Abstract
To elucidate the possible role of acetylglutamate, known as the natural activator of ammonia-dependent carbamyl phosphate synthetase, in regulation of urea biosynthesis, studies were made on physiological factors affecting the hepatic acetylglutamate level as well as on the relationship between the level and the ureogenic capacity of mouse liver.
Examination of diurnal variation of the acetylglutamate level showed a sharp peak immediately after dietary feeding. During the other period of the day, the level remained low and relatively constant. It was found that the variation in the acetylglutamate level after meal is greatly affected by protein content of a given diet: the value changed from the minimum of 10 n moles/g liver to the maximum of over 200 n moles/g liver by varying the dietary casein content from 0 to 60 %, as far as examined.
The ureogenic capacity of the liver, as studied in vitro by using the tissue slices with NH4Cl as the substrate, also exhibited a marked variation after dietary feeding and was shown to have a direct and positive correlation with the acetylglutamate level in the original tissue.
These results provide the first unequivocal evidence that acetylglutamate functions as a limiting factor for the activity of carbamyl phosphate synthetase in vivo and plays a vital role in the metabolic control of urea synthesis.
Based on the previous information as to the regulatory property of acetylglutamate synthesizing enzyme of the hepatic mitochondria, it is assumable that the observed variation in the acetylglutamate level is due to a possible enhancement of the enzyme activity by increased supplies for the tissue of glutamate as the substrate and arginine as the activator upon dietary uptake of proteins.
