Enzyme Regulation of N-Acetylglutamate Synthesis in Mouse and Rat Liver
Ṉ-Acetylglutamate (AGA) synthetase of mammalian liver is known to be stimulated by low concentrations of arginine. The arginine sensitivity of the synthetase was found to show postprandial changes in the liver of DD-Y mice. AGA synthetase activity assayed in the absence of arginine changed only slightly during and after the feeding. With 1 mM arginine, the activity increased and reached a peak value 9 h after the start of feeding. The activation ratios were about 2 and 6 at 0 and 9 h, respectively. Similar changes occurred with 0%, 20%, and 60% casein diets. When the enzymes were partially purified, the respective activation ratios remained the same, suggesting no involvement of a readily dissociable low molecular weight compound. Treatment of mice with cycloheximide did not abolish the increase in the activation ratio. A homogeneous preparation of the synthetase was obtained by a 30,000-fold purification from sonicated mitoplasts of rat liver mitochondria. The molecular weight was 160,000, as estimated on sucrose density gradient centrifugation, with subunits of 57,000 on SDS-gel electrophoresis. The enzyme had a hydrophobic nature, was stabilized by Triton X-100, and contained little phospholipid. Although the molecular basis of the increase in the activation ratio remains to be established, the modification of the nature of AGA synthetase introduces another aspect into the elaborate regulation of urea synthesis.
KeywordsPhosphorus Urea Arginine Leucine Acetyl
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