Purine synthesis de novo in cultured lymphoblast cells derived from patients with gout

Abstract

Rates of de novo purine synthesis in lymphoblast cell cultures derived from ten patients with gout were compared with those from control individuals. Since the growth rate of the culture, an assay procedure was developed to account for the variation in lymphoblast growth rates and to permit valid quantitative comparison between purine synthesis in each cell line. Clear differences were demonstrated between the rates of purine synthesis in cells from normal control subjects and those from patients with a deficiency of hypoxanthine-guanine phosphoribosyltransferase activity (HPRT-deficient). Lymphoblasts from the gouty patients showed purine synthesis either within the normal range or intermediate between this and the HPRT-deficient cells. In patients having normal renal function, de novo purine synthesis of lymphoblast cells correlated with the degree of urate production as reflected by the urinary excretion of urate over a 24 h period. Three patients, with demonstrable excessive production of urate in vivo, exhibited increased purine synthesis in lymphoblasts. This increased synthesis did not appear to result from any of the enzyme mutations currently recognized as responsible for abnormal purine metabolism.