Orotic acid-induced metabolic changes in the rat.

The effects of orotic acid consumption on hepatic lipid and nucleotide metabolism were examined concurrently in the rat. When orotic acid was fed at 1.0%, fatty liver development was evident by day 7 but not by day 3, whereas a decreased purine/pyrimidine ratio of hepatic acid-soluble nucleotides was noted by day 3. As nucleotide changes preceded hepatic fat accumulation, they could be a contributing factor in the etiology of fatty liver. When fed for 10 days, rats did not accumulate hepatic fat on a diet containing 0.1%, but did on 0.5 and 1.0%; similarly, the purine/pyrimidine ratio was not significantly affected on 0.1% but was decreased on both 0.5 and 1.0% orotic acid. These results indicate that orotic acid alters both hepatic lipid and nucleotides when consumed by rats at a level above 0.1%. As measured in these studies, hepatomegaly did not always accompany hepatic steatosis and appeared to be a subsequent development. In addition, L-dihydroorotate was shown to be as effective as orotic acid in increasing hepatic weight and lipid whereas uridine was ineffective.