The rate of Purine Synthesis de nova in Blood Mononuclear Cells in vitro from Patients with Familial Hyperuricaemic Nephropathy

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Abstract
The rate of purine synthesis de novo in blood mononuclear cells in vitro and the activities of the purine salvage enzymes [hypoxanthine phosphoribosyltransferase (HPRT; EC 2.4.2.8), adenine phosphoribosyltransferase (APRT; EC 2.4.2.7) and ribosephosphate pyrophosphokinase (PP-ribose-P synthetase; EC 2.7.6.1)] and the concentration of phosphoribosylpyrophosphate (PP-ribose-P) were measured in the erythrocytes of affected family members. These subjects belong to families where hyperuricemia and renal failure occur together early in life, and the genetic transmission follows an autosomal dominant mode of inheritance. The authors term this syndrome, familial hyperuricemic nephropathy. No significant differences were detected in either the rates of purine synthesis de novo in vitro between the index patients and the control subjects with respect to the enzyme activities or the PP-ribose-P concentrations. Two groups of controls were used, healthy individuals and patients with a comparable degree of renal failure due to non-immune complex renal disease. Mononuclear cells from patients with Lesch-Nyhan syndrome (congenital HPRT deficiency) showed the expected acceleration of purine synthesis de novo in vitro. The accelerated purine synthesis de novo in vitro associated with phytohemagglutinin-induced lymphocyte transformation was detectable by the method used. Familial hyperuricemic nephropathy evidently is not due to a metabolic lesion which causes accelerated purine synthesis de novo. The primary abnormality may be a failure of the renal tubular net excretion of urate.

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