Dietary feedback regulation of purine and pyrimidine biosynthesis in man

Ten days after a healthy person has consumed a purine-free isoenergetic diet, the excretion of (endogenous) uric acid reaches a minimum and remains constant thereafter. Purines are absorbed in different degrees from various biochemical sources added to such a diet--little from DNA, nearly all from ribomononucleotides--presumably owing to different rates of hydrolysis. There is always a linear relationship between dietary purine content and uric acid excretion, independent of the source of purine. The findings suggest that dietary purines play a minor role (if any) in the regulation of purine synthesis, contrary to the conclusions of other workers. The demonstration that oral administration of uridine diminishes the oroticaciduria in patients with hereditary oroticaciduria suggested dietary feedback regulation of pyrimidine biosynthesis by pyrimidine nucleosides in the diet. The reduction of allopurinol-induced oroticaciduria by dietary RNA pointed in the same direction. Closer analysis with RNA hydrolysate and isolated purine as well as pyrimidine nucleotides, however, revealed that not only pyrimidine derivatives but also purine mononucleotides diminish oroticaciduria. The nucleotides had no influence on the change in the activity of orotidine-5'-phosphate decarboxylase (EC 4.1.1.23), induced by allopurinol; this makes an effect on the decarboxylase unlikely. The feedback regulation is assumed to act by inhibition of an earlier step.