The effect of age on the oxidative metabolism of antipyrine by uninduced microsomal fractions of rat liver
article
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. 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 the different P-450 isoenzymes involved in antipyrine metabolism, in different ways. However, the age-related changes are modest (10-100%), especially for the V(max)/K(m) ratio.
Topics
AgeAntipyrineDrug metabolismMicrosomesRatphenazoneadolescentageagedanimal cellarticlecontrolled studydrug metabolismliver microsomemalenonhumanpriority journalratAgingAnimalAntipyrineCytochrome P-450 Enzyme SystemIn VitroIsoenzymesKineticsMaleMicrosomes, LiverOxidation-ReductionRatsRats, Inbred BNAnimalia
TNO Identifier
231141
ISSN
00476374
Source
Mechanisms of Ageing and Development, 53(2), pp. 169-177.
Pages
169-177
Files
To receive the publication files, please send an e-mail request to TNO Repository.