Citric, orotic, and other organic acids in rats injected with active or inactive urease

Male rats were fed laboratory chow or a purified L-amino acid diet containing 11.2 or 5.6 g arginine/kg. Hyperammonemia was produced by injection of crystalline jackbean urease. Control animals were injected with saline or inactivated urease. Rats injected with 55 U urease activity/kg body wt (an LD50 dose) exhibited acute signs of hyperammonemia and elevated orotate and citrate in their urine. Plasma glucose, lactate, citrate, and alpha-ketoglutarate concentrations were also markedly elevated. Three injections of active urease (10 U/kg body wt) given at intervals of about 10 h produced hyperammonemia, which persisted for 25 h after the first injection. Blood glucose and ammonia concentrations were increased 2.6- and 22-fold, respectively, when compared with controls. Total urinary citrate excretion for 25 h was 371 mueq for active urease-injected rats compared with 62 mueq for rats injected with inactivated urease. Rats fed a purified amino acid diet containing 5.6 g arginine/kg excreted greater quantities of urea, citrate, and orotic acid than rats fed 11.2 g arginine/kg of diet. Injection of active urease increased citrate excretion by rats fed either concentration of dietary arginine. Changes produced with active urease were not observed if inactivated urease was injected.