Role of Acetylglutamate in Ureotelism

Shigesada, Katsuya; Aoyagi, Kazumasa; Tatibana, Masamiti

doi:10.1111/j.1432-1033.1978.tb12250.x

Cited by 100 publications

(46 citation statements)

References 42 publications

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“…Shigesada et al (17) reported that the increase of N-acetylglutamate concentration under physiological conditions stimulated urea synthesis in isolated hepatocytes. The Ka value (0.11 mM) of the carbamylphosphate synthetase for the N-acetylglutamate was reported to be close to its physiological concentrations in mitochondria (14).…”

Section: Discussionmentioning

confidence: 99%

“…Variation in the N-acetylglutamate concentration has correlated well with urea synthesis in intact animals (14,17,27,28) and in isolated hepatocytes (12,29). Many investigators have indicated that a change in N-acetylglutamate synthesis was involved in regulating the liver concentration of N-acetylglutamate (17,26). N-Acetylglutamate synthetase (EC 2.3.1.1) has been shown to catalyze the acetylCoA-dependent acetylation of glutamate in liver mitochondria (16).…”

Section: Discussionmentioning

confidence: 99%

“…N-Acetylglutamate synthetase is activated by arginine (17,32). Therefore, we assumed the concentrations of liver glutamate and plasma arginine may have limited the N-acetylglutamate concentration.…”

Section: Discussionmentioning

confidence: 99%

“…Shigesada and Tatibana ( 16 ) have demonstrated that N -acetylglutamate synthetase (EC 2.3.1.1) catalyzed the acetylation of glutamate in the liver. This enzyme is specifically activated by arginine ( 17 ). On the other hand, Meijer et al ( 18 , 19 ) have suggested that there could be an alteration in the enzyme system catabolizing N -acetylglutamate in hepatic cytosol or in the system transporting this compound out of the mito-chondria under physiological conditions.…”

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Changes in N-Acetylglutamate Are Involved in Regulating Urea Synthesis in Rats Given a Low Gluten Diet Supplemented with L-Lysine, L-Methinone and L-Threonine

Tujioka

Tuchiya

Shi

et al. 2009

J Nutr Sci Vitaminol

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SummaryWe have shown that urinary urea excretion decreased in rats fed a low gluten diet supplemented with dietary limiting amino acids. The purpose of present study was to determine whether the addition of dietary limiting amino acids to a low gluten diet affected the synthesis and degradation of N -acetylglutamate and regulated urea synthesis. Experiments were done on two groups of rats, given diets containing 10% gluten or 10% gluten ϩ 0.5% L -lysine, 0.2% L -threonine and 0.2% L -methionine for 10 d. The urinary excretion of urea, and the liver concentration of N -acetylglutamate, and the liver activity of N -acetylglutamate synthetase decreased with the addition of dietary L -lysine, L -threonine and L -methionine. N -Acetylglutamate concentration in the liver was closely correlated with the N -acetylglutamate synthetase activity in the liver and excretion of urea. The greater degradation of N -acetylglutamate was observed in the group fed the 10% gluten ϩ L -lysine, L -threonine and L -methionine. The hepatic concentration of glutamate and plasma concentration of arginine were not related to the N -acetylglutamate concentration in the liver. These results suggest that the addition of limiting amino acids to the low gluten diet controls the synthesis and degradation of N -acetylglutamate in the liver and lowers urea synthesis. Key Words dietary limiting amino acids, urea synthesis, N -acetylglutamate synthesis, Nacetylglutamate degradation, rats Schimke ( 1 , 2 ) has suggested that the concentrations of urea-cycle intermediates were unchanged under conditions affecting the rate of urea excretion (e.g., ingestion of a high-protein diet) and concluded that the activities of various urea-cycle enzymes were regulatory factors of urea synthesis. However, many investigators have previously reported that there was an increase in urinary urea excretion without a comparable increase in the enzyme activities when a diet containing high quality protein was replaced by an isonitrogenous diet with low quality protein ( 3-6 ).We demonstrated that urinary excretion of urea increased with a 10% casein diet and still more with a 10% gluten diet as compared with a 10% whole egg protein diet ( 5 ). Gluten is known to be a lower quality protein than whole egg protein because of deficiency in lysine ( 7 ). The concentrations of threonine and sulfur amino acids in gluten are also lower than in whole egg protein. In a previous study ( 8 ), the activities of argininosuccinate synthetase and carbamylphosphate synthetase, urea cycle enzymes, were not affected by the dietary addition of L -lysine, L -threonine and L -methionine to a low gluten diet, while supplementation with these dietary limiting amino acids to a gluten diet decreased urea excretion.Substrate availability normally may limit the rate of urea synthesis ( 9 ). Urea formation has been shown to be stimulated by adding N -acetylglutamate in perfused liver ( 10-12 ) and in isolated hepatocytes ( 13 ) when substrates for urea production were present in excess. Thus, at lea...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Changes in N-Acetylglutamate Are Involved in Regulating Urea Synthesis in Rats Given a Low Gluten Diet Supplemented with L-Lysine, L-Methinone and L-Threonine

