Arginine affects urea synthesis in rats treated with thyroid hormone.

The purpose of the present study was to determine whether the regulation of urea synthesis was mediated through the activation of N-acetylglutamate synthesis by arginine and whether the concentration of glutamate or activity of N-acetylglutamate synthetase might control N-acetylglutamate concentration when the thyroid status was manipulated. Three groups of rats were given 6-propyl-2-thiouracil (PTU, thyroid inhibitor) without triiodothyronine (T3) treatment, treated with PTU + T3 or treated with neither PTU nor T3 (control). Urinary excretion of urea, liver concentration of N-acetylglutamate and plasma concentration of arginine in rats given PTU + T3 were significantly lower than in rats given PTU alone. Liver concentration of N-acetyl-glutamate was correlated with plasma concentration of arginine (r = 0.842, P < 0.001). The activity of N-acetylglutamate synthetase and glutamate concentration in liver of the PTU + T3-treated group were significantly higher than in the group treated with PTU alone. Arginine administration (0.5 mmol/100 g body wt) elevated the liver concentration of N-acetylglutamate in all three groups. The results suggest that the greater concentration of arginine in the hypothyroid (PTU alone) rats is likely to increase the N-acetylglutamate concentration and stimulate urea synthesis.