Purine de novo Synthesis in Liver and Developing Rat Brain, and the Effect of Some Inhibitors of Purine Nucleotide Inter con version

Publisher Website
Google Scholar
Abstract
The rate of purine de novo synthesis from sodium formate in developing rat brain falls in the late gestational stages to birth, rises again in the 1st wk of life and then decreases rapidly to the 3rd wk, and continues declining up to 8 wk of life (adulthood). The changes in the overall purine biosynthetic rate with respect to time are similar to those in the activity of the rate-limiting enzyme [amidophosphoribosyltransferase, EC 2.4.2.14]. Azaserine [O-diazoacetyl-L-serine], a known inhibitor of glutamine requiring metabolic steps, inhibits purine de novo synthesis by more than 90%. This confirms that the method used to assess purine de novo synthesis in fact does so. The effects of virazole [1-.beta.-ribofuranosyl-1-H,1,2,4-triazole-3-carboxamide], an inhibitor of IMP dehydrogenase (EC 1.2.1.14), and of alanosine [L-2-amino-3-(hydroxynitrosamino)propanoic acid] an inhibitor of adenylosuccinate synthetase (EC 6.3.4.4), on the rate of purine de novo synthesis were investigated in liver and brain tissue. The effect of the xanthine oxidase inhibitor allopurinol [4-hydroxypyrazolo(3,4-d)pyrimidine] was also investigated in liver tissue. The biosynthesis of the purines which were extruded into the incubation medium as well as those which remained in the tissue was studied. Only inhibitory effects were observed, and these were confined to the purines remaining in the tissue. Allopurinol was completely inert from this viewpoint. The results are compared with those of other workers using lymphoid cells, and emphasize the differences in the control of de novo purine synthesis in different tissues and under different conditions. They raise the possibility of a functional compartmentalization of purines destined for export from the cell from those destined for use within the cell.