Advertisement

Cytochrome P450 and the Metabolism of Arachidonic Acid and Oxygenated Eicosanoids

  • Jorge H. Capdevila
  • Darryl Zeldin
  • Keiko Makita
  • Armando Karara
  • John R. Falck
Chapter

Abstract

Eukaryotic cells contain substantial amounts of arachidonic acid (AA; 5,8,11,14-eicosatetraenoic acid) esterified predominantly to the sn-2 position of cellular glycerophospholipids. As with many lipid-derived mediators, e.g., cholesterol, phosphoinositides, diglycerides, AA serves a structural role, as a component of cellular membranes, and an important functional role, as a participant in a variety of receptor/agonist-mediated signaling cascades.1–4 In the absence of stimuli, the intracellular levels of nonesterified AA are nearly undetectable. However, most organ cells possess an elaborate enzymatic machinery that, in response to a variety of stimuli, catalyzes: (1) the hydrolytic cleavage of the AA molecule form selected, hormonally sensitive phospholipid pools, (2) the transduction of chemical information into the fatty acid molecular template by means of regio- and stereospecific oxygenation reactions, and (3) the decoding of that chemical information either by receptor-mediated processes or, alternatively, by the direct effects of these oxygenated metabolites on metabolic pathways1–4 (Fig. 1). As a net result, these processes provide cells with a rapid and versatile on/off molecular switch for the intra- or intercellular transduction and/or amplification of functionally meaningful information.

Keywords

Arachidonic Acid Allene Oxide Microsomal Cytochrome Epoxyeicosatrienoic Acid Kidney Microsome 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Needleman, P., Turk, J., Jakschik, B. A., Morrison, A. R., and Lefkowith, J. B., 1986, Arachidonic acid metabolism, Annu. Rev. Biochem. 55:62–102 and references therein.CrossRefGoogle Scholar
  2. 2.
    Smith, W. L., Marnett, L. J., and DeWitt, D. L., 1991, Prostaglandin and thromboxane biosynthesis, Pharmacol. Ther. 49: 153–179.PubMedCrossRefGoogle Scholar
  3. 3.
    Smith, W. L., 1992, Prostanoid biosynthesis and mechanism of action, Am. J. Physiol. 263: F181 - F191PubMedGoogle Scholar
  4. 4.
    Ford-Hutchinson, A. W., Gresser, M., and Young, R. N., 1994, 5-Lipoxygenase, Annu. Rev. Biochem. 63: 383–417.CrossRefGoogle Scholar
  5. 5.
    Fitzpatrick, F. A., and Murphy, R. C., 1989, Cytochrome P-450 metabolism of arachidonic acid: Formation and biological actions of “epoxygenase”-derived eicosanoids, Pharmacol. Rev. 40:229–241.Google Scholar
  6. 6.
    McGiff, J. C., 1991, Cytochrome P-450 metabolism of arachidonic acid, Annu. Rev. Pharmacol. Toxicol. 31: 339–369.PubMedCrossRefGoogle Scholar
  7. 7.
    Capdevila, J. H., Falck, J. R., and Estabrook, R. W., 1992, Cytochrome P-450 and the arachidonate cascade, FASEB J. 6: 731–736.PubMedGoogle Scholar
  8. 8.
    Oliw, E. H., 1994, Oxygenation of polyunsaturated fatty acids by cytochrome P450 monooxygenases, Prog. Lipid Res. 33: 329–354.PubMedCrossRefGoogle Scholar
  9. 9.
    Marnett, L. J., 1992, Aspirin and the potential role of prostaglandins in colon cancer, Cancer Res. 52: 5575–5589.PubMedGoogle Scholar
  10. 10.
    DiAgustine, R. P., and Fouts, J. R., 1969, The effects of unsaturated fatty acids on hepatic microsomal drug metabolism and cytochrome P-450, Biochem. J. 115: 547–554.Google Scholar
  11. 11.
    Pessayre, D., Mazel, P., Descatoire, V., Rogier, E., Feldmann, G., and Benhamou, J. P., 1979, Inhibition of hepatic drug-metabolizing enzymes by arachidonic acid, Xenobiotica 9: 301–310.PubMedCrossRefGoogle Scholar
  12. 12.
    Cinti, D. L., and Feinstein, M. B., 1976, Platelet cytochrome P-450: A possible role in arachidonateinduced aggregation, Biochem. Biophys. Res. Commun. 73: 171–179.PubMedCrossRefGoogle Scholar
  13. 13.
    Capdevila, J. H., Parkhill, L., Chacos, N., Okita, R., Masters, B. S., and Estabrook R. W., 1981, The oxidative metabolism of arachidonic acid by purified cytochromes P-450, Biochem. Biophys. Res. Commun. 101: 1357–1363.PubMedCrossRefGoogle Scholar
  14. 14.
