Role of <i>N</i>-Acetylglutamate Concentration and Ornithine Transport into Mitochondria in Urea Synthesis of Rats Given Proteins of Different Quality

Tujioka, Kazuyo; Lyou, Sunok; Hirano, Emi; Sano, Atushi; Hayase, Kazutoshi; Yoshida, A.; Yokogoshi, Hidehiko

doi:10.1021/jf025635r

Cited by 13 publications

(19 citation statements)

References 30 publications

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“…Therefore, the changes in N-acetylglutamate synthetase activity may have controlled N-acetylglutamate concentration and been one of the factors affecting urea synthesis in this study. The activities of various urea cycle enzymes were shown to depend on the quality of dietary protein (3)(4)(5)(6)8). However, the activity of N-acetylglutamate synthetase in the liver declined with the dietary addition of limiting amino acids in the present study.…”

Section: Discussioncontrasting

confidence: 58%

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: Discussioncontrasting

confidence: 58%

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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“…In the previous our study, the activities of arginase, carbamylphosphate synthetase and argininosuccinate synthetase, urea cycle enzymes, were proportional to the dietary protein quality, while urea excretion was greater in the group given the diet with low quality pro tein (5,6). The purpose of the present experiments was to elucidate the mechanism by which the dietary pro tein quality alters urea synthesis.…”

Section: Discussionmentioning

confidence: 68%

“…In our previous report (6), positive cor relations between the liver concentration of N-acetyl glutamate and urea excretion, and between the liver concentration and synthesis in vivo of N-acetylglu tamate were found when the dietary protein quality was manipulated. However, the plasma concentration of arginine was not correlated with urea excretion.…”

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confidence: 81%

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Role of N-Acetylglutamate Turnover in Urea Synthesis of Rats Given Proteins of Different Quality

Tujioka

Fukaya

Sano

et al. 2005

Journal of Nutritional Science and Vitaminology, J Nutr Sci Vit

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“…NAGS is expressed primarily in liver and small intestine and may have a key role as a regulator of ureagenesis by modulating the activity of CPSI through NAG [4,5]. Inherited NAGS deficiency appears to cause hyperammonemia due to secondary deficiency of CPSI deprived of its cofactor NAG [6].…”

Section: Introductionmentioning

confidence: 99%

Mammalian N-acetylglutamate synthase

Morizono

Caldovic

Shi

et al. 2004

Molecular Genetics and Metabolism

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N-Acetylglutamate synthase (NAGS, E.C. 2.3.1.1) is a mitochondrial enzyme that catalyzes the formation of N-acetylglutamate (NAG), an essential allosteric activator of carbamylphosphate synthetase I (CPSI). The mouse and human NAGS genes have been identified based on similarity to regions of NAGS from Neurospora crassa and cloned from liver cDNA libraries. These genes were shown to complement an argA-(NAGS) deficient Escherichia coli strain, and enzymatic activity of the proteins was confirmed by a new stable isotope dilution assay. The deduced amino acid sequence of mammalian NAGS contains a putative mitochondrial-targeting signal at the Nterminus. The mouse NAGS preprotein was overexpressed in insect cells to determine posttranslational modifications and two processed proteins with different N-terminal truncations have been identified. Sequence analysis using a hidden Markov model suggests that the vertebrate NAGS protein contains domains with a carbamate kinase fold and an acyl-CoA N-acyltransferase fold, and protein crystallization experiments are currently underway. Inherited NAGS deficiency results in hyperammonemia, presumably due to the loss of CPSI activity. We, and others, have recently identified mutations in families with neonatal and late-onset NAGS deficiency and the identification of the gene has now made carrier testing and prenatal diagnosis feasible. A structural analog of NAG, carbamylglutamate, has been shown to bind and activate CPSI, and several patients have been reported to respond favorably to this drug (Carbaglu®).

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Role of N-Acetylglutamate Concentration and Ornithine Transport into Mitochondria in Urea Synthesis of Rats Given Proteins of Different Quality

Cited by 13 publications

References 30 publications

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

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

Role of N-Acetylglutamate Turnover in Urea Synthesis of Rats Given Proteins of Different Quality

Mammalian N-acetylglutamate synthase

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