Phospholipases: Link Between Membrane Phospholipids and Arachidonate Metabolites

  • H. van den Bosch
Part of the NATO Advanced Science Institutes Series book series (NSSA, volume 54)


This paper deals with the relationship between phospholipid arachidonate and free arachidonate which constitutes the substrate for cyclo-oxygenase and lipoxygenase. The available evidence for the role of phospholipases in the release of arachidonate will be discussed with some emphasis on the possible regulation of this phospholipase activity.


Human Platelet Phosphatidic Acid Phospholipase Activity Platelet Phospholipid ARACHIDONATE Metabolism 
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.
    H. van den Bosch, Phosphoglyceride metabolism, Annu. Rev. Biochem. 43: 243 (1974).CrossRefGoogle Scholar
  2. 2.
    G.P.H. van Heusden and H. van den Bosch, The Influence of exogenous and membrane-bound phosphatidate concentration on the activity of CTP:phosphatidate cytidylyltransferase and phosphatidate phosphohydrolase, Eur. J. Biochem. 84:405 (1978).PubMedCrossRefGoogle Scholar
  3. 3.
    J.H.E. Moonen, P. Trienekens and H. van den Bosch, The action of purified lysophospholipases on microsomal membrane-bound lysophosphatidylcholine, Biochim. Biophys. Acta 489:423 (1977).Google Scholar
  4. 4.
    A.J. Marcus, H.L. Ullman and L.B. Safier, Lipid composition of subcellular particles of human blood platelets, J. Lipid Res. 10:108 (1969).PubMedGoogle Scholar
  5. 5.
    F. Possmayer, G.L. Scherphof, T.M.A.R. Dubbelman, L.M.G. van Golde and L.L.M. van Deenen, Positional specificity of saturated fatty acids in phosphatidic acid from rat liver, Biochim. Biophys. Acta 176:95 (1969).Google Scholar
  6. 6.
    S. Yamashita and S. Numa, Partial Purification and properties of glycerophosphate acyltransferase from rat liver, Eur. J. Biochem. 31:565 (1972).PubMedCrossRefGoogle Scholar
  7. 7.
    S. Yamashita, K. Hosaka and S. Numa, Resolution and reconstitution of the phosphatidate-synthesizing system of rat liver microsomes, Proc; Natl. Acad. Sci. USA 69:3490 (1972).CrossRefGoogle Scholar
  8. 8.
    S. Yamashita, N. Nakaya, Y. Míki and S. Numa, Separation of 1-acylglycerolphosphate acyltransferase and 1-acylglycerolphosphorylcholine acyltransferase of rat liver microsomes, Proc. Natl. Acad. Sci. USA 72:600 (1975).PubMedCrossRefGoogle Scholar
  9. 9.
    A. Derksen and P. Cohen, Patterns of fatty acid release from endogenous substrates by human platelets homogenates and membranes, J. Biol. Chem. 250:9342 (1975).PubMedGoogle Scholar
  10. 10.
    D.A. van Dorp, R.K. Beerthuis, D.H. Nugteren and H. Vonkeman, The biosynthesis of prostaglandins, Biochim. Biophys. Acta 90:204 (1964).Google Scholar
  11. 11.
    S. Bergström, H. Danielsson and B. Samuelsson, The enzymatic formation of prostaglandin E2 from arachidonic acid, Biochim. Biophys. Acta 90:207 (1964).Google Scholar
  12. 12.
    W. Vogt, Role of phospholipase A2 in prostaglandin formation, in: “Advances in prostaglandin and thromboxane research”, C. Galli et al., ed., Raven Press, New York, p. 89 (1978).Google Scholar
  13. 13.
    W.E.M. Lands and B. Samuelsson, Phospholipid precursors of prostaglandins, Biochim. Biophys. Acta 164:426 (1968).Google Scholar
  14. 14.
    H. Vonkeman and D.A. van Dorp, The action of prostaglandin synthetase on 2-arachidonoyl-lecithin, Biochim. Biophys. Acta 164:430 (1968).Google Scholar
