Regulation of Urea Synthesis in Rat Liver

Changes of Ornithine and Acetylglutamate Concentrations in the Livers of Rats Subjected to Dietary Transitions

Abstract

Regulation of urea synthesis in vivo was studied in rats subjected to acute dietary transitions from 70% to 5% casein diet or vice versa.
Significant increase/decrease of urea excretion and urea in the liver preceded increase/decrease of argininosuccinate synthetase [EC 6. 3. 4. 5] activity during the dietary transitions.
Immunochemical determination of argininosuccinate synthetase showed that the increase/ decrease of the enzyme activity is directly related to the actual increase/decrease of the amount of enzyme protein.
The ratios of the initial velocity of urea synthesis from ammonium chloride to the enzymatic activity of argininosuccinate synthetase in the perfused livers were determined. Shortly after the switch of casein diet from 70% to 5%, the ratios decreased to much lower values than those of rats fed on the 5% casein diet for 7 days, while, during the acute transition from 5% to 70% casein diet, the ratios increased above the values of rats fed on the 70% casein diet for 7 days.
The concentrations of ornithine and acetylglutamate capable of stimulating urea synthesis changed significantly shortly after the dietary switch. In particular, the concentration of ornithine overshot the steady-state level of rats fed on 70% casein after the dietary switch from 5% to 70% casein. Ornithine concentration declined rapidly after the dietary switch from 70% to 5%, falling below the steady-state level of rats fed on the 5% casein diet. Thus, in both cases, new steady-state levels of ornithine concentration were established. The findings that fluctuations of ornithine and acetylglutamate concentration were greater and occurred prior to the activity changes of argininosuccinate synthetase strongly suggested a possible regulatory function of these amino acids in urea synthesis.