PMID: 6408319Feb 1, 1983Paper

Age-dependent alterations in rat liver microsomal NADPH-cytochrome c (P-450) reductase: a qualitative and quantitative analysis

Mechanisms of Ageing and Development
D L Schmucker, R K Wang

Abstract

The hepatic drug-metabolizing capacities of rodents and man exhibit age-dependent declines. The extensive use of medication in geriatric patients demonstrates the need to characterize the mechanism(s) responsible for this reduced liver function. An analysis of microsomal NADPH-cytochrome c (P-450) reductase in young adult (3 months), mature (9 months) and senescent (27 months) male Fischer 344 rats revealed specific age-related qualitative and quantitative changes in this enzyme. The specific activity of the purified enzyme from young animals was two-fold higher than that recovered from the other age groups. In addition, there was: (1) no change in molecular weight, (2) alterations in heat inactivation profiles, (3) an apparent reduction in substrate affinity, and (4) a two-fold loss of enzyme activity per unit of immunoprecipitable material as a function of animal age. Our data suggest that this important liver drug-metabolizing enzyme undergoes post-translational modifications in its conformation which are reflected in the above parameters and which, ultimately, affect its efficacy.

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Citations

Oct 15, 1984·Mechanisms of Ageing and Development·D L SchmuckerA Maloney
Aug 1, 1984·Mechanisms of Ageing and Development·A A Okada, J F Dice
Oct 1, 1988·Mechanisms of Ageing and Development·M Nakano, H Tauchi
Oct 1, 1986·Archives of Gerontology and Geriatrics·C Santa Maria, A Machado
Mar 1, 1991·Archives of Gerontology and Geriatrics·K Kitani
Jan 1, 1990·Experimental Gerontology·D L Schmucker
Feb 7, 2004·Archives of Gerontology and Geriatrics·Douglas L Schmucker, Howard Sachs
Nov 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·K C Yuh, A Gafni
Jan 1, 1988·Experimental Aging Research·D G Hazzard, J Soban
Oct 8, 2008·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Lu GanMichael H Court
Aug 17, 2005·Experimental Gerontology·Douglas L Schmucker
Nov 1, 1988·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·C P Chengelis
Jan 1, 1987·Journal of the American Geriatrics Society·L S Birnbaum
Feb 1, 1984·Journal of the American Geriatrics Society·D L Schmucker
Jun 3, 2014·Pharmacology & Therapeutics·Payman ShahabiSophie Visvikis-Siest
Apr 1, 1992·Biopharmaceutics & Drug Disposition·J H Satterwhite, F D Boudinot
Feb 1, 1990·Journal of Electron Microscopy Technique·D L Schmucker
Mar 1, 1986·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·K Kitani
Dec 5, 2017·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Khaled A ShibanyStuart W Paine
Mar 1, 1986·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·A G MaloneyR K Wang
May 11, 2002·Infection Control and Hospital Epidemiology : the Official Journal of the Society of Hospital Epidemiologists of America·Christopher S HollenbeakVictoria J Fraser
May 18, 2016·Journal of Dairy Science·C A WolfJ C Swanson
Jul 12, 2017·International Journal of Environmental Research and Public Health·Anabela BotelhoLígia M Costa Pinto
Jun 1, 1988·Journal of Clinical Pharmacology·B J Cusack

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