De Novo Synthesis of Myocardial Adenine Nucleotides in the Rat

Abstract

De novo synthesis of adenine nucleotides was measured in rat hearts in situ and in isolated perfused rat hearts under normal conditions and during recovery from asphyxia or ischemia. Using l-¹⁴C-glycine as the precursor substrate, rates of de novo synthesis were determined from the total radioactivity of adenine nucleotides and from the mean specific activity of intracellular glycine. The rate of de novo synthesis of adenine nucleotides was 8.4±1.42 nmoles/g hour^-1 in the heart in situ and 1.3±0.12 nmoles/g hour^-1 in the isolated perfused heart. De novo synthesis of adenine nucleotides increased almost 100% in the heart in situ and about 580% in the isolated perfused heart during the first hour of recovery from asphyxia or ischemia. This acceleration is regarded as an adaptive process contributing to the postanoxic restoration of normal adenine nucleotide levels. Possible biochemical mechanisms that might be involved in the stimulation of the de novo pathway are a release of feedback inhibition of 5-phosphoribosyl-1-pyrophosphate amidotransferase, an enhanced synthesis of 5-phosphoribosyl-1-pyrophosphate, and an alternate way of 5-phosphoribosyl-amine formation.