Enzymatic Formation of Leukotrienes

  • Barbara A. Jakschik
  • Christine G. Kuo
  • Yue Fang Wei
Part of the Prostaglandins, Leukotrienes, and Cancer book series (PLAC, volume 1)


Release of slow reacting substance (SRS) from guinea pig lung treated with cobra venom was described in 1938 (1) and release due to immunological challenge in 1940 (2). Characterization of SRS showed that it was a polar lipid with absorbance in the UV region and that it might contain sulfur (3–6). Work with labeled arachidonic acid indicated that this fatty acid is a metabolic precursor of SRS (7,8).


Calcium Ionophore A23187 Sucrose Pellet Eicosatrienoic Acid Eicosatetraenoic Acid Polyenoic Fatty Acid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Feldberg W, Kellaway CH: Liberation of histamine and formation of lysolecithin-like substances by cobra venom. J Physiol (Lond) (94): 187–226, 1938.PubMedGoogle Scholar
  2. 2.
    Kell away CH, Trethewie ER: Liberation of a slow reacting smooth muscle stimulating substance in anaphylaxis. J Exp Physiol (30): 121–145, 1940.Google Scholar
  3. 3.
    Strandberg K, Uvnas B.: Purification and properties of the slow reacting substance formed in the cat paw with compound 48/80. Acta Physiol Scand (82): 358–374, 1971.PubMedCrossRefGoogle Scholar
  4. 4.
    Orange RP, Murphy RC, Karnovsky ML, Austen KF: The physiochemical characteristics and purification of slow reacting substance of anaphylaxis. J Immunol (110): 760–770, 1973.PubMedGoogle Scholar
  5. 5.
    Morris HR, Taylor GW, Piper PJ, Sirois 0, Tippins JK: Slow-reacting substance of anaphylaxis. Purification and characteristics. FEBS Letters (87): 203–206, 1978.PubMedCrossRefGoogle Scholar
  6. 6.
    Parker CW, Jakschik BA, Huber MM, Falkenhein SF: Characterization of slow reacting substance as a family of thiolipids derived from arachidonic acid. Biochem Biophys Res Comm (89): 1186–1192, 1979.PubMedCrossRefGoogle Scholar
  7. 7.
    Jakschik BA, Falkenhein S, Parker CW: Precursor role of arachidonic acid in release of slow reacting substance from rat basophilic leukemia cells. Proc Natl Acad Sci USA (74): 4577–4581, 1977.PubMedCrossRefGoogle Scholar
  8. 8.
    Bach MK, Brashler JK, Gorman RR: On the structure of slow reacting substance of anaphylaxis: evidence for synthesis from arachidonic acid. Prostaglandins (14): 21–38, 1977.PubMedCrossRefGoogle Scholar
  9. 9.
    Borgeat P, Hamberg M, Samuelsson B: Transformation of arachidonic acid and homo-y-linolenic acid by rabbit polymorphonuclear leukocytes. J Biol Chem (251): 7816–7820, 1976.PubMedGoogle Scholar
  10. 10.
    Borgeat P, Samuelsson B: Transformation of arachidonic acid by rabbit polymorphonuclear leukocytes. Formation of a novel dihydroxy-eicosatetraenoic acid. J Biol Chem (254): 2643–2646, 1979.PubMedGoogle Scholar
  11. 11.
    Borgeat P, Samuelsson B: Metabolism of aracnidonic acid in polymorphonuclear leukocytes. Structural analysis of novel hydroxylated compounds. J Biol Chem (254): 7865–7869, 1979.PubMedGoogle Scholar
  12. 12.
    Borgeat P, Samuelsson B: Aracnidonic acid metabolism in polymorphonuclear leukocytes: Unstable intermediate in the formation of dihydroxy acids. Proc Natl Acad Sci USA (76): 3213–3217, 1979.PubMedCrossRefGoogle Scholar
  13. 13.
    Radmark O, Malmsten C, Samuelsson B, Clark DA, Giichi G, Marfat A, Corey EJ: Leukotriene A: Streochemistry and enzymatic conversion to leukotriene B. Biochem Biophys Res Comm (92): 954–961, 1980.PubMedCrossRefGoogle Scholar
  14. 14.
    Panossian A, Hamberg M, Samuelsson B: On the Mechanism of biosynthesis of leukotrienes and related compounds. FEBS Letters (150): 511–513, 1982.PubMedCrossRefGoogle Scholar
  15. 15.
    Bach MK, Brashler JR: In vivo and in vitro production of a slow reacting substance in tne rat upon treatment with calcium ionophore. J Immunol (113): 2040–2044, 1974.PubMedGoogle Scholar
  16. 16.
    Jakschik BA, Kulczycki A Jr, MacDonald HH, Parker CW: Release of slow reacting substance (SRS) from rat basophilic leukemia (RBL-1) cells. J Immunol (119): 618–623, 1977.PubMedGoogle Scholar