    Capdevila, J. H., Chacos, N. Werringloer, J., Prough, R. A., and Estabrook, R. W., 1981, Liver microsomal cytochrome P-450 and the oxidative metabolism of arachidonic acid, Proc. Natl. Acad. Sci. USA 78: 5362–5366.Google Scholar
  15. 15.
    Oliw, E. H., and Oates, J. A., 1981, Oxygenation of arachidonic acid by hepatic microsomes of the rabbit. Mechanism of biosynthesis of two vicinal diols, Biochim. Biophys. Acta 666: 327–340.PubMedCrossRefGoogle Scholar
  16. 16.
    Morrison, A. R., and Pascoe, N., 1981, Metabolism of arachidonic acid through NADPH-dependent oxygenase of renal cortex, Proc. Natl. Acad. Sci. USA 78: 7375–7378.PubMedCrossRefGoogle Scholar
  17. 17.
    Capdevila, J., Marnett, L. J., Chacos, N., Prough, R. A., and Estabrook, R. W. 1982, Cytochrome P-450-dependent oxygenation of arachidonic acid to hydroxyeicosatetraenoic acids, Proc. Natl. Acad. Sci. USA 79: 767–770.PubMedCrossRefGoogle Scholar
  18. 18.
    Chacos, N., Falck, J. R., Wixtrom, C., and Capdevila, J, 1982, Novel epoxides formed during the liver cytochrome P-450 oxidation of arachidonic acid, Biochem. Biophys. Res. Commun. 104: 916–922.PubMedCrossRefGoogle Scholar
  19. 19.
    Oliw, E. H., Guengerich, E. P., and Oates J. A., 1982, Oxygenation of arachidonic acid by hepatic monooxygenases, J. Biol. Chem. 257: 3771–3781.PubMedGoogle Scholar
  20. 20.
    Capdevila, J. H., Chacos, N., Falck, J. R., Manna, S., Negro-Vilar, A., and Ojeda, S. R., 1983, Novel hypothalamic arachidonate products stimulate somatostatin release from the median eminence, Endocrinology 113: 421–423.PubMedCrossRefGoogle Scholar
  21. 21.
    Jacobson, H. R., Corona, S., Capdevila, J. H., Chacos, N., Manna, S., Womack, A., and Falk, J. R., 1984, in: Prostaglandins and Membrane Ion Transport (P. Braquet, J. C. Frolich, S. Nicosia, and R. Garay, eds.), Raven Press, New York.Google Scholar
  22. 22.
    Capdevila, J. H., Pramanik, B., Napoli, J. L., Manna, S., and Falck, J. R., 1984, Arachidonic acid epoxidation: Epoxyeicosatrienoic acids are endogenous constituents of rat liver, Arch. Biochem. Biophys. 231: 511–517.PubMedCrossRefGoogle Scholar
  23. 23.
    Rahimtula, A. D., and O’Brien, P. J., 1974, Hydroperoxide catalyzed liver microsomal aromatic hydroxylation reactions involving cytochrome P-450, Biochem. Biophys. Res. Commun. 60: 440–447.PubMedCrossRefGoogle Scholar
  24. 24.
    Weiss, R. H., Arnold, J. L., and Estabrook, R. W., 1987, Transformation of an arachidonic acid hydroperoxide into epoxyhydroxy and trihydroxy fatty acids by liver microsomal cytochrome P-450, Arch. Biochem. Biophys. 252: 334–338.PubMedCrossRefGoogle Scholar
  25. 25.
    Ullrich, V., Castle, L., and Haurand, M., 1982, Cytochrome P-450 as an oxene transferase, in: Oxygenases and Oxygen Metabolism ( M. Nozaki, S. Yamamoto, Y. Ishimura, M. J. Coon, L. Ernster, and R. W. Estabrook, eds.), Academic Press, New York.Google Scholar
  26. 26.
    Hecker, M., and Ullrich, V., 1989, On the mechanism of prostacyclin and thromboxane Az biosynthesis, J. Biol. Chem. 264: 141–150.PubMedGoogle Scholar
  27. 27.
    White, R. E., and Coon, M. G., 1980, Oxygen activation by cytochrome P-450, Annu. Rev. Biochem. 49: 315–356.PubMedCrossRefGoogle Scholar
  28. 28.
    Hamilton, G. A., 1964, Oxidation by molecular oxygen. II. The oxygen atom transfer mechanism for mixed-function oxidases and the model mixed-function oxidases, J. Am. Chem. Soc. 86: 3391–3396.CrossRefGoogle Scholar
  29. 29.
    Yokoyama, C., Miyata, A., Ihara, H., Ullrich, V., and Tanabe, T., 1991, Molecular cloning of human platelet thromboxane A synthase, Biochem. Biophys. Res. Commun. 178: 1479–1484.PubMedCrossRefGoogle Scholar
  30. 30.
