• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of biochemjBJ Latest papers and much more!
Biochem J. Jun 1, 2003; 372(Pt 2): 279–290.
PMCID: PMC1223426

N-acetylglutamate and its changing role through evolution.

Abstract

N -Acetylglutamate (NAG) fulfils distinct biological roles in lower and higher organisms. In prokaryotes, lower eukaryotes and plants it is the first intermediate in the biosynthesis of arginine, whereas in ureotelic (excreting nitrogen mostly in the form of urea) vertebrates, it is an essential allosteric cofactor for carbamyl phosphate synthetase I (CPSI), the first enzyme of the urea cycle. The pathway that leads from glutamate to arginine in lower organisms employs eight steps, starting with the acetylation of glutamate to form NAG. In these species, NAG can be produced by two enzymic reactions: one catalysed by NAG synthase (NAGS) and the other by ornithine acetyltransferase (OAT). In ureotelic species, NAG is produced exclusively by NAGS. In lower organisms, NAGS is feedback-inhibited by L-arginine, whereas mammalian NAGS activity is significantly enhanced by this amino acid. The NAGS genes of bacteria, fungi and mammals are more diverse than other arginine-biosynthesis and urea-cycle genes. The evolutionary relationship between the distinctly different roles of NAG and its metabolism in lower and higher organisms remains to be determined. In humans, inherited NAGS deficiency is an autosomal recessive disorder causing hyperammonaemia and a phenotype similar to CPSI deficiency. Several mutations have been recently identified in the NAGS genes of families affected with this disorder.

Full Text

The Full Text of this article is available as a PDF (640K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Vogel HJ. Path of Ornithine Synthesis in Escherichia Coli. Proc Natl Acad Sci U S A. 1953 Jul;39(7):578–583. [PMC free article] [PubMed]
  • VOGEL HJ, ABELSON PH, BOLTON ET. Short communications and preliminary notes on ornithine and proline synthesis in escherichia coli. Biochim Biophys Acta. 1953 Aug;11(4):584–585. [PubMed]
  • Maas WK, Novelli GD, Lipmann F. Acetylation of Glutamic Acid by Extracts of Escherichia Coli. Proc Natl Acad Sci U S A. 1953 Oct;39(10):1004–1008. [PMC free article] [PubMed]
  • ABELSON PH, BOLTON ET, ALDOUS E. Utilization of carbon dioxide in the synthesis of proteins by Escherichia coli. II. J Biol Chem. 1952 Sep;198(1):173–178. [PubMed]
  • VOGEL RH, VOGEL HJ. Acetylated intermediates of arginine synthesis in Bacillus subtilis. Biochim Biophys Acta. 1963 Jan 1;69:174–176. [PubMed]
  • GRISOLIA S, COHEN PP. Catalytic rôle of of glutamate derivatives in citrulline biosynthesis. J Biol Chem. 1953 Oct;204(2):753–757. [PubMed]
  • HALL LM, METZENBERG RL, COHEN PP. Isolation and characterization of a naturally occurring cofactor of carbamyl phosphate biosynthesis. J Biol Chem. 1958 Feb;230(2):1013–1021. [PubMed]
  • METZENBERG RL, MARSHALL M, COHEN PP. Purification of carbamyl phosphate synthetase from frog liver. J Biol Chem. 1958 Jul;233(1):102–105. [PubMed]
  • Cunin R, Glansdorff N, Piérard A, Stalon V. Biosynthesis and metabolism of arginine in bacteria. Microbiol Rev. 1986 Sep;50(3):314–352. [PMC free article] [PubMed]
