Effects of orotic acid on purine and lipoprotein metabolism in man

In the present study, it was demonstrated that orotic acid, a normal intermediate in pyrimidine synthesis, inhibits purine biosynthesis de novo in normal man. This was associated with depletion of erythrocyte 5-phosphoribosyl-1-pyrophosphate (PP-ribose-P) content. Orotic acid had no inhibitory effect on purine biosynthesis in patients who exhibited elevated levels of PP-ribose-P due to a deficiency of hypoxanthine-guanine phosphoribosyltransferase. These findings suggest that the inhibitory effect of orotic acid on purine biosynthesis de novo is due to depletion of intracellular PP-ribose-P levels. This provides the first in vivo evidence that the physiologic intracellular concentration of PP-ribose-P is important for the regulation of purine biosynthesis de novo in man. Orotic acid administration also produced a modest though statistically significant decrease in the plasma concentration of cholesterol, triglycerides, and beta and prebeta lipoproteins. The uricosuric effect of orotic acid noted previously after its intravenous administration was confirmed in the present study in which the compound was administered orally.