Increased Activity of Adenine Phosphoribosyltransferase in Erythrocytes of Normal Newborn Infants

Abstract

ExtractTransient elevation of the activity of adenine phosphoribosyltransferase (APRT) was found along with hyperuricemia in an infant in the neonatal period. A systematic investigation was begun of the activity of the phosphoribosyltransferases in the first days of life. Adenine phosphoribosyltransferase and hypoxanthine guanine phosphoribosyltransferase (HGPRT) were assayed using radiochemical methods in which the nucleotide products of the enzymatic reactions are precipitated with lanthanum chloride. Phosphoribosyl pyrophosphate (PRPP) was assayed using a method based on the utilization of PRPP in a system containing (14C)adenine and APRT. The activity of APRT in the neonate was found to exceed consistently that of the adult. The degree of elevation was as great as that observed in patients with Lesch-Nyhan syndrome. The mean value of APRT in the adult was 665 nmol AMP/min/ml packed cells, whereas in the neonate the mean value was 1,150. The difference between neonate and adult was significant statistically at the <0.001 level.Erythrocytes of adults were fractionated into young and old cells. The activity of APRT in the young cells from each individual was 1.5-2.1 times that of the old cells. The concentrations of PRPP were significantly greater in the erythrocytes of neonates than in those of adults (P < 0.001). The mean concentration in the infants was 2.4 times the adult mean value.I t was concluded that the elevated activity of APRT in the neonate reflected partly a young population of cells and partly a stabilization by PRPP of APRT against the attrition of aging. SpeculationThe activity of APRT was first found to be elevated in the erythrocytes of patients with the Lesch-Nyhan syndrome. I t has been found to be elevated to an identical degree in patients with partial deficiency of H G P R T and with overproduction of uric acid without abnormality in HGPRT. Now it is apparent that APRT is elevated to precisely the same degree in the normal newborn infant. These observations speak , for a common mechanism of biologic control.

Developmental changes in purine phosphoribosyltransferases in human and rat tissues

“…The lower activity of hypoxanthine/guanine phosphoribosyltransferase in umbilical-cord blood is difficult to explain, but has also been reported by Durward & Boyle (1973). Increased adenine phosphoribosyltransferase activity in neonatal blood has been reported by Borden et al (1974), a finding that we have been unable to confirm. Many enzyme activities are altered in erythrocytes from cord blood (Jones & McCance, 1949) and may reflect the widespread physiological and metabolic changes at about the time of birth.…”

Pyrimidine Metabolism in Erythrocytes of the Newborn

“…A similar association of young cell age and high enzyme activity in erythrocytes has previously been reported for several enzymes of glucose metabolism (9) and purine metabolism (3,6). The specific activity of adenine phosphoribosyltransferase was positively correlated with the reticulocyte percentage (6).…”

“…The concentration of PRPP is signifi cantly higher in erythrocytes of neonates than in those of adults (3). OPRT and ODC in human hemolysate are stabilized in vitro by PRPP (16).…”

Comparison of human erythrocyte purine nucleotide metabolism and blood purine and pyrimidine degradation product concentrations before and after acute exercise in trained and sedentary subjects

“…A relationship between PRPP synthesis rate and purine nucleotide biosynthesis rate regulation has been demonstrated previously [ 11 , 30 , 31 ]. It has been observed that APRT activity increases together with an increase in PRPP concentration [ 32 , 33 ]. In human erythrocytes, PRPP concentration fluctuates around 1–5 µmol/L [ 11 ], just below the Km values of APRT and HGPRT (5–36 µmol/L) [ 31 ].…”