ROLE OF SUBSTRATE LIPOPHILICITY IN DETERMINING TYPE-1 MICROSOMAL P450 BINDING CHARACTERISTICS

The Type 1 cytochrome P450 binding of 53 aliphatic, alicyclic and aromatic compounds to microsomes from phenobarbitone or 3 methylcholanthrene pre-treated or normal hamsters has been studied. A good correlation between binding affinity and substrate lipophilicity was observed for each series of compounds. Sterically hindered molecules tended to partially deviate from this relationship. The pronounced slopes of plots of Ks against log P indicate that substrate lipophilicity is the predominant requirement for Type 1 binding of these compounds. Microsomes from phenobarbitone pre-treated animals showed very similar substrate binding characteristics to those of normal animals whilst 3-methylcholanthrene pre-treated animals showed a spectral shift but similar binding affinities. © 1978.