    Ohashi, K., Ruan, K. H., Kulmacz, R. J., Wu, K. K., and Wang, L. H., 1992, Primary structure of human thromboxane synthase determined from the cDNA sequence, J. Biol. Chem. 267: 789–793.PubMedGoogle Scholar
  31. 31.
    Hara, S., Miyata, A., Yokoyama, C., Inoue, H., Burgger, R., Lottspeich, F., Ullrich, V., and Tanabe, T., 1994, Isolation and molecular cloning of prostacyclin synthase from bovine endothelial cells, J. Biol. Chem. 269: 19897–19903.PubMedGoogle Scholar
  32. 32.
    Song, W. C., Funk, C. D., and Brash, A. R., 1993, Molecular cloning of an allene oxide synthase: A cytochrome P450 specialized for the metabolism of fatty acid hydroperoxides, Proc. Natl. Acad. Sci. USA 90: 8519–8523.PubMedCrossRefGoogle Scholar
  33. 33.
    Wong, P. Y. K., Malik, K. U., Taylor, B. M., Schneider, W. P., McGiff, J. C., and Sun, F. F., 1985, Epoxidation of prostacyclin in the rabbit kidney, J. Biol. Chem. 260: 9150–9153.PubMedGoogle Scholar
  34. 34.
    Oliw, E. H., 1984, Metabolism of 5(6)-epoxyeicosatrienoic acid by ram seminal vesicles formation of novel prostaglandin Ei metabolites, Biochim. Biophys. Acta 793: 408–415.PubMedCrossRefGoogle Scholar
  35. 35.
    Zhang, J. Y., Prakash, C., Yamashita, K., and Blair, I. A., 1992, Regiospecific and enantioselective metabolism of 8,9-epoxyeicosatrienoic acids by cyclooxygenase, Biochem. Biophys. Res. Commun. 183: 138–143.PubMedCrossRefGoogle Scholar
  36. 36.
    Jajjo, H. K., Capdevila, J. H., Falck, J. R., Bhatt, R. K., and Blair, I. A., 1992, Metabolism of 12(R)-hydroxyeicosatetraenoic acid by rat liver microsomes, Biochim. Biophys. Acta 1123: 110–116.CrossRefGoogle Scholar
  37. 37.
    Capdevila, J., Mosset, P., Yadagiri, P., Sun Lumin, and Falck, J. R., 1988, NADPH-dependent microsomal metabolism of 14,15-epoxyeicosatrienoic acid to diepoxides and epoxyalcohols, Arch. Biochem. Biophys. 261: 122–132.PubMedCrossRefGoogle Scholar
  38. 38.
    Hamberg, M., and Samuelsson, B., 1966, Prostaglandins in human seminal plasma. Prostaglandins and related factors, J. Biol. Chem. 241: 257–263.PubMedGoogle Scholar
  39. 39.
    Oliw, E. H., 1989, Biosynthesis of 18(R)-hydroxyeicosatetraenoic acid from arachidonic acid by microsomes of monkey seminal vesicles, J. Biol. Chem. 264: 17845–17853.PubMedGoogle Scholar
  40. 40.
    Israelson, U., Hamberg, M., and Samuelsson, B., 1969, Biosynthesis of 19-hydroxy-prostaglandin Ai, Rut: J. Biochem. 11: 390–394.Google Scholar
  41. 41.
    Kupfer, D., 1982, Endogenous substrates of monooxygenases: Fatty acids and prostaglandins, in: Hepatic Cytochrome P-450 Monooxygenase System, (J. B. Schenkman and D. Kupfer, eds.), Pergamon Press, Elmsford, NY, pp. 157–182.Google Scholar
  42. 42.
    Nelson, D. R., Kamataki, T., Waxman, D. J., Guengerich, F. P., Estabrook, R. W., Feyereisen, R., Gonzalez, E J., Coon, M. J., Gunsalus, I. C., Gotoh, O., Okuda, K., and Nebert, D. W., 1993, The P450 superfamily: Update on new sequences, gene mapping, accession numbers, early trivial names of enzymes and nomenclature, DNA Cell Biol. 12: 1–51.PubMedCrossRefGoogle Scholar
  43. 43.
    Hardwick, J. P., Song, B. J., Huberman, E., and Gonzalez, E J., 1987, Isolation, complementary DNA sequence, and regulation of rat hepatic lauric acid to-hydroxylase (cytochrome P450t.A(0), J. Biol. Chem. 262: 801–810.PubMedGoogle Scholar
  44. 44.
    Sharma, R. K., Doig, M. V., Lewis, D. F. V., and Gibson, G., 1989, Role of hepatic and renal cytochrome P450 IVA1 in the metabolism of lipid substrates, Biochem. Pharmacol. 38: 3621–3629.PubMedCrossRefGoogle Scholar
  45. 45.
    Imaoka, S., Tanaka, S., and Funae, Y., 1989, co and (co-1)-hydroxylation of lauric acid and arachidonic acid by rat renal cytochrome P-450, Biochem. Int. 18: 731–740.Google Scholar
  46. 46.
