Adenine-induced orotic aciduria in rats fed diets with and without orotic acid

Abstract

Diets with 0, 0.05, 0.25, and 1% adenine sulfate, each with and without 1% orotic acid, were fed for 10 days to female weanling rats, 5 animals per treatment. In the absence of dietary orotic acid, urinary excretion of orotic acid was increased 8-fold (0.09 to 0.73 mg/day) by 0.25% adenine sulfate. In the presence of dietary orotic acid, excretion was 50 times greater and was enhanced 3-fold (4.4 to 12.7 mg/day) by 0.25% adenine sulfate. Adenine sulfate at 0.05% was ineffective at stimulating orotic acid excretion; adenine sulfate at 1.0% was as effective as 0.25% but led to symptoms of adenine toxicity. The two high levels of adenine also prevented development of fatty livers induced by orotic acid. Thus, the prevention of such fatty livers is associated with increased excretion of orotic acid. The orotic aciduria could be due to competition for renal reabsorption by adenine metabolites but more likely results from competition between pyrimidine and purine metabolism in the liver.