Effects of lipid peroxidation on activities of drug-metabolizing enzymes in liver microsomes of rats

A relationship was found between the formation of lipid peroxides and the activities of drug-metabolizing enzymes in liver microsomes of rats. Induction of lipid peroxidation by incubation with ferrous ion led to a sharp decline in the ability of the microsomal enzyme system to demethylate ethylmorphine. Inhibition of lipid peroxidation by EDTA increased the enzyme activity about two-fold. Addition of EDTA (0.1 mM) to the incubation mixture produced marked changes in the Michaelis constants of drug-metabolizing enzymes and in inhibition constants of SKF 525-A for drug-metabolizing enzymes.