Effect of testosterone on purine nucleotide metabolism in rat liver

In previous studies, we found that castration induced interesting morphological and biochemical changes in rat liver. For the present study, we have examined the effects of testosterone on the kinetics of purine nucleotide metabolism with the aim of determining the steps affected by testosterone deficiency. A biomathematical model of purine nucleotide metabolism was used to analyze the many reactions involved. The model simplifies purine nucleotide metabolism to four main steps: 1) de novo synthesis from PRPP to IMP; 2) the inosinic branch point from IMP to GMP or AMP; 3) catabolism of IMP, AMP and GMP to uric acid; 4) RNA and DNA formation from AMP and GMP. We evaluated rate constants from each step from variations in specific radioactivity of metabolites labelled with (14)C-formate, a precursor of de novo synthesis. The model was applied to the liver of normal and castrated rats before and after testosterone treatment. All four steps were slowed after castration, and were not completely restored by androgen administration. The model can give a clear representation of the kinetics of the reactions involved in the liver nucleotide metabolism investigated here, and we propose that a similar approach could be useful whenever a quantitative evaluation of the results obtained in vivo after administration of labelled precursors is required