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 formatin of antipyrine metabolites by microsomes isolated from untreated rats, which were grouped into 5 different ages. K m , V max and V max / K m values were determined for the metabolites: 3-hydroxymethylantipyrine (HMA), norantipyrine (NORA) and 4-hydroxyantipyrine (OHA). K m values for all metabolites ranged from 2.0 to 5.0 mM and V max values from 1.84 to 3.66 nmol/min per mg. The V max/ K m ratios varied from 0.65 to 1.73 μl/min per mg. With respect to the K m 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 V max 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 V max/ K m ratios for all metabolites showed no significant changes during ageing. However, regarding the relative V max/ K m 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 K m , V max and K m / V max ratio of different P-450 isoenzymes involved in antipyrine metabolism, in different ways. Howevers, the age-related changes are modest (10–100%), especially for the V max/ K m ratio.