A Role of Liver Adenosine in the Renewal of the Adenine Nucleotides of Human and Rabbit Erythrocytes

Abstract

For many years the work of our laboratory has been concerned with the synthesis and metabolism of the purine nucleotides in the mature human and rabbit erythrocyte and in the rabbit reticulocyte. Our early studies (1–5) and those of Mager’s group (6,7) and others (8) have demonstrated the metabolic renewal of the purine nucleotides within the circulating erythrocyte during its lifespan. The observed turnover occurs in the absence of the capacity for the de novo biosynthetic pathway in the erythrocytes of both species, although the cells do contain purine nucleoside phosphorylase as well as adenine phosphoribosyltransferase and hypoxanthine-guanine phosphoribosyltransferase. However, the human erythrocyte lacks adenylosuccinate synthetase (9) and thus is unable to convert IMP to AMP, an enzymatic capacity possessed by the rabbit red cell. The erythrocytes of both species do possess adenylosuccinase and can, therefore, convert adenylosuccinate to AMP, and succinylaminoimidazolecarboxamide ribotide to aminoimidazolecarboxamide ribotide (AICAR). Formylation of AICAR and ring closure, which can occur in the erythrocyte, then leads to IMP formation. We had reported some years ago that the loss of a portion of the de novo pathway accompanies the maturation of the rabbit reticulocyte (4). More recent studies have indicated that many of the enzymes required for the early steps of the pathway are lacking in the erythrocytes of both species (10).