Studies on age related changes in cytochrome P-450, cytochrome b-5 and mixed function oxidase activity in mouse liver microsomes, in relation to their phospholipid composition

Liver microsomes were isolated from male mice of various defined ages, and their ability to metabolise ethylmorphine, p-nitroanisole, p-aminobenzoic acid and aniline was assessed as was their content of cytochrome P-450, cytochrome b-5 and protein, and their lipid composition. The rising capacity of the microsomes to metabolise these substrates in the first half of the lifespan was associated with a rise in the cytochrome P-450 and cytochrome b-5 content as well as an increase in the ratio of phosphatidylcholine to both phosphatidylethanolamine and sphingomyelin and, in early adult life, decreasing saturation of phospholipid fatty acids. The lipid changes would be expected to increase microsomal membrane fluidity. Declining mixed function oxidase activity in later life paralleled a decline in the ratio of phosphatidylcholine to phosphatidylethanolamine and sphingomyelin, and progressively reduced saturation of phospholipid fatty acids. Cytochrome content showed only a slight irregular decline with advancing age until the oldest animals were investigated, in which cytochrome b-5 was considerably reduced. Unfortunately, cytochrome P-450 was not measured in the oldest available group. Inducing the mixed function oxidase system with daily phenobarbitone injections for 4 days substantially increased enzyme activity in animals up to the middle of the age range tested. Older animals showed progressively reduced induction and none at all was seen in the oldest group. In contrast with the situation in non-induced mice, these changes were more closely associated with changes in cytochrome P-450 content than with alterations of lipid composition.