    Imaoka, S., Nagashima, K., and Funae, Y., 1990, Characterization of three cytochrome P450s purified from renal microsomes of untreated male rats and comparison with human renal cytochrome P450, Arch. Biochem. Biophys. 276: 473–480.PubMedCrossRefGoogle Scholar
  47. 47.
    Kimura, S., Hanioka, N., Matsunaga, E., and Gonzalez, F. J., 1989, The rat clofibrate-inducible CYP4A gene subfamily I. Complete intron and exon sequence of the CYP4A1 and CYP4A2 genes, unique exon organization and identification of a conserved 19-bp upstream element, DNA 8: 503–516.Google Scholar
  48. 48.
    Kimura, S., Hardwick, J. R, Kozac, C. A., and Gonzalez, F J., 1989, The rat clofibrate inducible CYP4A subfamily II. cDNA sequence of IVA3, mapping of the Cyp4a locus to mouse chromosome 4, and coordinated and tissue specific regulation of the CYP4A genes, DNA 8: 517–525.Google Scholar
  49. 49.
    Stromsteadt, M., Hayashi, S., Zaphiropoulos, R. G., and Gustafsson, J.A., 1990, Cloning and characterization of a novel member of the cytochrome P450 subfamily IVA in rat prostate, DNA Cell Biol. 8: 569–577.CrossRefGoogle Scholar
  50. 50.
    Matsubara, S., Yamamoto, S., Sogawa, K., Yokotani, N., Fujii-Kuriyama, Y., Haniu, M., Shively, J. E., Gotoh, O., Kusunose E., and Kusunose, M., 1987, cDNA cloning and inducible expression during pregnancy of the mRNA for rabbit pulmonary prostaglandin co-hydroxylase (cytochrome P-4501–2), J. Biol. Chem. 262: 13366–13371.Google Scholar
  51. 51.
    Johnson, E. F., Walker, D. L., Griffin, K. J., Clark, J. E., Okita, R. T., Muerhoff, S., and Masters, B. S., 1990, Cloning and expression of three rabbit kidney cDNAs encoding lauric acid u)-hydroxylases, Biochemistry 29: 873–879.PubMedCrossRefGoogle Scholar
  52. 52.
    Roman, L. J., Palmer, C.N.A., Clark, J. E., Muerhoff, S. A., Griffin, K. L., Johnson, E. F., and Masters, B. S. S., 1993, Expression of rabbit cytochrome P450A which catalyzes the to-hydroxylation of arachidonic acid, fatty acids, and prostaglandins, Arch. Biochem. Biophys. 307: 57–65.PubMedCrossRefGoogle Scholar
  53. 53.
    Yokotani, N., Kusunose, E., Sogawa, K., Kawashima, H., Kinosaki, M., Kusunose, M., and FujiiKuriyama, Y.,1991, cDNA cloning and expression of the mRNA for cytochrome P-450xd which shows a fatty acid w-hydroxylating activity. Eur. J. Biochem. 196: 531–536.Google Scholar
  54. 54.
    Yokotani, N., Bernhardt, R., Sogawa, K., Kusunose, E., Gotoh, O., Kusunose, M., and Fujii-Kuriyama, Y., 1989, Two forms of w-hydroxylase toward prostaglandin A and laurate. cDNA cloning and their expression, J. Biol. Chem. 264: 21665–21669.PubMedGoogle Scholar
  55. 55.
    Sawamura, A., Kusunose, E., Satouchi, K., and Kusunose, M., 1993, Catalytic properties of rabbit kidney fatty acid w-hydroxylase cytochrome P-450ka2 (CYP4A7), Biochim. Biophys. Acta 1168: 3036.Google Scholar
  56. 56.
    Kawashima, H., Kusunose, E., Kubota, I., Maekawa, M., and Kusunose, M., 1992, Purification and NH2-terminal amino acid sequences of human and rat kidney fatty acid co-hydroxylases, Biochim. Biophys. Acta 1123: 156–162.PubMedCrossRefGoogle Scholar
  57. 57.
    Palmer, C. N. A., Richardson, T. H., Griffin, K. J., Hsu, M., Muerhoff, A. S., Clark, J. E., and Johnson, E. F., 1993, Characterization of a cDNA encoding a human kidney cytochrome P-450 4A fatty acid w-hydroxylase and the cognate enzyme expressed in Escherichia coli, Biochim. Biophys. Acta 1172: 161–166.PubMedCrossRefGoogle Scholar
  58. 58.
    Imaoka, S., Ogawa, H., Kimura, S., and Gonzalez, F. J., 1993, Complete cDNA sequence and cDNA-directed expression of CYP4A11, a fatty acid omega-hydroxylase expressed in human kidney, DNA Cell Biol. 12: 893–899.PubMedGoogle Scholar
  59. 59.
