Metabolic fate of pyrimidines and purines in dietary nucleic acids ingested by mice

Abstract

1. In order to study the metabolism and tissue utilization of pyrimidines or purines ingested as dietary nucleic acid components, [14C]uracil, [14C]cytosine-labeled RNA, [14C]thymine-labeled DNA, or [14C]adenine-labeled RNA was fed to mice. 2. Absorption and catabolism of each ingested radioactive material were rapid; 80% or more of the ingested radioactivity was excreted as catabolic products over an 8-h period. 3. Utilization of the ingested radioactive materials for tissue synthesis of nucleic acids was limited under the usual conditions, the extent being 2--5%, 4 h after feeding. Such acid-insoluble radioactivity was localized principally in gastrointestinal tissue, and much lesser amounts, albeit significant, were found in the liver. 4. With increase in the dose of dietary nucleic acids, the amounts of utilized (nucleic acids and nucleotides) and utilizable (nucleosides and free bases) forms of uracil and cytosine and of adenine were increased in all tissues examined. Relationship between the dose and utilization together with additional findings support the view that gastrointestinal tissue and the liver utilize and degrade a greater part of the exogenous nucleic acid bases before their entry into the systemic circulation. 5. The metabolism of DNA thymine was unique in that it was significantly utilized for DNA synthesis in tissues other than the gastrointestinal tissue and liver to a comparative extent. The spleen was particularly active in this respect, and the hyperplastic, hematopoietic spleen was three times more active than the normal spleen. 6. Principal components of partially digested products in the intestinal lumen 1 h after the ingestion were uridine (33%) and cytidine (22%) in the case of [14C]uracil, [14C]cytosine-labeled RNA and inosine (53%) in the case of [14C]adenine-labeled RNA, in accordance with the view that purines and pyrimidines in nucleic acids are absorbed mainly in the form of nucleosides.