Suicidal Inactivation of Cytochrome P-450 by Halothane and Carbon Tetrachloride
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.
KeywordsCarbon Tetrachloride Dimethyl Ester Partition Ratio Anaerobic Incubation Reductive Metabolism
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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© Plenum Press, New York 1991