  • Xu Y, Liang Z, Legrain C, Rüger HJ, Glansdorff N. Evolution of arginine biosynthesis in the bacterial domain: novel gene-enzyme relationships from psychrophilic Moritella strains (Vibrionaceae) and evolutionary significance of N-alpha-acetyl ornithinase. J Bacteriol. 2000 Mar;182(6):1609–1615. [PMC free article] [PubMed]
  • Harris BZ, Singer M. Identification and characterization of the Myxococcus xanthus argE gene. J Bacteriol. 1998 Dec;180(23):6412–6414. [PMC free article] [PubMed]
  • Abdelal AT, Nainan OV. Regulation of N-acetylglutamate synthesis in Salmonella typhimurium. J Bacteriol. 1979 Feb;137(2):1040–1042. [PMC free article] [PubMed]
  • VYAS S, MAAS WK. Feedback inhibition of acetylglutamate synthetase by arginine in Escherichia coli. Arch Biochem Biophys. 1963 Mar;100:542–546. [PubMed]
  • Haas D, Kurer V, Leisinger T. N-acetylglutamate synthetase of Pseudomonas aeruginosa. An assay in vitro and feedback inhibition by arginine. Eur J Biochem. 1972 Dec 4;31(2):290–295. [PubMed]
  • Hilger F, Culot M, Minet M, Pierard A, Grenson M, Wiame JM. Studies on the kinetics of the enzyme sequence mediating arginine synthesis in Saccharomyces cerevisiae. J Gen Microbiol. 1973 Mar;75(1):33–41. [PubMed]
  • Hoare DS, Hoare SL. Feedback regulation of arginine biosynthesis in blue-green algae and photosynthetic bacteria. J Bacteriol. 1966 Aug;92(2):375–379. [PMC free article] [PubMed]
  • Sakanyan V, Petrosyan P, Lecocq M, Boyen A, Legrain C, Demarez M, Hallet JN, Glansdorff N. Genes and enzymes of the acetyl cycle of arginine biosynthesis in Corynebacterium glutamicum: enzyme evolution in the early steps of the arginine pathway. Microbiology. 1996 Jan;142(Pt 1):99–108. [PubMed]
  • Wolf EC, Weiss RL. Acetylglutamate kinase. A mitochondrial feedback-sensitive enzyme of arginine biosynthesis in Neurospora crassa. J Biol Chem. 1980 Oct 10;255(19):9189–9195. [PubMed]
  • Wipe B, Leisinger T. Regulation of activity and synthesis of N-acetylglutamate synthase from Saccharomyces cerevisiae. J Bacteriol. 1979 Dec;140(3):874–880. [PMC free article] [PubMed]
  • Sakanyan V, Charlier D, Legrain C, Kochikyan A, Mett I, Piérard A, Glansdorff N. Primary structure, partial purification and regulation of key enzymes of the acetyl cycle of arginine biosynthesis in Bacillus stearothermophilus: dual function of ornithine acetyltransferase. J Gen Microbiol. 1993 Mar;139(3):393–402. [PubMed]
  • Martin PR, Mulks MH. Sequence analysis and complementation studies of the argJ gene encoding ornithine acetyltransferase from Neisseria gonorrhoeae. J Bacteriol. 1992 Apr;174(8):2694–2701. [PMC free article] [PubMed]
  • Marc F, Weigel P, Legrain C, Almeras Y, Santrot M, Glansdorff N, Sakanyan V. Characterization and kinetic mechanism of mono- and bifunctional ornithine acetyltransferases from thermophilic microorganisms. Eur J Biochem. 2000 Aug;267(16):5217–5226. [PubMed]
  • Crabeel M, Abadjieva A, Hilven P, Desimpelaere J, Soetens O. Characterization of the Saccharomyces cerevisiae ARG7 gene encoding ornithine acetyltransferase, an enzyme also endowed with acetylglutamate synthase activity. Eur J Biochem. 1997 Dec 1;250(2):232–241. [PubMed]
