Spectral Studies of Drug Interaction with Hepatic Microsomal Cytochrome

Abstract

Two types of spectral changes are described as resulting from substrate interaction with a hepatic microsomal cytochrome; the magnitude of these spectral changes is dependent on protein concentration and substrate concentration as well as the substrate employed. In two of the three types of substrates examined, the concentration of substrate necessary to evoke half-maximal enzyme activity was similar to the concentration of the same substrate necessary for half-maximal spectral changes. The addition of NADPH, a corequirement for the microsomal mixed function oxidase, causes a modification of both types of spectral changes, without altering substrate affinity. Three possible hypotheses are advanced, based upon the experimental observations, to explain the two types of spectral changes observed.