Tujioka

Tuchiya

Shi

et al. 2009

J Nutr Sci Vitaminol

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“…They were killed 8 h after the start of the feeding and acetylglutamate synthetase was purilied as described in the text [27], ammonia [19,20], intramitochondrial ATP/ ADP ratio [28] and Ca2+ [29], is a mediator which regulates urea biosynthesis in mammalian liver. The intramitochondrial level of acetylglutamate is regulated by the rate of its synthesis [3,7] and by the rate of the degradation [30]. Factors known to regulate the synthesis of acetylglutamate are the intracellular levels of arginine and glutamate [6] and the amount of acetylglutamate synthetase [9].…”

Section: ) Und O F J D Mice ( B )mentioning

confidence: 99%

Regulation of N‐Acetylglutamate Synthetase in Mouse Liver

Kawamoto

Ishida

Mori

et al. 1982

European Journal of Biochemistry

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N-Acetyl-L-glutamate synthetase catalyzes the synthesis of N-acetyl-L-glutamate, an allosteric and essential activator of carbamoyl-phosphate synthetase I in the liver of ureotelic animals. The enzyme is activated specifically by arginine.1. Mice were fed laboratory chow (protein content, 21 x) for 3 h and, after various times, N-acetyl-L-glutamate synthetase activity in the sonicated mitochondria was measured both in the presence and absence of 1 niM L-arginine. The activity in the absence of arginine did not significantly change after the feeding, while the activity in the presence of arginine increased with time and reached a maximum (fivefold increase) 9 h after the start of feeding, then decreased gradually. The ratio of the activity with arginine to that without arginine was 1.6 at the start of feeding and 5.5 at 9 h.2. Similar postprandial changes were observed with the mice on a protein-free diet, when these mice had previously been on a protein diet. No such change was seen with a protein-free diet when the mice were previously given a protein-free diet for a few days.3. Cycloheximide injection, which inhibited the total protein synthesis in the mouse liver by 90%, did not inhibit the postprandial increase in arginine activation of the synthetase. Thus, protein synthesis is presumably not required for the change.4. The enzymes with a low and a high arginine sensitivity were purified over tenfold from mitochondrial extracts of fasted and fed animals respectively. The extent of arginine activation of the enzymes remained unchanged, low or high, throughout the purification. In Sephacryl S-300 chromatography both types of the enzyme were eluted as a single peak and corresponded to a M, of 220000-250000. The change in arginine activation may be due to a modification of the enzyme molecule without a gross change in the molecular weight. 5. The diet-dependent change in sensitivity of the synthetase to arginine presents a new type of regulation of this enzyme and this regulation may contribute to the prevention of a rapid decrease in hepatic acetylglutamate levels after food ingestion N-Acetyl-L-glutamate is a specific and obligatory allosteric activator of mitochondrial carbamoyl-phosphate synthetase

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