  • Cybis J, Davis RH. Organization and control in the arginine biosynthetic pathway of Neurospora. J Bacteriol. 1975 Jul;123(1):196–202. [PMC free article] [PubMed]
  • Jauniaux JC, Urrestarazu LA, Wiame JM. Arginine metabolism in Saccharomyces cerevisiae: subcellular localization of the enzymes. J Bacteriol. 1978 Mar;133(3):1096–1107. [PMC free article] [PubMed]
  • Morris CJ, Thompson JF. Acetyl coenzyme a-glutamate acetyltransferase and N-acetylornithine-glutamate acetyltransferase of chlorella. Plant Physiol. 1975 Jun;55(6):960–967. [PMC free article] [PubMed]
  • Davis RH. Compartmental and regulatory mechanisms in the arginine pathways of Neurospora crassa and Saccharomyces cerevisiae. Microbiol Rev. 1986 Sep;50(3):280–313. [PMC free article] [PubMed]
  • Morris CJ, Thompson JF, Johnson CM. Metabolism of Glutamic Acid and N-Acetylglutamic Acid in Leaf Discs and Cell-free Extracts of Higher Plants. Plant Physiol. 1969 Jul;44(7):1023–1026. [PMC free article] [PubMed]
  • Staub M, Dénes G. Mechanism of arginine biosynthesis in Chlamydomonas reinhardti. I. Purification and properties of ornithine acetyltransferase. Biochim Biophys Acta. 1966 Oct 17;128(1):82–91. [PubMed]
  • Yu YG, Turner GE, Weiss RL. Acetylglutamate synthase from Neurospora crassa: structure and regulation of expression. Mol Microbiol. 1996 Nov;22(3):545–554. [PubMed]
  • Abadjieva A, Pauwels K, Hilven P, Crabeel M. A new yeast metabolon involving at least the two first enzymes of arginine biosynthesis: acetylglutamate synthase activity requires complex formation with acetylglutamate kinase. J Biol Chem. 2001 Nov 16;276(46):42869–42880. [PubMed]
  • Hinde RW, Jacobson JA, Weiss RL, Davis RH. N-acetyl-L-glutamate synthase of Neurospora crassa. Characteristics, localization, regulation, and genetic control. J Biol Chem. 1986 May 5;261(13):5848–5852. [PubMed]
  • Haas D, Leisinger T. Multiple control of N-acetylglutamate synthetase from Pseudomonas aeruginosa: synergistic inhibition by acetylglutamate and polyamines. Biochem Biophys Res Commun. 1974 Sep 9;60(1):42–47. [PubMed]
  • Haas D, Leisinger T. In vitro assay and some properties of N-acetylglutamate synthetase from Escherichia coli. Pathol Microbiol (Basel) 1974;40(3):140–141. [PubMed]
  • Leisinger T, Haas D. N-Acetylglutamate synthase of Escherichia coli regulation of synthesis and activity by arginine. J Biol Chem. 1975 Mar 10;250(5):1690–1693. [PubMed]
  • Marvil DK, Leisinger T. N-acetylglutamate synthase of Escherichia coli: purification, characterization, and molecular properties. J Biol Chem. 1977 May 25;252(10):3295–3303. [PubMed]
  • Marc F, Weigel P, Legrain C, Glansdorff N, Sakanyan V. An invariant threonine is involved in self-catalyzed cleavage of the precursor protein for ornithine acetyltransferase. J Biol Chem. 2001 Jul 6;276(27):25404–25410. [PubMed]
  • Liu Y, Van Heeswijck R, Høj P, Hoogenraad N. Purification and characterization of ornithine acetyltransferase from Saccharomyces cerevisiae. Eur J Biochem. 1995 Mar 1;228(2):291–296. [PubMed]
  • Abadjieva A, Hilven P, Pauwels K, Crabeel M. The yeast ARG7 gene product is autoproteolyzed to two subunit peptides, yielding active ornithine acetyltransferase. J Biol Chem. 2000 Apr 14;275(15):11361–11367. [PubMed]