  15. 15.
    W. Vogt, U. Meyer, H. Kunze, E. Lufft and S. Babilli, Entstehung von SRSC in der durchstromten Meerschweichenlunge durch phospholipase A. Identifizierung mit prostaglandin, NaunynSchmiedebergs Arch. Exp. Path. Pharmak. 262:124 (1969).Google Scholar
  16. 16.
    J. Bartels, H. Kunze, W. Vogt and G. Willis, Prostaglandin: liberation from and formation in perfused frog intestineNaunyn-Schmiedebergs Arch. Pharmacol. 266:207 (1970).Google Scholar
  17. 17.
    B. Haye, S. Champion and C. Jacquemin, Control of TSH of a phospholipase A2 activity, a limiting factor in the biosynthesis of prostaglandins in the thyroid, FEBS Lett. 30: 253 (1973).PubMedCrossRefGoogle Scholar
  18. 18.
    R.J. Flower and G.J. Blackwell, The importance of phospholipase A2 in prostaglandin biosynthesis, Biochem. Pharmacol. 25: 285 (1976).Google Scholar
  19. 19.
    P.C. Isakson, A. Raz, W. Hsueh and P. Needleman, Lipases and prostaglandin biosynthesis, in: “Advances in prostaglandin and thromboxane research”, C. Galli et al., ed., Raven Press, New York, p. 113 (1978).Google Scholar
  20. 20.
    T.K. Bills, J.B. Smith and N.J. Silver, Selective release of arachidonic acid from the phospholipids of human platelets in response to thrombin, J. Clin. Invest. 60:1 (1977).PubMedCrossRefGoogle Scholar
  21. 21.
    G.J. Blackwell, W.G. Duncombe, R.J. Flower, M.F. Parsons and J.R. Vane, The distribution and metabolism of arachidonic acid in rabbit platelets during aggregation and its modification by drugs, Br. J. Pharmacol. 59:353 (1977).PubMedGoogle Scholar
  22. 22.
    E.G. Lapetina, K.A. Chandrabose and P. Cuatrecasas, Ionophore A 23187- and thrombin-induced platelet aggregation: independence from cyclo-oxygenase products, Proc. Natl. Acad. Sci. USA 75:818 (1978).PubMedCrossRefGoogle Scholar
  23. 23.
    S.L. Hong and L. Levine, Inhibition of arachidonic acid release from cells as the biochemical action of anti-inflammatory cortico-steroids, Proc. Natl. Acad. Sci. USA 73:1730 (1976).PubMedCrossRefGoogle Scholar
  24. 24.
    H. van den Bosch, Intracellular phospholipases A, Biochim. Biophys. Acta 604:191 (1980).Google Scholar
  25. 25.
    P. Eisbach, J. Weiss, R.C. Franson, S. Beckerdite-Quagliata, A. Schneider and L. Harris, Separation and purification of a potent bactericidal/permeability increasing protein and a closely associated phospholipase A9 from rabbit polymorphonuclear leucocytes, J. Biol. Chem. 254:11000 (1979).Google Scholar
  26. 26.
    R.M. Kramer, C. Wüthrich, C. Bollier, P.R. Allegrini and P. Zahler, Isolation of phospholipase A2 from sheep erythrocyte membranes in the presence of detergents, Biochim. Biophys. Acta 507:381 (1978).Google Scholar
  27. 27.
    R. Kannagi and K. Koizumi, Effect of different physical states of phospholipid substrates on partially purified phospholipase A2 activity, Biochim. Biophys. Acta 556:423 (1979).Google Scholar
  28. 28.
    R.J. Apitz-Castro, M.A. Mas, M.R. Cruz and M.K. Jain, Isolation of homogeneous phospholipase A2 from human platelets, Biochem. Biophys. Res. Commun. 91:63 (1979).Google Scholar
  29. 29.
    Y. Natori, M. Nishijima, S. Nojima and H. Satoh, Purification and properties of a membrane-bound phospholipase A2 from rat ascites hepatoma 108A cells, J. Biochem. 87:959 (1980).PubMedGoogle Scholar
  30. 30.
