The Mechanism of Insulin-Induced Increase of the Rate of De Novo Purine Biosynthesis in Primary Cultured Rat Hepatocytes

Abstract

The effect of insulin on the rate of de novo purine biosynthesis was studied in freshly isolated hepatocytes from adult male rats. Insulin started to increase the rate of de novo purine biosynthesis at 1.5 X 10(-10) M and plateaued at 1.5 X 10(-8) M with the magnitude of increase of about 280%. Insulin at 1.5 X 10(-9) M or the higher concentration increased the 5-phosphoribosyl 1-pyrophosphate (PRPP) availability for purine ribonucleotide synthesis to about 230%. Insulin increased ATP concentration to 127% and decreased AMP, ADP, GMP and GDP concentration to 73, 69, 73 and 69% in association with the increased adenylate energy charge of 0.90 in comparison to the control level of 0.83. But the total adenine and guanine nucleotide concentration in the cell was not significantly changed. In addition insulin increased the specific activity of amidophosphoribosyltransferase (ATase) with the increased Vmax and the unchanged Km for PRPP.