  • Gessert SF, Kim JH, Nargang FE, Weiss RL. A polyprotein precursor of two mitochondrial enzymes in Neurospora crassa. Gene structure and precursor processing. J Biol Chem. 1994 Mar 18;269(11):8189–8203. [PubMed]
  • Campbell JW. Arginine and urea biosynthesis in the land planarian: its significance in biochemical evolution. Nature. 1965 Dec 25;208(5017):1299–1301. [PubMed]
  • BISHOP SH, CAMPBELL JW. CARBAMYL PHOSPHATE SYNTHESIS IN THE EARTHWORM LUMBRICUS TERRESTRIS. Science. 1963 Dec 20;142(3599):1583–1585. [PubMed]
  • Horne FR. Urea metabolism in an estivating terrestrial snail Bulimulus dealbatus. Am J Physiol. 1973 Apr;224(4):781–787. [PubMed]
  • Speeg KV, Jr, Campbell JW. Arginine and urea metabolism in terrestrial snails. Am J Physiol. 1969 Apr;216(4):1003–1012. [PubMed]
  • Tramell PR, Campbell JW. Carbamyl phosphate synthesis in a land snail, Strophocheilus oblongus. J Biol Chem. 1970 Dec 25;245(24):6634–6641. [PubMed]
  • Mommsen TP, Walsh PJ. Evolution of urea synthesis in vertebrates: the piscine connection. Science. 1989 Jan 6;243(4887):72–75. [PubMed]
  • Mora J, Tarrab R, Martuscelli J, Soberón G. Characteristics of arginases from ureotelic and non-ureotelic animals. Biochem J. 1965 Sep;96(3):588–594. [PMC free article] [PubMed]
  • Palacios R, Tarrab R, Soberón G. Studies on the advent of ureotelism. Factors that render the hepatic arginase of the Mexican axolotl able to hydrolyse endogenous arginine. Biochem J. 1968 Dec;110(3):425–433. [PMC free article] [PubMed]
  • Mori M, Cohen PP. Preparation of crystalline carbamyl phosphate synthetase-I from frog liver. J Biol Chem. 1978 Nov 25;253(22):8337–8339. [PubMed]
  • Wixom RL, Reddy MK, Cohen PP. A concerted response of the enzymes of urea biosynthesis during thyroxine-induced metamorphosis of Rana catesbeiana. J Biol Chem. 1972 Jun 10;247(11):3684–3692. [PubMed]
  • Julsrud EA, Walsh PJ, Anderson PM. N-acetyl-L-glutamate and the urea cycle in gulf toadfish (Opsanus beta) and other fish. Arch Biochem Biophys. 1998 Feb 1;350(1):55–60. [PubMed]
  • Randall DJ, Wood CM, Perry SF, Bergman H, Maloiy GM, Mommsen TP, Wright PA. Urea excretion as a strategy for survival in a fish living in a very alkaline environment. Nature. 1989 Jan 12;337(6203):165–166. [PubMed]
  • Walsh P, Milligan C. Effects of feeding and confinement on nitrogen metabolism and excretion in the gulf toadfish Opsanus beta. J Exp Biol. 1995;198(Pt 7):1559–1566. [PubMed]
  • Korte JJ, Salo WL, Cabrera VM, Wright PA, Felskie AK, Anderson PM. Expression of carbamoyl-phosphate synthetase III mRNA during the early stages of development and in muscle of adult rainbow trout (Oncorhynchus mykiss). J Biol Chem. 1997 Mar 7;272(10):6270–6277. [PubMed]
  • Wright PA, Perry SF, Moon TW. Regulation of hepatic gluconeogenesis and glycogenolysis by catecholamines in rainbow trout during environmental hypoxia. J Exp Biol. 1989 Nov;147:169–188. [PubMed]
  • Anderson PM. Purification and properties of the glutamine- and N-acetyl-L-glutamate-dependent carbamoyl phosphate synthetase from liver of Squalus acanthias. J Biol Chem. 1981 Dec 10;256(23):12228–12238. [PubMed]