    H. van den Bosch and A.J. Aarsman, A review on methods of phospholipase A determination, Agents and Actions 9:382 (1979).PubMedCrossRefGoogle Scholar
  31. 31.
    A.J. Aarsman, L.L.M. van Deenen and H. van den Bosch, Synthesis of acylthioester analogs of lysolecithin and their use in a continuous spectrophotometric assay for lysophospholipases, a method with potential applicability to other lipolytic enzymes, Bioorganic Chemistry 5:241 (1976).CrossRefGoogle Scholar
  32. 32.
    C.O. Rock and F. Snyder, Rapid purification of phospholipase A2 from Crotalus adamanteus venom by affinity chromatography, J. Biol. Chem. 250:6564 (1975).PubMedGoogle Scholar
  33. 33.
    R.E. Barden, P.L. Darke, R.A. Deems and E.A. Dennis, Interaction of phospholipase A2 from cobra venom with cibacron blue F3GA, Biochemistry 19:1621 (1980).PubMedCrossRefGoogle Scholar
  34. 34.
    R.J. Flower, Phospholipases and their relevance to prostaglandin biosynthesis, in: “The prostaglandin system”, F. Berti and G.P. Velo, eds., Plenum Press, New York, p. 27 (1981).Google Scholar
  35. 35.
    G.H. de Haas, N.M. Postema, W. Nieuwenhuizen and L.L.M. van Deenen, Purification and properties of an anionic zymogen of phospholipase A from porcine pancreas, Biochim. Biophys. Acta 159:118 (1969).Google Scholar
  36. 36.
    W.C. Pickett, R.L. Jesse and P. Cohen, Trypsin-induced phospholipase activity in human platelets, Biochem. J. 160:405 (1976).PubMedGoogle Scholar
  37. 37.
    S.L. Hong, R. Polsky-Cynkin and L. Levine, Stimulation of prostaglandin biosynthesis by vasoactive substances in methylcholanthrene-transformed mouse BALB/3T3 cells, J. Biol. Chem. 251:776 (1976).PubMedGoogle Scholar
  38. 38.
    M.B. Feinstein, E.L. Becher and C. Fraser, Thrombin, collagen and A 23187 stimulated endogenous platelet arachidonate metabolism: differential inhibition by PGE1, local anaesthetics and a serine-protease inhibitor, Prostaglandins 14: 1075 (1977).PubMedGoogle Scholar
  39. 39.
    R. Walenga, J.Y. Vanderhoek and M.B. Feinstein, Serine esterase inhibitors block stimulus-induced mobilization of arachidonic acid and phosphatidylinositol-specific phospholipase C activity in platelets, J. Biol. Chem. 255:6024 (1980).PubMedGoogle Scholar
  40. 40.
    R.J. Gryglewski, B. Panczenko, R. Korbut, L. Grodszinska and A. Ocetkiewicz, Cortico-steroids inhibit prostaglandin release from perfused lungs of sensitized guinea pigs, Prosta glandins 10:343 (1975).PubMedGoogle Scholar
  41. 41.
    R.J. Flower and G.J. Blackwell, Anti-inflammatory steroids induce the biosynthesis of a phospholipase A2 inhibitor which prevents prostaglandin generation, Nature 278:456 (1979).PubMedCrossRefGoogle Scholar
  42. 42.
    F. Hirata, E. Schiffmann, K. Venkatasubramanian, D. Salomon and J. Axelrod, A phospholipase A2 inhibitory protein in rabbit neutrophils induced by glucocorticoids, Proc. Natl. Acad. Sci. USA 77:2533 (1980).PubMedCrossRefGoogle Scholar
  43. 43.
    G.J. Blackwell, R. Carnuceio, M. DiRosa, R.J. Flower, L. Parente and P. Persico, Macrocortin: a polypeptide causing the anti-phospholipase effect of glucocorticoids, Nature 287:147 (1980).PubMedCrossRefGoogle Scholar
  44. 44.
    F.P. Nijkamp, R.J. Flower, S. Moncada and J.R. Vane, Partial purification of rabbit aorta contracting substance-releasing factor and inhibition of its activity by anti-inflammatory steroids, Nature 263:479 (1976).PubMedCrossRefGoogle Scholar
