Regulation of Urea Synthesis in Rat Liver

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Abstract
1. Intraperitoneal injection of ammonium chloride or ammonium bicarbonate, 2 mmol/kg body weight, caused an increase in the concentrations of ammonia (maximum at 5 min) and urea (maximum at 10 min) in the livers of rats fed on laboratory chow. 2. The increase in the concentration of urea was accompanied by about 200%, 100%, and 40% increases in the concentrations of acetylglutamate, ornithine, and citrulline, respectively. 3. Overnight starvation before ammonium chloride injection did not affect the results. 4. In the livers of rats fed on a high protein diet, the ornithine level was increased to a similar extent in response to ammonium salt injection but that of acetylglutamate was not, and the concentrations of these amino acids and urea remained at the highest levels. 5. In the livers of rats fed on a low protein diet, the concentration of urea did not change until 5 min after the injection and then increased gradually. The sum of the concentrations of ornithine and citrulline did not change significantly until 10 min, while the concentration of acetylglutamate increased more quickly (maximum at 10 min). 6. In perfused liver, the addition of ammonium salt to the perfusate caused an increase in the concentrations of acetylglutamate and citrulline as observed in vivo, while the concentration of ornithine, one-fifth of that in vivo, did not respond to the addition. From these results, we conclude that ammonia, a direct substrate for urea synthesis, may control the concentrations of both ornithine and acetylglutamate in the liver, directly or indirectly.

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