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Glutathione Transferases Catalyzing Leukotriene C Synthesis and Metabolism of Leukotrienes C4 and E4in Vivo and in Vitro

  • Sven Hammarström
  • Lars Örning
  • Kerstin Bernström
  • Bengt Gustafsson
  • Elisabeth Norin
  • Bengt Mannervik
  • Helgi Jensson
  • Per Ålin
Part of the GWUMC Department of Biochemistry Annual Spring Symposia book series (GWUN)

Abstract

Glutathione transferases constitute a group of enzymes that catalyze several reactions involving glutathione (Mannervik, 1985). Their main function, according to current concepts, is to detoxify and accelerate the excretion of certain xenobiotic compounds (Chasseaud, 1979) by catalyzing the conjugation of glutathione with these electro-philic substrates. In addition, glutathione transferases also catalyze other reactions (e. g., peroxidase and isomerase reactions). We have recently reported (Mannervik et al., 1984) that six basic glutathione transferases from rat liver cytosol (Mannervik and Jensson, 1982) catalyze the conversion of LTA4 or its methyl ester to LTC4. One of the enzymes was a considerably more efficient catalyst of the reaction than the remaining five.

Keywords

Chronic Granulomatous Disease Compound VIII Glutathione Transferase Raney Nickel Monomethyl Ester 
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.

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References

  1. Appelgren, L.E., and Hammarström, S., 1982, Distribution and metabolism of 3H-labeled leukotriene C3 in mice, J. Biol. Chem. 257:531–535.PubMedGoogle Scholar
  2. Bernström, K., and Hammarström, S., 1981, Metabolism of leukotriene D by porcine kidney, J. Biol. Chem. 256:9579–9582.PubMedGoogle Scholar
  3. Bernström, K., and Hammarström, S. 1985, Metabolism of leukotriene E4 by rat tissues, Arch. Biochem. Biophys. submitted.Google Scholar
  4. Chasseaud, L.F., 1979, The role of glutathione and glutathione-S-transferases in the metabolism of chemical carcinogens, Adv. Cancer Res. 29:175–274.PubMedCrossRefGoogle Scholar
  5. Clark, D.A., Goto, G., Marfat, A., Corey, E.J., Hammarström, S., and Samuelsson, B., 1980, 11-rraAw-Leukotriene C: A naturally occurring slow reacting substance, Biochem. Biophys. Res. Commun. 94:1133–1139.PubMedCrossRefGoogle Scholar
  6. Goetzl, E.J., 1982, The conversion of leukotriene C4 to isomers of leukotriene B4 by human eosinophil peroxidase, Biochem. Biophys. Res. Commun. 106:270–275.PubMedCrossRefGoogle Scholar
  7. Hammarström, S., 1981, Metabolism of leukotriene C3 in the guinea pig. Identification of metabolites formed by lung, liver and kidney, J. Biol. Chem. 256:9573–9578.PubMedGoogle Scholar
  8. Hammarström, S., Samuelsson, B., Clark, D.A., Goto, G., Marfat, A., Mioskowski, C, and Corey, E.J., 1979, Stereochemistry of leukotriene C-l, Biochem. Biophys. Res. Commun. 92:946–953.CrossRefGoogle Scholar
  9. Hammarström, S., Bernström, K., Örning, L., Dahlén, S. E., Hedqvist, P., Smedegård, G., and Revenäs, B., 1981, Rapid in vivo metabolism of leukotriene C3 in the monkey Macaca irus, Biochem. Biophys. Res. Commun. 101:1109–1115.CrossRefGoogle Scholar
  10. Hendersson, W.R., and Klebanoff, S.J., 1983, Leukotriene production and inactivation by normal, chronic granulomatous disease and myeloperoxidase deficient neutrophils, J. Biol. Chem. 258:13522–13527.Google Scholar
  11. Lee, C.W., Lewis, R.A., Tauber, A.L, Mehrotra, M., Corey, E.J., and Austen, K.F., 1983, The myeloperoxidase-dependent metabolism of leukotrienes C4, D4, and E4 to 6-trans-leukotriene B4 diastereoisomers and the subclass-specific 5-diastereoisomeric sulfoxides, J. Biol. Chem. 258:15004–15010.PubMedGoogle Scholar
  12. Mannervik, B., 1985, The isoenzymes of glutathione transferase, Adv. Enzymol. 57:357–417.PubMedGoogle Scholar
  13. Mannervik, B., and Jensson, H., 1982, Binary combinations of four protein subunits with different catalytic specificities explain the relationship between six basic glutathione-S-transferases in rat liver cytosol, J. Biol. Chem. 257:9909–9912.PubMedGoogle Scholar
  14. Mannervik, B., Jensson, H., Älin, P., Örning, L., and Hammarström, S., 1984, Transformation of leukotriene A4 methyl ester to leukotriene C4 monomethyl ester by cytosolic rat glutathione trans-ferases, FEBS Lett. 175:289–293.PubMedCrossRefGoogle Scholar
  15. Murphy, R.C, Hammarström, S., and Samuelsson, B., 1979, Leukotriene C: A slow reacting substance from murine mastocytoma cells, Proc. Natl. Acad. Sci. U.S.A. 76:4275–4279.PubMedCrossRefGoogle Scholar
  16. Örning, L., and Hammarström, S., 1980, Inhibition of leukotriene C and leukotriene D biosynthesis, J. Biol. Chem. 255:8023–8026..PubMedGoogle Scholar
  17. Örning, L., Norin, E., Gustafsson, B., and Hammarström, S., 1984, On the metabolism of leukotriene C4 in the rat: Identification of two fecal metabolites, J. Biol. Chem. 260:(in press).Google Scholar
  18. Söderström, M., Mannervik, B., Örning, L., and Hammerström, S., 1985, Leukotriene C4 formation catalyzed by three distinct forms of human cytosolic glutathione transferase, Biochem. Biophys. Res. Commun. 228:265–270.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1985

Authors and Affiliations

  • Sven Hammarström
    • 1
  • Lars Örning
    • 1
  • Kerstin Bernström
    • 1
  • Bengt Gustafsson
    • 2
  • Elisabeth Norin
    • 2
  • Bengt Mannervik
    • 3
  • Helgi Jensson
    • 3
  • Per Ålin
    • 3
  1. 1.Department of Physiological ChemistryKarolinska InstitutetStockholmSweden
  2. 2.Department of Germfree ResearchKarolinska InstitutetStockholmSweden
  3. 3.Department of Biochemistry, Arrhenius LaboratoryUniversity of StockholmStockholmSweden

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