    Jubiz, W., Radmark, O., Malmsten, C., Hansson, G., Lindgren, J. A., Palmblad, J., Uden, A. M., and Samuelsson, B., 1981, A novel leukotriene produced by stimulation of leukocytes with formylmethionylleucylphenylalanine, J. Biol. Chem. 257: 6106–6110.Google Scholar
  60. 60.
    Powell, W. S., 1984, Properties of leukotriene B4 20-hydroxylase from polymorphonuclear leukocytes, J. Biol. Chem. 259: 3082–3089.PubMedGoogle Scholar
  61. 61.
    Shak, S., and Goldstein, I. M., 1984, to-Oxidation is the major pathway for the catabolism of leukotriene B4 in human polymorphonuclear leukocytes, J. Biol. Chem. 259: 10181–10187.Google Scholar
  62. 62.
    Romano, M. C., Eckardt, R. D., Bender, P. E., Leonard, T. B., Straub, K. M., and Newton, J. F., 1987, Biochemical characterization of hepatic microsomal leukotriene B4 hydroxylases, J. Biol. Chem. 262: 1590–1595.PubMedGoogle Scholar
  63. 63.
    Kikuta, Y., Kusunose, E., Endo, K., Yamamoto, S., Sogawa, K., Fujii-Kuriyama, Y., and Kusunose, M., 1993, A novel form of cytochrome P-450 family 4 in human polymorphonuclear leukocytes, J. Biol. Chem. 268: 9376–9380.PubMedGoogle Scholar
  64. 64.
    Soberman, R. J., Okita, R. T., Fitzsimmons, B., Rokach, J., Spur, B., and Austen, K. F., 1987, Stereochemical requirements for substrate specificity of LTB4 20-hydroxylase, J. Biol. Chem. 262: 12421–12427.PubMedGoogle Scholar
  65. 65.
    Sumimoto, J., Takeshige, K., and Minakami, S., 1988, Characterization of human neutrophil leukotriene B4 omega-hydroxylase, a system involving a unique cytochrome P-450 and NADPH-cytochrome P-450 reductase, Eur. J. Biochem. 172: 315–324.PubMedCrossRefGoogle Scholar
  66. 66.
    Wong, P. Y. K., Westlund, P., Ramberg, M., Granstrom, E., Chao, P. W. H., and Samuelsson, B., 1984, w-Hydroxylation of 12-L-hydroxy-5,8,10,14-ei cos atetraenoic acid in human polymorphonuclear leukocytes, J. Biol. Chem. 259: 2683–2686.Google Scholar
  67. 67.
    Marcus, A. J., Safier, L. B., Ullman, H. L., Broekman, M. J., Islam, N., Oglesby, T. D., and Gorman, R., 1984, 12S,20-Dihydroxyeicosatetraenoic acid: A new eicosanoid synthesized by neutrophils from 12S-hydroxyeicosatetraenoic acid produced by thrombin-or collagen-stimulated platelets, Proc. Natl. Acad. Sci. USA 81: 903–907.Google Scholar
  68. 68.
    Flaherty, J. T., and Nishihira, J., 1987, 5-Hydroxyeicosatetraenoate promotes Cat+ and protein kinase C mobilization in neutrophils, Biochem. Biophys. Res. Commun. 148: 575–581.Google Scholar
  69. 69.
    Okita, R. T., Soberman, R. J., Bergholte, J. M., Masters, B. S. S., Hayes, R., and Murphy, R. C., 1987, co-Hydroxylation of 15-hydroxyeicosatetraenoic acid by lung microsomes from pregnant rabbits, Mol. Pharmacol. 32: 706–709.Google Scholar
  70. 70.
    Boucher, J. L, Delaforge, M., and Mansuy, D., 1991, Metabolism of lipoxins A4 and B4 and of their all-trans isomers by human leukocytes and rat liver microsomes, Biochem. Biophys. Res. Commun. 177: 134–139.PubMedCrossRefGoogle Scholar
  71. 71.
    Mizukami, Y., Sumimoto, H, and Minakami, S., 1993, Omega hydroxylation of lipoxin B4 by human neutrophil microsomes: Identification of omega-hydroxy metabolite of lipoxin B4 and catalysis by leukotriene B4 omega-hydroxylase (cytochrome P-450LTB omega), Biochim. Biophys. Acta 1168: 87–93.PubMedCrossRefGoogle Scholar
  72. 72.
    Samuelsson, B., Dahlen, S. E., Lindgren, J. A., Rouzer, C. A., and Serhan, C. H., 1987, Leukotrienes and lipoxins: Structures, biosynthesis and biological effects, Science 237: 1171–1176.PubMedCrossRefGoogle Scholar
  73. 73.
    Capdevila, J. H., Yadagiri, P., Manna, S., and Falck, J. R., 1986, Absolute configuration of the hydroxyeicosatetraenoic acids (HETEs) formed during catalytic oxygenation of arachidonic acid by microsomal cytochrome P-450, Biochem. Biophys. Res. Commun. 141: 1007–1011.PubMedCrossRefGoogle Scholar
  74. 74.
