Scholar 

  53. Serafin W, Oates J, Hubbard W: Prostaglandins 27:899–911, 1984.

    Google Scholar 

  54. Appelgren L-E, Hammarström S: J Biol Chem 257:531–535, 1982.

    Google Scholar 

  55. Örning L, Noren E, Gustafsson B, Hammarström S: J Biol Chem, in press, 1985.

  56. Goetzl EJ: Biochem Biophys Res Commun 106:270–275, 1982.

    Google Scholar 

  57. Hendersson W, Klebanoff S: Biochem Biophys Res Commun 110:266–272, 1983.

    Google Scholar 

  58. Lee C, Lewis R, Tauber A, Mehrotra M, Corey EJ, Austen KF: J Biol Chem 258:15004–15010, 1983.

    Google Scholar 

  59. Hagmann W Denzlinger C, and Keppler D: FEBS Lett 180:309–313, 1985.

    Google Scholar 

  60. Hammarström S, Bernström K, Örning L, Dahle'n S-E, Hedqvist P, Smedegård G, Revenäs B: Biochem Biophys Res Commun 101:1109–1115, 1981.

    Google Scholar 

  61. Morris H, Taylor G, Piper P, Tippins J: Nature 285:104–106, 1980.

    Google Scholar 

  62. Sok D-E, Pai J-K, Atrache V, Kang Y-C, Sih C: Biochem Biophys Res Commun 101:222–229, 1981.

    Google Scholar 

  63. Beaubien B, Tippins J, Morris H: Biochem Biophys Res Commun 125:97–104, 1984.

    Google Scholar 

  64. Lewis R, Austen KF, Drazen J, Clark D, Marfat A, Corey EJ: Proc Natl Acad Sci USA 77:3710–3714, 1980.

    Google Scholar 

  65. Harper T, Westcott J, Voelkels N, Murphy RC: J Biol Chem 259:14437–14440, 1984.

    Google Scholar 

  66. Parker C, Koch D, Huber M, Falkenheim S: Biochem Biophys Res Commun 97:1038–1046, 1980.

    Google Scholar 

  67. Lewis R, Drazen J, Figueiredo J, Corey EJ, Austen KF: Int J Immunopharm 4:85–90, 1982.

    Google Scholar 

  68. Köller M, Schönfeld W, Knöller J, Bremm K-D, König W, Spur B, Crea A, Peters W: Biochem Biophys Acta 833:128–134, 1985.

    Google Scholar 

  69. Örning L, Kaijser L, Hammarström S: Biochem Biophys, Res Commun 130:214–220.

  70. Stetson P: Fed Proc Fed Am Soc Exp Biol 34:557, 1975.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Physiological Chemistry, Karolinska Institutet, P.O. Box 60400, S-10401, Stockholm, Sweden

    Sven Hammarström, Lars Örning & Kerstin Bernström

Authors
  1. Sven Hammarström
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lars Örning
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kerstin Bernström
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hammarström, S., Örning, L. & Bernström, K. Metabolism of leukotrienes. Mol Cell Biochem 69, 7–16 (1985). https://doi.org/10.1007/BF00225922

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00225922

Keywords

Search

Navigation