Carbon tetrachloride and 2-isopropyl-4-pentenamide-induced inactivation of cytochrome P-450 leads to heme-derived protein adducts

Arch Biochem Biophys. 1986 Jan;244(1):387-92. doi: 10.1016/0003-9861(86)90128-1.


When CCl4 was incubated with rat liver microsomes from phenobarbital-treated rats in an aerobic or anaerobic atmosphere, over 69% of the heme moiety of cytochrome P-450 was destroyed. At least 45% of the degraded heme under both reaction conditions was accounted for as heme-derived products irreversibly bound to microsomal proteins. Furthermore, 33% of the irreversibly bound products were bound specifically to a 54-kDa form of cytochrome P-450. A structurally different compound, 2-isopropyl-4-pentenamide, also destroyed the heme moiety of cytochrome P-450 and produced heme-derived adducts of microsomal proteins that accounted for 28% of the destroyed heme. These results represent a novel mechanism for the destruction of cytochromes P-450 by xenobiotics.

MeSH terms

  • Acetamides / pharmacology*
  • Allylisopropylacetamide / pharmacology*
  • Animals
  • Binding Sites
  • Carbon Tetrachloride / pharmacology*
  • Cytochrome P-450 Enzyme Inhibitors*
  • Electrophoresis / methods
  • Heme / metabolism*
  • Immunochemistry
  • In Vitro Techniques
  • Male
  • Microsomes, Liver / enzymology
  • Protein Binding
  • Proteins / metabolism*
  • Rats


  • Acetamides
  • Cytochrome P-450 Enzyme Inhibitors
  • Proteins
  • Allylisopropylacetamide
  • Heme
  • Carbon Tetrachloride