The effect of age on the oxidative metabolism of antipyrine by uninduced microsomal fractions of rat liver.
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.
Van Geel
C A
CA
TNO Institute for Experimental Gerontology, Rijswijk, The Netherlands.
Van Bezooijen
C F
CF
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
D007527:Isoenzymes; C007983:4-hydroxyantipyrine; C031820:3-hydroxymethylantipyrine; D003577:Cytochrome P-450 Enzyme System; D000077553:Edaravone; D000983:Antipyrine