Enzymatic deficiencies of purine nucleotide synthesis in the human erythrocyte.

In the development of the mature rabbit erythrocyte from the reticulocyte, the capacity for the synthesis de novo of the purine ring in vitro is lost (2, 3). The mature rabbit erythrocyte, however, does retain a portion of the biosynthetic pathway de novo, as evidenced by its utilization of 5-amino-1-ribosylWimidazolecarboxamide and sodium formate-Cl4 for the formation of inosinic acid (4). The inosinic acid can then be converted to adenosine triphosphate and guanosine triphosphate in vitro by the known metabolic routes. The mature rabbit erythrocyte is also capable of utilizing a number of purines and their ribosyl derivatives for the formation of the triphosphates of adenosine and guanosine (5). In recent years, it has been demonstrated that inosine and other purine nucleosides delay the changes that occur in erythrocytes during storage, i.e. the decrease in the concentrations of adenosine triphosphate and other organic phosphates (6), the loss of potassium ion from the cell (7), the change in biconcave shape (8), the increased susceptibility to osmotic lysis (9), and the decline in post-transfusion viability (10). The addition of some purine nucleosides to cells in which these changes are already detectable results in appreciable reversal of these manifestations of erythrocyte degeneration. It has been suggested, therefore, that the addition of a purine nucleoside to the usual preservative medium for the storage of blood might extend the period of viability of the stored erythrocytes (10). Although significant prolongation of survival of rabbit erythrocytes has been achieved with the addition of inosine alone (lo), the addition of a purine nucleoside to human erythrocytes has resulted in only a very slight improvement in post-transfusion viability (11, 12). In this report, the normal mature human erythrocyte is shown to resemble the rabbit cell in its inability to synthesize the purine portion of adenosine triphosphate from the purine ring precursors and in its ability to carry out the final steps of purine ring formation. In contrast to the rabbit erythrocyte, however, the human erythrocyte has little, if any, capacity for the conversion of inosinic acid to the adenine nucleotides.