AGE-RELATED-CHANGES IN HEPATIC-MICROSOMAL DRUG-METABOLISM ARE SUBSTRATE SELECTIVE

  • 1 January 1982
    • journal article
    • research article
    • Vol. 220  (3) , 574-578
Abstract
Microsomes were isolated from livers of male Fischer 344 rats at 3-5, 14-15 and 24-25 mo. 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 MW of 52,500 and 53,000. The substrate selectivity of the age-related alterations in heptic microsomal drug metabolism may be due to qualitative changes in the cytochrome P-450 and phospholipid components of the monooxygenase system.