Urea Cycle Function in the Dog with Emphasis on the Role of Arginine

Abstract

English Pointer puppies were used in experiments designed to assess urea cycle function. A preliminary assay revealed a dietary arginine (Arg) requirement of 0.40% for maximal weight gain of puppies fed a chemically defined L-amino acid diet. Subsequent studies showed that consumption of an Arg-free diet resulted in growth failure, emetic episodes, mild hyperammonemia, decreased plasma Arg and urea, and orotic aciduria. Oral administration of ornithine (Orn), equimolar to 0.40% Arg, failed to correct these Arg deficiency symptoms. Consumption of an equimolar concentration of citrulline (Cit), on the other hand, resulted in near normal weight gains, but blood and urine metabolite levels still did not parallel those of dogs fed Arg. Plasma glucose concentration was unaffected by dietary treatment. Older dogs (20 weeks of age) performed no better than younger dogs (7 weeks of age) when fed an Arg-free diet. In a serial bleeding study, plasma ammonia increased after ingestion of an Arg-free diet, reached a peak during emesis and declined immediately thereafter. In contrast, plasma ammonia of dogs fed an Arg-adequate diet remained relatively constant. It was apparent that in terms of meaningful Arg replacement value, Orn had minimal activity. Cit could replace Arg for growth, but was not as efficient as Arg for urea cycle function.