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Effect of Arginine-Free Diet on Ammonia Metabolism in Young and Adult Ferrets^1,2,

Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, MI 48109-0244

Two-month-old, male ferrets were fasted for 16 h and fed a synthetic, arginine-free diet. Within 2–3 h after ingesting the diet, they developed hyperammonemia and encephalopathy. Ammonia levels in the serum, brain and cerebrospinal fluid were greatly elevated compared to those of ferrets fed the synthetic diet supplemented with arginine. Orotic acid and glucose levels in serum were also significantly elevated. Urinary orotic acid was significantly increased but citrate and creatinine level were unaltered. Adult (18-mo-old) ferrets did not develop hyperammonemia and encephalopathy after eating the arginine-free diet. Serum and urinary orotic acid levels were significantly elevated in the adult ferrets fed arginine-free diet. Hyperammonemia and encephalopathy were prevented in young ferrets by supplying dietary arginine and abbreviated by ornithine injections given during encephalopathy. These results suggest that young ferrets are unable to meet their ornithine needs from precursors other than arginine, whereas adult ferrets appear to be able to synthesize ornithine from sources other than dietary arginine. Intraperitoneal injection of sodium benzoate to young ferrets fed arginine-free diet failed to decrease serum ammonia levels.

KEY WORDS: • arginine deficiency • ammonia • orotic acid • ferret • sodium benzoate

¹ This work was supported by a grant AI 20236-02 from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD. D. R. Deshmukh is a recipient of a research career development award from the National Institutes of Health.

² This work was presented, in part, at the annual meeting of the Federation of American Societies for Experimental Biology, Anaheim, CA, April 1985.

³ Present address: Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109-0244.

⁴ Address for correspondence: F7828, Box 66, C. S. Mott Children's Hospital, University of Michigan, Ann Arbor, MI 48109-0244.

Manuscript received 22 February 1985. Revision accepted 27 November 1985.