Suicidal Inactivation of Cytochrome P-450 by Halothane and Carbon Tetrachloride

  • Maurizio Manno
  • Michela Rezzadore
  • Stefano Cazzaro
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 283)


The reductive metabolism of carbon tetrachloride (CCl4) and halothane (H) by liver microsomal cytochrome P-450 leads to the formation of reactive intermediates and results in the inactivation of the enzyme and loss of its prosthetic group haem (de Groot H. et al., 1981; Krieter P.A. et al., 1983). Previous work has shown that the haem moiety is the critical target of CCl4 and H activation by cytochrome P-450, indicating that, with both substrates, a suicide type of reaction is probably involved (Manno M., et al., 1988; Manno M., et al., 1989). Indeed, haem alone, in the absence of the apoprotein, was able to undergo CCl4- or H-dependent suicidal inactivation when incubated anaerobically with each substrate in presence of a reducing agent (Manno, M., et al., 1989; Manno M., 1989). The CCl4dependent loss of haem is due to attack by a single reactive metabolite molecule (Manno, M., et al., 1989). In the present study we compared the mechanisms of the suicidal, reductive inactivation of cytochrome P-450 by CCl4 and H.


Carbon Tetrachloride Dimethyl Ester Partition Ratio Anaerobic Incubation Reductive Metabolism 
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Abbreviations used








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Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Maurizio Manno
    • 1
  • Michela Rezzadore
    • 1
  • Stefano Cazzaro
    • 1
  1. 1.Institute of Occupational MedicineUniversity of Padua Medical SchoolPadovaItaly

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