Loss of Liver Cytochrome P-450 Caused by Chemicals

Damage to the Apoprotein and Degradation of the Heme Moiety
  • F. De Matteis
Part of the Handbuch der experimentellen Pharmakologie / Handbook of Experimental Pharmacology book series (HEP, volume 44)


The most common response of the liver to the administration of foreign chemicals is an increase in the concentration of its hemoproteins (especially that of cytochrome P-450); this is one aspect of the more general adaptive response, usually referred to as induction of the drug-metabolizing system, which has been dealt with by Bock and Remmer in Chapter 2. There are cases, however, in which a chemical causes a decrease rather than an increase in the concentration of the hemoproteins of the liver, and this may result from an inhibition of their formation, from an increase in the rate of their degradation, or, finally, from a combination of these two mechanisms. Compounds which are thought to act by inhibiting heme synthesis have been discussed by Tephly in Chapter 3. The purpose of this paper is to consider in detail the effects of those chemicals that increase the rate of degradation of heme and hemoproteins in the liver. In the discussion of these effects, one particular hemoprotein—cytochrome P-450—will figure prominently. This is partly because this hemoprotein has attracted a great deal of interest in the last few years, and it is also easy to measure, so it has been extensively studied in several laboratories; also, cytochrome P-450 is particularly liable to toxic damage by a number of chemicals, apparently much more liable than the other hemoproteins of the liver, including the other cytochrome of the endoplasmic reticulum, cytochrome b5. This is due to the properties peculiar to cytochrome P-450 of interaction with several classes of potentially toxic chemicals.


Carbon Tetrachloride Liver Microsome Heme Oxygenase Green Pigment Carbon Disulphide 
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© Springer-Verlag Berlin Heidelberg 1978

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  • F. De Matteis

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