The inhibitory effect of reduced glutathione on the lipid peroxidation of the microsomal fraction and mitochondria.

1. GSH efficiently inhibited the ascorbate-stimulated lipid peroxidation of the unsaturated fatty acids in the fresh microsomal fraction and mitochondria of rat liver, whereas the peroxidation in heat-denatured particles was little inhibited. 2. Cysteamine and diethyldithiocarbamate inhibited the peroxidation in both fresh and boiled particles. Thioglycollate and 2-mercaptoethanol had no inhibiting effect. Cysteine and homocysteine both stimulated the lipid peroxidation even in the absence of ascorbate. 3. The added GSH disappeared at nearly the same rate in the presence of fresh and of boiled particles to which ascorbate had been added, although considerably more malonaldehyde was formed in the boiled particles. In the absence of ascorbate little GSH disappeared. 4. It is suggested that the protective effect of GSH against lipid peroxidation depends on the preservation of heat-labile structures in the microsomal fraction and mitochondria.