title: The effect of age on the oxidative metabolism of antipyrine by uninduced microsomal fractions of rat liver.
abstract: The influence of ageing on the metabolism of antipyrine by different forms of cytochrome P-450 was studied in vitro, by measuring the formation of antipyrine metabolites by microsomes isolated from untreated rats, which were grouped into 5 different ages. Km, Vmax and Vmax/Km values were determined for the metabolites: 3-hydroxymethylantipyrine (HMA), norantipyrine (NORA) and 4-hydroxyantipyrine (OHA). Km values for all metabolites ranged from 2.0 to 5.0 mM and Vmax values from 1.84 to 3.66 nmol/min per mg. The Vmax/Km ratios varied from 0.65 to 1.73 microliters/min per mg. With respect to the Km values, a decrease for HMA from 12 to 24 months, no change for OHA and an increase for NORA from 3 to 30 months, was observed. The Vmax values showed an increase for HMA from 3 to 24 months, a decrease for OHA from 12 to 30 months and no change for NORA. The absolute Vmax/Km ratios for all metabolites showed no significant changes during ageing. However, regarding the relative Vmax/Km ratios, an increase for HMA from 3 to 24 months, a decrease for OHA from 12 to 35 months and also a decrease for NORA from 3 to 24 months, was observed. It is concluded that ageing influenced the Km, Vmax and Km/Vmax ratio of the different P-450 isoenzymes involved in antipyrine metabolism, in different ways. However, the age-related changes are modest (10-100%), especially for the Vmax/Km ratio.
authors.affiliation: TNO Institute for Experimental Gerontology, Rijswijk, The Netherlands.
authors.forename: C A
authors.initials: CA
authors.lastname: Van Geel
authors.forename: C F
authors.initials: CF
authors.lastname: Van Bezooijen
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D000077553:Edaravone; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D011914:Rats, Inbred BN
chemical_list: D007527:Isoenzymes; C007983:4-hydroxyantipyrine; C031820:3-hydroxymethylantipyrine; D003577:Cytochrome P-450 Enzyme System; D000077553:Edaravone; D000983:Antipyrine