    Schwartzman, M. L., Balazy, M., Masferrer, J., Abraham, N. G., McGiff, J. C., and Murphy R. C., 1987, 12(R)-Hydroxyeicosatetraenoic acid: A cytochrome P450-dependent arachidonate metabolite that inhibits Na+,K+-ATPase in the cornea, Proc. Natl. Acad. Sci. USA 84: 8125–8129.Google Scholar
  75. 75.
    Oliw, E. H., 1993, Biosynthesis of 12(S)-hydroxyeicosatetraenoic acid by bovine corneal epithelium, Acta Physiol. Scand. 147: 117–121.PubMedCrossRefGoogle Scholar
  76. 76.
    Woollard, P. M., 1986, Stereochemical differences between 12-hydroxy-5,8,10,14-eicosatetraenoic acid in platelets and psoriatic lesions, Biochem. Biophys. Res. Commun. 141: 1007–1011.CrossRefGoogle Scholar
  77. 77.
    Murphy, R. C., Falck, J. R., Lumin, S., Yadagiri, P., Zirrolli, J. A., Balazy, M., Masferrer, J., Abraham, N. G., and Schwartzman, M. L., 1988, 12(R)-Hydroxyeicosatrienoic acid: A vasodilator cytochrome P-450-dependent arachidonate metabolite from bovine corneal epithelium, J. Biol. Chem. 263: 17197–17202.Google Scholar
  78. 78.
    Oliw, E. H., 1993, bis-Allylic hydroxylation of linoleic acid and arachidonic acid by human hepatic monooxygenases, Biochim. Biophys. Acta 1166: 258–263.Google Scholar
  79. 79.
    Lu, A. Y. H., Junk, K., and Coon, M. J., 1969, Resolution of the cytochrome P-450-containing cu-hydroxylation system of liver microsomes into three components, J. Biol. Chem. 244: 3714–3721.PubMedGoogle Scholar
  80. 80.
    Falck, J. R., Lumin, S., Blair, I., Dishman, E., Martin, M. V., Waxman, D. J., Guengerich, F. R, and Capdevila, J. H., 1990, Cytochrome P-450-dependent oxidation of arachidonic acid to 16-, 17-, and 18-hydroxyeicosatetraenoic acids, J. Biol. Chem. 265: 10244–10249.PubMedGoogle Scholar
  81. 81.
    Gonzalez, F. J., 1989, The molecular biology of cytochromes P450s, Pharmacol. Rev. 40: 243–288.Google Scholar
  82. 82.
    Rifkind, A. B., Kanetoshi, A., Orlinick, J., Capdevila, J. H., and Lee, C., 1994, Purification and biochemical characterization of two major cytochrome P-450 isoforms induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin in chick embryo liver, J. Biol. Chem. 269: 3387–3396.PubMedGoogle Scholar
  83. 83.
    Laethem, R. M., Balazy, M., Falck, J. R., Laethem, C. L., and Koop, D. R., 1993, Formation of 19(S)-, 19(R)-, and 18(R)-hydroxyeicosatetraenoic acids by alcohol-inducible cytochrome P450 2E1, J. Biol. Chem. 268: 12912–12918.PubMedGoogle Scholar
  84. 84.
    Lapuerta, L., Chacos, N., Falck, J. R., Jacobson, H., and Capdevila, J. H., 1988, Renal microsomal cytochrome P-450 and the oxidative metabolism of arachidonic acid, Am. J. Med. Sci. 31: 275–279.CrossRefGoogle Scholar
  85. 85.
    Iwai, N., and Inagami, T., 1990, Isolation of preferentially expressed genes in the kidneys of hypertensive rats, Hypertension 17: 161–169.CrossRefGoogle Scholar
  86. 86.
    Gebremedhin, D., Ma, Y. H., Imig, J. D., Harder, D. R., and Roman, R. J., 1993, Role of cytochrome P-450 in elevating renal vascular tone in spontaneously hypertensive rats, J. Vasc. Res. 30: 53–60.PubMedGoogle Scholar
  87. 87.
    Escalante, B., Sessa, W. C., Falck, J. R., Yadagin, P., and Schwartzman, M. L., 1990, Cytochrome P450-dependent arachidonic acid metabolites, 19- and 20-hydroxyeicosatetraenoic acids, enhance sodium-potassium ATPase activity in vascular smooth muscle, J. Cardiovasc. Pharmacol. 16: 438–443.PubMedCrossRefGoogle Scholar
  88. 88.
    Schwartzman, M. L., Falck, J. R., Yadagiri, P., and Escalante, B., 1989, Metabolism of 20-hydroxyeicosatetraenoic acid by cyclooxygenase. Formation and identification of novel endothelium-dependent vasoconstrictor metabolites, J. Biol. Chem. 264: 11658–11662.PubMedGoogle Scholar
  89. 89.
