Enhanced purine nucleotide synthesis in erythrocytes of uremic patients.

Abstract

Studies were performed which suggest that the increased red cell levels of ATP and adenine nucleotides in uremic patients may be secondary to an increased biosynthetic rate of adenine nucleotides via salvage pathway by the predominance of younger red cells. Both normal and uremic red cells were separated in three groups according to their age by centrifugation in a discontinous density gradient using phthalate esters as separating liquids. 1. The uremic subjects have a substantial reduction of the older (more dense) red cells with a 3–4 fold increase of the younger red cells. 2. The specific activity of the salvage pathway enzymes phosphoribosyl-1-pyrophosphate (PRPP)-synthetase, adenine phosphoribosyltransferase and the red cell PRPP levels are strictly age-dependent and substantially increased in the uremic erythrocytes. No definite alterations of enzyme halflifes of both enzymes could be discerned. No differences were found in the substrate saturation curves between the enzymes of normal and uremic erythrocytes. 3. Red cell methylene-blue stimulated pentose phosphate pathway (PPS) wasn't significantly lower in patients with chronic uremia than in controls, as could be shown by the determination of red cell ribose-5-phosphate concentration. There was no difference of the steady-state levels of ribose-5-phosphate in the age-dependent red cell fractions of both normal and uremic subjects. 4. The results support the assumption that the elevated ATP levels in the uremic red cells may be related to their higher intrinsic ATP synthetic capacity via salvage pathway. 5. The enzymatic alterations in the uremic red cells are independent of extracorpuscular factors including phosphate, and it was concluded that most of the described abnormalities in the uremic red cell metabolism reflect only the hypermetabolic state of a young red cell population. The conflicting results concerning red cell metabolism of uremic patients could be probably caused by an inconstant percentage of younger red cells in various uremic patients.