Age-related changes in hepatic microsomal drug metabolism are substrate selective.
Microsomes were isolated from livers of male Fischer 344 rats at 3 to 5, 14 to 15 and 24 to 25 months of age for the determination of monooxygenase components and drug metabolism activities. Microsomal cytochrome P-450, cytochrome b5, NADPH-cytochrome c reductase activity and phospholipid were decreased in middle-aged and old rats compared with young-adult rats, but the enzymatic reduction of microsomal cytochrome P-450 was unchanged. Drug metabolism activities both decreased and increased as a consequence of aging, depending upon the substrate used. Differences were observed between young-adult and old rats in the CO maximum of reduced microsomal cytochrome P-450, in microsomal fatty acid composition and in the amounts of microsomal polypeptides having molecular weights of 52,500 and 53,000. The substrate selectivity of the age-related alterations in hepatic microsomal drug metabolism may be due to qualitative changes in the cytochrome P-450 and phospholipid components of the monooxygenase system.
D000375:Aging; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D066298:In Vitro Techniques; D050356:Lipid Metabolism; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D006899:Mixed Function Oxygenases / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D013379:Substrate Specificity
D005227:Fatty Acids; D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases