Orotic Aciduria and Increased Nitrogen Catabolism in Rats

Abstract

In vitro incorporation of [14C] bicarbonate into orotic acid by rat liver slices was used to study the rate of orotic acid (OA) biosynthesis in the presence of physiological (0.73 mM) and saturation concentrations (5 mM) of NH4Cl. The influence of body size on OA synthesis in rats fed purified L-amino acid diets with (C) or without (-Arg) was examined. OA biosynthesis was significantly greater at both NH4Cl concentrations examined in liver slices obtained from -Arg rats for all sizes of rats. A linear decrease (r = 0.92) in OA synthesis as a function of body size was observed for rats fed either of the diets. The rate of OA biosynthesis was also found to increase linearly (r = 0.98) in livers from rats fed increasing dietary protein when determined by incubation with physiological concentrations of NH4Cl. OA biosynthesis was also found to increase with increase in length of fasting. Alteration in urinary OA and urea confirm these rates of synthesis. These results support the hypothesis that when the urea cycle is overtaxed, carbamyl phosphate (CP) synthesized intramitochondrially by CP synthetase I may be shunted into pyrimidine biosynthesis.