Species Specificity in the Metabolic Consequences of Orotic Acid Consumption

Metabolic consequences of orotic acid composition were examined in several mammalian species. In contrast to rats which respond to orotic acid consumption with increases in hepatic weight and lipid content, mice, guinea pigs, hamsters, pigs and monkeys did not so respond. An increase in hepatic weight was noted in pigs although it was not accompanied by a fatty liver. To assess the basis for the species specificity, the fate of orally administered [6-14C]orotic acid was compared in rats and mice. During the first 6 hours mice absorbed more than rats but accumulated less of the dose in liver and excreted much more in urine. The large difference between the two species in urinary excretion was confirmed in an experiment employing 1.0% unlabeled dietary orotic acid. These metabolic differences may contribute to the lack of hepatic changes in mice in response to orotic acid. As changes in purine and pyrimidine levels in the hepatic acid-soluble nucleotide pool may be responsible for the aberrant lipid metabolism noted after orotic acid ingestion, these changes were compared in rats and mice. Rats exhibited a larger decrease in the purine to pyrimidine ratio than did mice; even after orotic acid treatment, the ratio in mice did not differ significantly from that in control rats. These findings may also help explain the lack of fatty liver formation in mice.