  45. 45.
    F. Hirata, B.A. Corcoran, K. Venkatasubramanian, E. Schiffmann and J. Axelrod, Chemoattractants stimulate degradation of methylated phospholipids and release of arachidonic acid in rabbit leucocytes, Proc. Natl. Acad. Sci. USA 76:2640 (1979).PubMedCrossRefGoogle Scholar
  46. 46.
    W.C. Pickett, R.L. Jesse and P. Cohen, Initiation of phospholipase A2 activity in human platelets by the calcium ion ionophore A 23187, Biochim. Biophys. Acta 486:209 (1977)Google Scholar
  47. 47.
    S. Rittenhouse-Simmons and D. Deykin, The activation by Cat+ of platelet phospholipase A2. Biochim. Biophys. Acta 543:409 (1978).Google Scholar
  48. 48.
    M. Minkes, N. Stanford, M.M.Y. Chi, G.J. Roth, A. Raz, P. Needleman and P.W. Majerus, Cyclic adenosine 3’,5’-monophosphate inhibits the availability of arachidonate to prostaglandin synthetase in human platelet suspensions, J. Clin. Invest. 59:449 (1977).PubMedCrossRefGoogle Scholar
  49. 49.
    E.G. Lapetina, C.J. Schmitges, K. Chandrabose and P. Cuatrecasas, Cyclic adenosine 3’,5’-monophosphate and prostacyclin inhibit membrane phospholipase activity in platelets, Biochem. Biophys. Res. Commun. 76:828 (1977).Google Scholar
  50. 50.
    E. Frei and P. Zahler, Phospholipase A22 from sheep erythrocyte membranes. Ca2+ dependence and lozalization, Biochim. Biophys. Acta 550:450 (1979).Google Scholar
  51. 51.
    S. Rittenhouse-Simmons, Production of diglyceride from phosphatidylinositol in activated human platelets, J. Clin. Invest. 63:580 (1979).PubMedCrossRefGoogle Scholar
  52. 52.
    R.L. Bell and P.W. Majerus, Thrombin-induced hydrolysis of phosphatidylinositol in human platelets, J. Biol. Chem. 255: 1790 (1980).PubMedGoogle Scholar
  53. 53.
    R.L. Bell, D.A. Kennerly, N. Stanford and P.W. Majerus, Diglyceride lipase: a pathway for arachidonate release from human platelets, Proc. Natl. Acad. Sci. USA 76:3238 (1979).PubMedCrossRefGoogle Scholar
  54. 54.
    M.J. Broekman, J.W. Ward and A.J. Marcus, Phospholipid metabolism in stimulated human platelets. Changes in phosphatidylinositol, phosphatidic acid and lysophospholipids, J. Clin. Invest. 66:275 (1980).PubMedCrossRefGoogle Scholar
  55. 55.
    M.L. McKean, J.B. Smith and M.J. Silver, Formation of lysophosphatidylcholine by human platelets in response to thrombin, J. Biol. Chem. 256:1522 (1981).PubMedGoogle Scholar
  56. 56.
    E.G. Lapetina, M.M. Billah and P. Cuatrecasas, The initial action of thrombin on platelets. Conversion of phosphatidylinositol to phosphatidic acid preceding the production of arachidonic acid, J. Biol. Chem. 256:5037 (1981).PubMedGoogle Scholar
  57. 57.
    M.M. Billah, E.G. Lapetina and P. Cuatracasas, Phospholipase A2 activity specific for phosphatidic acid. A possible mechanism for the production of arachidonic acid in platelets, J. Biol. Chem. 256:5399 (1981).PubMedGoogle Scholar
  58. 58.
    S.L. Hong and D. Deykin, The activation of phosphatidylinositol-hydrolyzing phospholipase A2 during prostaglandin synthesis in transformed mouse BALB/3T3 cells, J. Biol. Chem. 256:5215 (1987).Google Scholar

Copyright information

© Plenum Press, New York 1983

Authors and Affiliations

  • H. van den Bosch
    • 1
  1. 1.Biochemistry LaboratoryState University of UtrechtCH UtrechtThe Netherlands

Personalised recommendations