Spectral interactions of a series of chlorinated hydrocarbons with cytochrome P ‐450 of liver microsomes from variously‐treated rats

The cytochrome P-450~linked mono-oxygenase system which resides in the liver microsomes and also in other tissues metabolizes a vast number of foreign as well as endogenous compounds, including drugs, steroids, pesticides etc. [ 11. The pre-requisite for the metabolism is supposed to be a binding of substrate to oxidized cytochrome P-450 which is often observable in the difference spectrum of the microsomes as a type I spectral change, characterized by a trough at about 420 nm and a peak at about 390 nm [2,3]. Because the cytochrome P-450~linked monooxygenase system of liver microsomes is very unspecific with respect to metabolizable substrates there have been attempts to find common properties for the heterogeneous group of cytochrome P-450 substrates. Gaudette and Brodie [4] were first to point out that there appears to be a direct relationship between the rate of microsomal metabolism and the lipophilic character of drugs. Later, McMahon [5] and Martin and Hansch [6] found rough correlations between lipid solubility and metabolism by the cytochrome P-450 system for various groups of compounds. On the other hand, other studies that although lipid solubility may be required for a substance to be metabolized by, and to interact with microsomal cytochrome P-450, other properties of the molecule, e.g. stereoselectivity, are of major importance for determining the affinity with which it will interact with the cytochrome [7-91. In the present study, a series of chlorinated hydrocarbons, methanes, ethanes, ethanes have been studied with respect to spectral interactions with cytochrome