    Schwartzman, M. L., Ornata, K., Lin, F., Bhatt, R. K., Falck, J. R., and Abraham, N. G., 1991, Detection of 20-hydroxyeicosatetraenoic acid in rat urine, Biochem. Biophys. Res. Commun. 180: 445–449.PubMedCrossRefGoogle Scholar
  90. 90.
    Prakash, C., Zhang, J. Y., Falck, J. R., Chauhan, K., and Blair, I. A., 1992, 20-Hydroxyeicosatetraenoic acid is excreted as a glucuronide conjugate in human urine, Biochem. Biophys. Res. Commun. 185: 728–733.Google Scholar
  91. 91.
    Capdevila, J. H., Kim, Y. R., Martin-Wixtrom, C., Falck, J. R., Manna, S., and Estabrook, R. W., 1985, Influence of a fibric acid type of hypolipidemic agent on the oxidative metabolism of arachidonic acid by liver microsomal cytochrome P-450, Arch. Biochem. Biophys. 243: 8–19.PubMedCrossRefGoogle Scholar
  92. 92.
    Capdevila, J. H., Karara, A., Waxman, D. J., Martin, M. V., Falck, J. R., and Guengerich, F. P., 1990, Cytochrome P-450 enzyme-specific control of the regio-and enantiofacial selectivity of the microsomal arachidonic acid epoxygenase, J. Biol. Chem. 265: 10865–10871.PubMedGoogle Scholar
  93. 93.
    Capdevila, J. H., Wei, S., Yan, Y., Karara, A., Jacobson, H. R., Falck, J. R., Guengerich F. P., and DuBois, R. N., 1992, Cytochrome P-450 arachidonic acid epoxygenase. Regulatory control of the renal epoxygenase by dietary salt loading, J. Biol. Chem. 267: 21720–21726.PubMedGoogle Scholar
  94. 94.
    Karara, A., MaKita, K., Jacobson, J. R., Falck, J. R., Guengerich, F. P., DuBois, R. N., and Capdevila, J. H., 1993, Molecular cloning, expression, and enzymatic characterization of the rat kidney cytochrome P-450 arachidonic acid epoxygenase, J. Biol. Chem. 268: 13565–13570.PubMedGoogle Scholar
  95. 95.
    Daikh, B. E., Laethem, R. M., and Koop, D., 1994, Stereoselective epoxidation of arachidonic acid by cytochrome P-450s 2CAA and 2C2, J. Pharmacol. Exp. Ther. 269: 1130–1135.PubMedGoogle Scholar
  96. 96.
    Capdevila, J. H., Jacobson, H., and Zeldin, D., 1994, Molecular cloning, expression and enzymatic characterization of a human kidney cytochrome P450 arachidonic acid epoxygenase, J. Am. Soc. Nephrol. 5: 677.Google Scholar
  97. 97.
    Lund, J., Zaphiropoulos, P. G., Mode, A., Warner, M., and Gustafsson, J. A., 1991, Hormonal regulation of cytochrome P450 gene expression, Adv. Pharmacol. 22: 325–354.PubMedCrossRefGoogle Scholar
  98. 98.
    Lindberg, R. L., and Negishi, M., 1989, Alterations of mouse cytochrome P450coh substrate specificity by mutation of a single amino-acid residue, Nature 339: 632–634.PubMedCrossRefGoogle Scholar
  99. 99.
    Johnson, E. F, Kronbach, T. K., and Hsu, M. H., 1992, Analysis of the catalytic specificity of cytochrome P450 enzymes through site-directed mutagenesis, FASEB J. 6:700–705, and references therein.Google Scholar
  100. 100.
    Karara, A., Dishman, E., Blair, I., Falck, J. R., and Capdevila, J. H., 1989, Endogenous epoxyeicosatrienoic acids. Cytochrome P-450 controlled stereoselectivity of the hepatic arachidonic acid epoxygenase, J. Biol. Chem. 264: 19822–19827.PubMedGoogle Scholar
  101. 101.
    Karara, A., Dishman, E., Falck, J. R., and Capdevila, J. H., 1991, Endogenous epoxyeicosatrienoylphospholipids. Anovel class of cellular glycerolipids containing epoxidized arachidonate moieties, J. Biol. Chem. 266: 7561–7569.PubMedGoogle Scholar
  102. 102.
    Brezinski, M., and Serhan, C. N., 1990, Selective incorporation of 15(S)-hydroxyeicosatetraenoic acid in phosphatidylinositol of human neutrophile: Agonist-induced deacylation and transformation of stored hydroxyeicosanoids, Proc. Natl. Acad. Sci. USA 87: 6248–6252.PubMedCrossRefGoogle Scholar
  103. 103.
