Alterations in liver nucleic acids and nucleotides in arginine deficient rats

Dietary arginine deficiency is associated with retarded growth and depressed feed intake. Nucleic acid biosynthesis as indicated by the incorporation of [6-¹⁴C]-orotic acid and [³²p]-orthophosphate was significantly depressed in rats fed an arginine deficient diet. The activities of the pyrimidine enzymes, aspartate transcarbamylase (ATC) and dihydroorotate dehydrogenase (DHODH) were significantly increased in rats fed an arginine deficient diet. ATC and DHODH activities in rats fed the arginine deficient diet returned to control activities after 3 wk of feeding. Orotidine 5′ phosphate decarboxylase and orotate phosphoribosyl transferase activities were not affected by dietary arginine availability. In the rat fed an arginine deficient diet there was an increase in total liver pyrimidine nucleotides and a decrease in the total purine nucleotides. Significant alterations in the individual liver nucleotides were also observed. Incubation of various tissues obtained from rats fed an arginine deficient diet or a complete diet with glutamine (5mM) revealed that the liver is the major site of orotic acid synthesis. Orotic acid production in liver slices using glutamine as the nitrogen source was significantly greater in rats fed an arginine deficient diet compared to controls. The orotic aciduria occurring in rats fed an arginine deficient diet is associated with increased synthesis and decreased utilization of pyrimidines.