The effect in vivo and in vitro of allylisopropylacetamide on the content of hepatic microsomal cytochrome P-450 2 of phenobarbital treated rabbits.
Rabbits treated with phenobarbital were given a single injection of allylisopropylacetamide (AIA) s.c. and/or heme i.v. Hepatic microsomes were isolated 1, 5 and 24 hours post injection and the microsomal contents of both total cytochrome P-450 chromophore, and the protein moiety of P-450 2 were determined by spectrophotometric and immunochemical methods respectively. AIA caused the levels of total P-450 chromophore and of P-450 2 protein to decline to 30% of the control values at 5 hours post-injection. Concurrent administration of heme with AIA diminished the decrease in the total microsomal content of P-450 chromophore but not in that of P-450 2 protein. These findings suggest that the destruction of the heme prosthetic group of P-450 by suicide substrates such as AIA may lead to an enhanced degradation of the apo-P-450.
D000081:Acetamides / Q000494:pharmacology*; D000502:Allylisopropylacetamide / Q000494:pharmacology*; D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D003577:Cytochrome P-450 Enzyme System / Q000302:isolation & purification*; D006418:Heme / Q000494:pharmacology; D066298:In Vitro Techniques; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D009249:NADP / Q000494:pharmacology; D010634:Phenobarbital / Q000494:pharmacology*; D011817:Rabbits
D000081:Acetamides; D000502:Allylisopropylacetamide; D006418:Heme; D009249:NADP; D003577:Cytochrome P-450 Enzyme System; D010634:Phenobarbital