    Legrand, A. B., Lawson, J. A., Meyrick, B. O., Blair, I. A., and Oates, J. A., 1991, Substitution of 15-hydroxyeicosatetraenoic acid in the phosphoinositide signaling pathway, J. Biol. Chem. 266: 7570–7577.PubMedGoogle Scholar
  104. 104.
    Bertstrom, K., Kayganich, K., Murphy, R. C., and Fitzpatrick, F. A., 1992, Incorporation and distribution of epoxyeicosatrienoic acids into cellular phospholipids, J. Biol. Chem. 267: 3686–3690.Google Scholar
  105. 105.
    Karara, A., Wei, S., Spady, D., Swift, L., Capdevila, J. H., and Falck, J. R., 1992, Arachidonic acid epoxygenase: Structural characterization and quantification of epoxyeicosatrienoates in plasma, Biochem. Biophys. Res. Commun. 182: 1320–1325.PubMedCrossRefGoogle Scholar
  106. 106.
    Carrol, M. A., Garcia, M. P., Falck, J. R., and McGiff, J. C., 1990, 5,6-Epoxyeicosatrienoic acid, a novel arachidonate metabolite. Mechanism of vasoactivity in the rat, Circ. Res. 67: 1082–1088.Google Scholar
  107. 107.
    Frei, B., Winterhalter, K. H., and Richter, C., 1985, Quantitative and mechanistic aspects of the hydroperoxide-induced release of Ca`2 from rat liver mitochondria, Eur. J. Biochem. 149: 633–639.PubMedCrossRefGoogle Scholar
  108. 108.
    Sevanian, A., and Hochstein, R, 1985, Mechanisms and consequences of lipid peroxidation in biological systems, Annu. Rev. Nutr. 5:365–390, and references therein.Google Scholar
  109. 109.
    Gast, K., Zirwer, D., Ladhoff, M., Schreiber, J., Koelsch, R., and Kretschmer, K., 1982, Auto-oxidation-induced fusion of lipid vesicle, Biochim. Biophys. Acta 686: 99–109.PubMedCrossRefGoogle Scholar
  110. 110.
    Hauser, H., and Poupart, G., 1992, Lipid structure, in: The Structure of Biological Membranes ( R Yeagle, ed.), CRC Press, Ann Arbor, MI., pp. 3–71.Google Scholar
  111. 111.
    Yeagle, R, 1992, The dynamics of membrane lipids, in: The Structure of Biological Membranes ( P. Yeagle, ed.), CRC Press, Ann Arbor, MI, pp. 157–174.Google Scholar
  112. 112.
    Capdevila, J. H., Jin, Y., Karara, A., and Falck, J. R., 1993, Cytochrome P450 epoxygenase dependent formation of novel endogenous epoxyeicosatrienoyl-phospholipids, in: Eicosanoids and Other Bioactive Lipids in Cancer, Inflammation and Radiation Injury ( S. Nigam, L. J. Marnett, K. V. Honn, and T. L. Walden, Jr., eds.), Kluwer Academic, Boston, pp. 11–15.CrossRefGoogle Scholar
  113. 113.
    Karara, A., Dishman, E., Jacobson, H., Falck, J. R., and Capdevila, J. H., 1990, Arachidonic acid epoxygenase. Stereochemical analysis of the endogenous epoxyeicosatrienoic acids of human kidney cortex, FEBS Lett. 268: 227–230.PubMedCrossRefGoogle Scholar
  114. 114.
    Catella, F., Lawson, J. A., Fitzgerald, D. J., and Fitzgerald, G. A., 1990, Endogenous biosynthesis of arachidonic acid epoxides in humans: Increased formation in pregnancy-induced hypertension, Proc. Natl. Acad Sci. USA 87: 5893–5897.PubMedCrossRefGoogle Scholar
  115. 115.
    Makita, K., Takahashi, K., Karara, A., Jacobson, H. R., Falck, J. R., and Capdevila, J. H., 1994, Experimental and/or genetically controlled alterations of the renal microsomal cytochrome P450 epoxygenase induce hypertension in rats fed a high salt diet, J. Clin. Invest. 94: 2414–2420.PubMedCrossRefGoogle Scholar
  116. 116.
    Rapp, J. R, 1982, Dahl salt-susceptible and Dahl salt-resistant rats. A review, Hypertension 4: 753–763.PubMedCrossRefGoogle Scholar
  117. 117.
    Manuscript in preparation.Google Scholar

Copyright information

© Springer Science+Business Media New York 1995

Authors and Affiliations

  • Jorge H. Capdevila
    • 1
  • Darryl Zeldin
    • 2
  • Keiko Makita
    • 2
  • Armando Karara
    • 2
  • John R. Falck
    • 3
  1. 1.Departments of Medicine and BiochemistryVanderbilt University Medical SchoolNashvilleUSA
  2. 2.Department of MedicineVanderbilt University Medical SchoolNashvilleUSA
  3. 3.Department of Molecular GeneticsSouthwestern Medical CenterDallasUSA

Personalised recommendations