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Effects of microsomes and liposomes on glutathione transferase catalysed conjugation of benzo[a]pyrene diol epoxide with glutathione

Chemico-Biological Interactions
Publication Date
DOI: 10.1016/0009-2797(94)90003-5
  • Benzo[A]Pyrene Diol Epoxide
  • Glutathione Conjugation
  • Liposomes
  • Biology


Abstract trans-7,8-Dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[ a]pyrene [+)- anti-BPDE] is rapidly inactivated in aqueous solvents due to hydrolysis to tetraols. No significant effect on the rate of hydrolysis is observed in the presence of glutathione (GSH)-depleted cytosol. However, when the cytosolic fraction is replaced by a mixture of glutathione (GST)-isoenzymes (corresponding to about 10% of the cytosolic protein) a significant inhibition of the rate of hydrolysis is observed, indicating a physical interaction between the diol epoxide and GST. This is compatible with the proposed role of certain GST-isoenzymes as intracellular carriers for lipophilic compounds. Studies on the accessibility of (+)- anti-BPDE to hydrolysis and GST-catalysed conjugation with GSH reveal that the presence of rat liver microsomes or liposomes, in particular those composed of the neutral phospholipids, phosphatidylcholine (PC) and phosphatidylethanolamine (PE), very effectively protect the diol epoxide from hydrolysis. Addition of cytosolic fraction depleted of GST to a mixture of GST-isoenzymes and microsomes or liposomes do not significantly increase the rate of GSH-conjugation. This implies the absence of high molecular factors in the cytosol that may increase the accessibility of (+)- anti-BPDE and thus promote conjugation. In contrast to liposomes of PC and PE, those composed of the negatively charged phospholipids phosphatidylserine (PS) and phosphatidylinositol (PI) are considerably less efficient in protecting (+)- anti-BPDE. In fact, these lipids seem to promote hydrolysis, an effect which is lost when PS and/or PI are present together with PC and PE. Taken together, the results presented here suggest that (+)- anti-BPDE and most probably other diol epoxides, are not accessible for GSH-conjugation by direct interaction between GST and the membrane-bound compound. Moreover, there is little support for the existence of cytosolic components that increase the accessibility of (+)- anti-BPDE for conjugation. In agreement with previous results using other compounds, the results indicate that only the fraction of diol epoxide that is free in solution is accessible for conjugation with GSH.

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