[Identification of various hydrophobic zones in microsomal membranes containing cytochrome P-450 binding sites for type I and II substrates]

Abstract

Two different phospholipid hydrophobic zones in the membrane associated with cytochrome P-450 were identified. One of them exhibits selective sensitivity towards the protonated influence of carbonylcyanide-m-chlorophenyl hydrazone and possesses binding sites for type I substrates. The second one includes the heme group of cytochrome P-450 and herein the binding sites for type II substrates. Sodium deoxycholate (0.75-2.0 mM) disrupts both zones. Subsequent incorporation of fluorine atoms into a type II substrate (aniline) results in the increase in the hydrophobicity of aniline halogenated derivatives and in changes in the substrate-binding sites for tetra- and pentafluoroanilines from the heme-iron sphere to the apoenzyme of cytochrome P-450.