SUBSTRATE INTERACTION WITH MICROSOMAL CYTOCHROME P-450

Publisher Summary This chapter discusses about substrate interaction with microsomal cytochrome P-450. Cytochrome P-450 is the terminal oxidase involved in a number of NADPH-linked microsomal hydroxylation (monooxygenase) reactions. The spectral studies on the interaction of various substrates with microsomal cytochrome P-450 are reported. Imipramine is a tricyclic compound, which upon incubation with rat-liver microsomes in the presence of NADPH and O 2 gives rise to the formation of 2-hydroxyimipramine and desmethylimipramine (DMI). The type I spectral change obtained with imipramine, DMI and 2-OH-DMI reflects the interaction of the compounds with the same cytochrome P-450 species is shown by the experiments. Evidence for the relationship between the type I spectral change and oxidative metabolism comes from the finding that the calculated binding constants of various substrates parallel their apparent Michaelis constants.