The Effect of Ammonia Administration on Orotic Acid Excretion in Rats

Ammonia fixation has been shown to proceed through at least three major pathways in ureotelic animals (1, 2). These are carbamyl phosphate synthetase, glutamic dehydrogenase, and glutamine synthetase. Perhaps the most significant means for removal of exogenous ammonia is by its conversion to urea (3). The initial step in this conversion is the production of carbamyl phosphate in the liver. Carbamyl phosphate, in addition to being a precursor for urea synthesis, is also believed to be a precursor for pyrimidine synthesis via the erotic acid pathway (2). Although erotic acid is not found in urine from normal humans or rats, its excretion has been observed in conditions of altered pyrimidine metabolism (4, 5). In the course of studies relating urinary organic acid excretion to acid-base balance, it was noted that an ultraviolet-absorbing acidic substance was rapidly excreted into the urine in large quantities after ammonium salt administration. Methods were devised to identify this substance. It was found to be erotic acid, and experiments were undertaken to determine some of the conditions under which it is excreted.