Activation of Cytochrome P-450 Heme in Vivo

  • Helen W. Davies
  • Paul E. Thomas
  • Lance R. Pohl
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 197)


It is well known that the administration of CC14 produces substantial decreases in the activities of cytochromes P-450 in the liver as well as in other organs. 1–5 The inactivation.s most likely due to the observed destruction of cytochrome P-450 heme,1 but neither the mechanism nor the products of that destruction have been elucidated. It has been found in the present study that the pathway of the CC14 inactivation of rat liver cytochromes P-450 in vivo includes the irreversible binding of heme-derived products to microsomal proteins and that a large fraction of the irreversibly bound heme-derived products are attached specifically to cytochromes P-450. These findings suggest that CC14 destroys cytochromes P-450, at least in part, by producing activated heme moieties which subsequently bind irreversibly to cytochrome P-450 protein. In addition, the levels of two cytochrome P-450 isozymes in microsomes are decreased following CC14 treatment. It may be that the irreversible binding of heme fragments functions as a signal for proteolytic degradation of cytochrome P-450 proteins.


Carbon Tetrachloride Liver Microsome Microsomal Protein Irreversible Binding Heme Moiety 
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Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Helen W. Davies
    • 1
  • Paul E. Thomas
    • 2
  • Lance R. Pohl
    • 1
  1. 1.Laboratory of Chemical PharmacologyNational Heart, Lung, and Blood Institute, National Institutes of Health BethesdaUSA
  2. 2.Laboratory of Experimental Carcinogenesis and MetabolismRoche Institute of Molecular BiologyNutleyUSA

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