  17. 17.
    Murpny RC, Hammarstrom S, Samuelsson B: Leukotriene C: A slow reacting substance from murine mastocytoma cells. Proc Natl Acad Sci USA (76): 4275–4279, 1979.CrossRefGoogle Scholar
  18. 18.
    Hammarstrom S, Murphy RC, Samuelsson B, Clark DA, Mioskowski C, Corey EJ: Structure of leukotriene C: Identification of amino acid part. Biochem Biophys Res Comm (91): 1266–1272, 1979.PubMedCrossRefGoogle Scholar
  19. 19.
    Parker CW, Huber MM, Hoffman MK, Falkenhein SF: Characterization of two major species of slow reacting substance from rat basophilic leukemia cells as glutathionyl thioethers of eicosatetraenoic acid oxygenated at the 5-position. Evidence that peroxy groups are present and important for spasmogenic activity. Prostaglandins (18): 673–686, 1979.PubMedCrossRefGoogle Scholar
  20. 20.
    Morris HR, Taylor GW, Piper PJ, Tippens JR: Structure of slow reacting substance of anaphylaxis from guinea pig lung. Nature (285): 104–106, 1980.PubMedCrossRefGoogle Scholar
  21. 21.
    Parker CW, Falkenhein SF, Huber MM: Sequential conversion of the glutathionyl side chain of slow reacting substance (SRS) to cysteinyl-glycine and cysteine in rat basophilic leukemia cells stimulated with A23187. Prostaglandins (20): 863–887, 1980.PubMedCrossRefGoogle Scholar
  22. Sok DE, Pai JK, Atrache V, Kang YC, Sih CJ: Enzymatic inactivation of SRS-cys-gly (leukotriene D). Biochem Biophys Res Comm (101): 222–229.Google Scholar
  23. 23.
    Lewis RA, Drazen JM, Austen KF, Clark DA, Corey EJ: Identification of the C(6)-S-conjugate of leukotriene A with cysteine as a naturally occurring slow reacting substance of anaphylaxis (SRS-A). Importance of the 11-cis geometry for biologic activity. Biochem. Biophys Res Comm (96): 271–277, 1980.CrossRefGoogle Scholar
  24. 24.
    Hammarstrom S, Samuelsson B: Detection of leukotriene A4 as an intermediate in the biosynthesis of leukotriene C4 and D4. FEBS Letters (122): 83–85, 1980.CrossRefGoogle Scholar
  25. 25.
    Radmark O, Malmsten C, Samuelsson B: Leukotriene A4: Enzymatic conversion to leukotriene C4. Biochem Biophys Res Comm (96): 1679–1687, 1980.PubMedCrossRefGoogle Scholar
  26. 26.
    Jakschik BA, Lee LH, Shuffer G, Parker CW: Aracnidonic acid metabolism in rat basophilic leukemia (RBL-1) cells. Prostaglandins (16): 733–748, 1978.CrossRefGoogle Scholar
  27. 27.
    Borgeat P, Samuelsson B: Aracnidonic acid metabolism in polymorphonuclear leukocytes: Effects of ionophore A23187. Proc Natl Acad Sci USA (76): 2148–2152, 1979.PubMedCrossRefGoogle Scholar
  28. 28.
    Jakschik BA, Sun FF, Lee LH, Steinhoff MM: Calcium stimulation of a novel lipoxygenase. Biochem Biophys Res Comm (95): 103–110, 1980.PubMedCrossRefGoogle Scholar
  29. 29.
    Jakschik BA, Lee LH: Enzymatic assembly of slow reacting substance. Nature (287): 51–52, 1980.PubMedCrossRefGoogle Scholar
  30. 30.
    Ochi K, Yoshimoto T, Yamamato S: Arachidonate 5-lipoxygenase of guinea pig peritoneal polymorphonuclear leukocytes. J Biol Chem (258): 5754–5758, 1983.PubMedGoogle Scholar
  31. 31.
    Parker CW, Aykent S: Calcium stimulation of the 5-lipoxygenase from RBL-1 cells. Biochem Biophys Res Comm (109): 1011–1016, 1982.PubMedCrossRefGoogle Scholar
  32. 32.
    Parker CW, Koch D, Huber MM, Falkenhein SF: Incorporation of radiolabel from [1–14C]5-hydroperoxyeicosatetraenoic acid into slow reacting substance. Biochem Biophys Res Comm (94): 1037–1043, 1980.PubMedCrossRefGoogle Scholar
  33. 33.
    Jakschik BA, Kuo CG: Subcellular localization of leukotriene-forming enzymes. Adv Prostaglandin Thromboxane Leukotriene Res (11): 141–145, 1983.Google Scholar
  34. 34.
    Jakschik BA, Kuo CG: Characterization of Leukotrienes A4 and B4 biosynthesis. Prostaglandins (25): 767–782, 1983.PubMedCrossRefGoogle Scholar
  35. 35.
    Jakschik BA, Harper T, Murphy RC: Leukotriene C4 and D 4 formation by particulate enzymes. J Biol Chem (257): 5346–5349, 1982.PubMedGoogle Scholar
  36. 36.
