Inactivation of cytochrome P-450 by 2-isopropyl-4-pentenamide and other xenobiotics leads to heme-derived protein adducts

Chem Biol Interact. 1986 Jun;58(3):345-52. doi: 10.1016/s0009-2797(86)80108-9.


When cytochrome P-450 in phenobarbital-induced rat liver microsomes was destroyed by 2-isopropyl-4-pentenamide (AIA) in vitro, 50% of the degraded heme was recovered as heme-derived products irreversibly bound to microsomal proteins. In contrast, less than 50% of the degraded heme was accounted for as N-alkylated porphyrins. Furthermore, 64% of the irreversibly bound products was bound specifically to a 54-kD form of cytochrome P-450. Several other compounds which have been reported to destroy cytochrome P-450 by forming N-alkylated porphyrins also produced heme-derived protein adducts. These findings indicate that the formation of heme-derived protein adducts may represent an important pathway for the irreversible degradation of cytochrome P-450 by many xenobiotics.

MeSH terms

  • Acetamides / pharmacology*
  • Allylisopropylacetamide / pharmacology*
  • Animals
  • Cytochrome P-450 Enzyme Inhibitors*
  • Heme / analysis*
  • Male
  • Microsomes, Liver / metabolism*
  • NADP / metabolism
  • Porphyrins / analysis
  • Protein Binding
  • Proteins / analysis*
  • Rats
  • Rats, Inbred Strains


  • Acetamides
  • Cytochrome P-450 Enzyme Inhibitors
  • Porphyrins
  • Proteins
  • Allylisopropylacetamide
  • Heme
  • NADP