ROLE OF N-ACETYLGLUTAMATE TURNOVER IN UREA SYNTHESIS BY RATS TREATED WITH THE THYROID-HORMONE

We determined whether the synthesis and degradation of N-acetylglutama te would regulate urea synthesis when the thyroid status was manipulat ed. Experiments were done on three groups of rats, each being given 6- propyl-2-thiouracil (PTU, a thyroid inhibitor) without a triiodothyron ine (T-3) treatment, treated with PTU + T-3, or receiving neither PTU nor T-3 (control). The plasma concentration and urinary excretion of u rea, the liver concentration of N-acetylglutamate, and the liver N-ace tylglutamate synthesis in rats given PTU alone were each significantly higher than in the control rats, Compared with the control rats, the liver N-acetylglutamate degradation was significantly lower in those r ats given PTU without the T-3 treatment. Treatment of the PTU-treated rats with T-3 reversed the effects of PTU to the values of the control rats, N-Acetylglutamate synthesis in the liver was closely correlated with the excretion of urea, and inverse correlation between the liver N-acetylglutamate degradation and urea excretion was found. These res ults suggest that the greater synthesis and lower degradation of N-ace tylglutamate in the hypothyroid (PTU alone) rats would be likely to in crease the hepatic concentration of this compound and stimulate urea s ynthesis.