A survey of the metabolism of orotic acid in the rat.

Orotic acid has been demonstrated to be an effective precursor of the nucleic acid pyrimidines in animal tissues, both in viva (1, 2) and in vitro (3,4). It is a growth-stimulating factor for certain pyrimidineless mutants of microorganisms (5-8) and may be partially replaced by oxalacetic acid (9) or ureidosuccinic acid (10, 11) in some strains. The possibility that erotic acid, and, hence, the synthesis of nucleic acids, may be metabolically related to the intermediates in the Krebs oxidative cycle is under investigation in this laboratory. This paper presents the results of a preliminary survey of the metabolic pathways followed by erotic acid in the rat. Labeled erotic acid (4-carboxyuracil-6-C14) has been prepared (12) and the distribution of the radioactivity has been determined at various times (2 hours to 4 days) following a single intraperitoneal dose of the erotic acid. Attention has been given to the ‘over-all distribution of radioactivity in liver cell fractions, respiratory carbon dioxide, urine, and feces; in addition, the localization of the radioactivity in the nucleic acids and pyrimidine nucleotides of the liver, transplanted tumors, and internal organs has been determined.