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Hepatic Nucleotide Levels and NAD-synthesis as Influenced by Dietary Orotic Acid and Adenine

National Institute of Arthritis and Metabolic Diseases, National Institutes of Health, Bethesda, Maryland

A simplified method is described for quantitating the effect of dietary orotic acid on the hepatic concentrations of adenine, guanine and uracil nucleotides in the rat. Within 16 hours after addition of 1% orotic acid to the diet, hepatic uracil nucleotide concentrations are 4 times normal, and concentrations of acid-soluble adenine, guanine and oxidized pyridine nucleotides have begun to decrease, coincident with a previously reported decrease in plasma lipid concentrations. Minimum values are observed after about 4 days. These effects of orotic acid are all rapidly reversed when 0.25% adenine sulfate is added to the diet. Addition of nicotinamide or nicotinic acid restores to normal only the depressed pyridine nucleotide concentration. Nicotinamide and nicotinic acid mononucleotide administered parenterally induce a 2- to 2.5-fold increase in hepatic oxidized pyridine nucleotide concentration of normal rats, but they have only slight effects in rats fed 1% orotic acid for 72 hours. The efficacy of nicotinamide in orotic acid-fed rats is improved by the administration of adenine. Depressed synthesis of pyridine nucleotides in rats fed orotic acid appears to reflect a relative unavailability of acid-soluble adenine nucleotides due either to an inhibition of purine synthesis de novo or increased competition for adenine by other metabolic pathways.