    Egan RW, Tischler AN, Baptista EM, Ham EA, Soderman DD, Gale PH: Specific inhibition and oxidative regulation of 5-lipoxygenase. Adv Prostaglandin Thromboxane Leukotriene Res (11): 151–157, 1983.Google Scholar
  37. 37.
    Maycock AL, Anderson MS, DeSousa DM, Kuehl FA Jr: Leukotriene A4: Preparation and enzymatic conversion in a cell-free system to leukotriene B4. J Biol Chem (257): 13911–13914, 1982.PubMedGoogle Scholar
  38. Kuo CG, Lewis MT, Jakschik BA: Leukotriene D4 and E4 formation by plasma membrane bound enzymes (submitted).Google Scholar
  39. 39.
    Tate SS, Meister A: Serine-borate complex as a transition state inhibitor of γ-glutamyl transpeptidase. Proc Natl Acad Sci USA (75): 4806–4809, 1978.PubMedCrossRefGoogle Scholar
  40. 40.
    Örning L, Hammarström S: Inhibition of leukotriene C and leukotriene D biosynthesis. J Biol Chem (255): 8023–8026, 1980.PubMedGoogle Scholar
  41. 41.
    Sok DE, Pai JK, Atrache V, Sih CJ: Characterization of slow reacting substance (SRSs) of rat basophilic leukemia (RBL-1) cells: Effect of cysteine on SRS profile. Proc Natl Acad Sci USA (77): 6481–6485, 1980.PubMedCrossRefGoogle Scholar
  42. 42.
    Tate SS, Thompson GA, Meister A: Recent studies on y-glutamyl transpeptidase. In: Arias TM, Jakoby, WB (eds). Glutathione Metabolism and Function, Raven Press, New York, 1976, pp. 45–55.Google Scholar
  43. 43.
    Wolkoff AW, Weisiger RA, Jakoby WB: The multiple roles of glutathione transferases (ligandins) In: Popper H, Schaffner F (eds) Prog Liver Dis (6): 214–224, 1979.Google Scholar
  44. 44.
    Morgenstern R, Meyer J, DePierre JW, Ernster L: Characterization of rat-liver microsomal glutathione-S-transferase activity. Europ J Biochem (104): 167–174, 1980.PubMedCrossRefGoogle Scholar
  45. 45.
    Bach MK, Brashler JR, Morton DR: Solubilization and characterization of the leukotriene C4 synthetase of rat basophilic leukemia cells: A novelparticulate glutathione-S-transferase. Arch Biochem Biophys (230): in press, 1984.Google Scholar
  46. 46.
    Jakschik, BA, Kuo CG: Characterization of leukotriene formation. In: Charkrin LW, Bailey DM: The Leukotrienes, Academic Press, Inc. New York, 1984, pp. 141–164.Google Scholar
  47. 47.
    Jakschik BA, Sams AR, Sprecher H, Needleman P: Fatty acid structural requirements for leukotriene biosynthesis. Prostaglandins (20): 401–410, 1980.PubMedCrossRefGoogle Scholar
  48. 48.
    Needleman P, Wyche AA, LeDue LE, Jakschik BA, Sankarapa SK, Sprecher H: Fatty acids as sources of potential “magic bullets” for the modification of platelet and vascular function. Prog Lipid Res (20): 415–42, 1981.PubMedCrossRefGoogle Scholar
  49. 49.
    Jakschik BA, Morrison AR, Sprecher H: Products derived from 5,8,11-eicosatrienoic acid by the 5-lipoxygenase-leukotriene pathway. J Biol Chem (258): 12797–12000, 1983.PubMedGoogle Scholar
  50. 50.
    Hammarstrom S: Leukotriene C5: a slow reacting substance derived from eicosapentaenoic acid. J Biol Chem (255): 7093–7094, 1980.PubMedGoogle Scholar
  51. 51.
    Murphy RC, Pickett WC, Culp BR, Lands WEM: Tetraene and pentaene leukotrienes: Selective production from murine mastocytoma cells after dietary manipulation. Prostaglandins (22): 613–622, 1981.PubMedCrossRefGoogle Scholar
  52. 52.
    Hammarstrom S: Conversion of 5,8,11-eicosatrienoic acid to leukotrienes C4 and D4. J Biol Chem (256): 2275–2279, 1981.PubMedGoogle Scholar
  53. 53.
    Hammarstrom S: Conversion of dinomo-γ-linolenic acid to an isomer of leukotriene C3, oxygenated at C-8. J Biol Chem (256): 7712–7714, 1981.PubMedGoogle Scholar
  54. Wei YF, Evans RW, Morrison AR, Sprecher H, Jakschik BA: Double bond requirement for the 5-lipoxygenase pathway (submitted).Google Scholar
  55. 55.
    Jakschik BA, DiSantis DM, Sankarappa SK, Sprecher H: Modulation of leukotriene formation by various acetylenic acids. Adv Prostaglandin Thromboxane Leukotriene Res (9): 127–135, 1982.Google Scholar

Copyright information

© Martinus Nijhoff Publishing, Boston 1985

Authors and Affiliations

  • Barbara A. Jakschik
  • Christine G. Kuo
  • Yue Fang Wei

There are no affiliations available

Personalised recommendations