Liver nucleotide metabolism in relation to amino acid supply

Abstract

Changes in the purine nucleotide metabolism of rat liver resulting from diurnal variations in food intake, from fasting and from consuming meals of protein have been correlated with alterations in liver polysome abundance and RNA content. De novo purine synthesis, measured by [ 14C]glycine incorporation into free adenine and guanine nucleotides, was considerably stimulated by protein-containing meals and conversely underwent a decrease following a 12-h period of fasting. In addition, protein-containing meals caused a small decrease in the concentration of free adenine and guanine nucleotides in the liver and fasting resulted in a transient increase in these nucleotides, but these nucleotide changes were eliminated as factors regulating activity in the de novo pathway because they occurred some hours after alterations were evident in purine biosynthesis. Under the various nutritional conditions used, no significant changes could be detected in the liver content of the first enzyme of the de novo pathway, phosphoribosyl pyrophosphate amidotransferase, or in the levels of its substrates phosphoribosyl pyrophosphate and glutamine. Consequently, the control mechanism regulating purine biosynthesis in response to changes in amino acid supply could not be identified. However, there was a close correlation between alterations in purine biosynthesis and changes in the state of polysome aggregation. It is suggested that amino acid-dependent alterations in polysome aggregation determine the rate of RNA breakdown and that an unidentified product of RNA degradation regulates purine biosynthesis.