Mechanism of increased rate of de novo purine biosynthesis in rat liver after bilateral adrenalectomy

Abstract

The incorporation of [14C]glycine to hepatic purines increased proving the increased rate of de novo purine biosynthesis in rat liver after bilateral adrenalectomy in comparison to sham-operated controls. In the liver of adrenalectomized animals 24 hours after adrenalectomy when the rate of de novo purine biosynthesis is increased above control by 70% there was a 200% increase of 5-phosphoribosyl 1-pyrophosphate (PRPP) concentration. The concentrations of purine ribonucleotides showed a 33 and a 24% decrease of ATP and GTP, and 245 and 38% increase of AMP and ADP respectively associated with the unchanged total adenine and guanine nucleotide concentration and a 18% decrease of adenylate energy charge. The specific activity of amidophosphoribosyltransferase (ATase) was not changed. The replacement with corticosterone acetate to adrenalectomized animals for 24 hours partially restored the rate of de novo purine biosynthesis and the concentrations of purine ribonucleotides. These results suggest that the increased rate of de novo purine biosynthesis in adrenalectomized rat liver is compensatory against the increased catabolism of purine ribonucleotides as a result of the increased AMP concentration and that it is mediated by the increased concentration of PRPP. Our study has demonstrated the importance of the physiological amount of adrenocortical hormone to sustain the normal concentrations and the metabolism of purine ribonucleotides in liver.