  • Anderson PM. Glutamine- and N-acetylglutamate-dependent carbamoyl phosphate synthetase in elasmobranchs. Science. 1980 Apr 18;208(4441):291–293. [PubMed]
  • Casey CA, Anderson PM. Submitochondrial localization of arginase and other enzymes associated with urea synthesis and nitrogen metabolism, in liver of Squalus acanthias. Comp Biochem Physiol B. 1985;82(2):307–315. [PubMed]
  • Casey CA, Anderson PM. Glutamine- and N-acetyl-L-glutamate-dependent carbamoyl phosphate synthetase from Micropterus salmoides. Purification, properties, and inhibition by glutamine analogs. J Biol Chem. 1983 Jul 25;258(14):8723–8732. [PubMed]
  • Meijer AJ, Lof C, Ramos IC, Verhoeven AJ. Control of ureogenesis. Eur J Biochem. 1985 Apr 1;148(1):189–196. [PubMed]
  • Caldovic Ljubica, Morizono Hiroki, Gracia Panglao Maria, Gallegos Rene, Yu Xiaolin, Shi Dashuang, Malamy Michael H, Allewell Norma M, Tuchman Mendel. Cloning and expression of the human N-acetylglutamate synthase gene. Biochem Biophys Res Commun. 2002 Dec 13;299(4):581–586. [PubMed]
  • Wu G, Morris SM., Jr Arginine metabolism: nitric oxide and beyond. Biochem J. 1998 Nov 15;336(Pt 1):1–17. [PMC free article] [PubMed]
  • Alonso E, Rubio V. Participation of ornithine aminotransferase in the synthesis and catabolism of ornithine in mice. Studies using gabaculine and arginine deprivation. Biochem J. 1989 Apr 1;259(1):131–138. [PMC free article] [PubMed]
  • Shigesada K, Tatibana M. Role of acetylglutamate in ureotelism. I. Occurrence and biosynthesis of acetylglutamate in mouse and rat tissues. J Biol Chem. 1971 Sep 25;246(18):5588–5595. [PubMed]
  • Guthöhrlein G, Knappe J. Structure and function of carbamoylphosphate synthase. I. Transitions between two catalytically inactive forms and the active form. Eur J Biochem. 1968 Dec;7(1):119–127. [PubMed]
  • Lusty CJ. Catalytically active monomer and dimer forms of rat liver carbamoyl-phosphate synthetase. Biochemistry. 1981 Jun 23;20(13):3665–3674. [PubMed]
  • Powers-Lee SG, Corina K. Domain structure of rat liver carbamoyl phosphate synthetase I. J Biol Chem. 1986 Nov 25;261(33):15349–15352. [PubMed]
  • Rodriguez-Aparicio LB, Guadalajara AM, Rubio V. Physical location of the site for N-acetyl-L-glutamate, the allosteric activator of carbamoyl phosphate synthetase, in the 20-kilodalton COOH-terminal domain. Biochemistry. 1989 Apr 4;28(7):3070–3074. [PubMed]
  • McCudden CR, Powers-Lee SG. Required allosteric effector site for N-acetylglutamate on carbamoyl-phosphate synthetase I. J Biol Chem. 1996 Jul 26;271(30):18285–18294. [PubMed]
  • Cheung CW, Raijman L. The regulation of carbamyl phosphate synthetase (ammonia) in rat liver mitochondria. Effects of acetylglutamate concentration and ATP translocation. J Biol Chem. 1980 Jun 10;255(11):5051–5057. [PubMed]
  • Lof C, Cohen M, Vermeulen LP, van Roermund CW, Wanders RJ, Meijer AJ. Properties of carbamoyl-phosphate synthetase (ammonia) in rat-liver mitochondria made permeable with toluene. Eur J Biochem. 1983 Sep 15;135(2):251–258. [PubMed]
  • Windmueller HG, Spaeth AE. Source and fate of circulating citrulline. Am J Physiol. 1981 Dec;241(6):E473–E480. [PubMed]
  • Alonso E, García-Pérez MA, Bueso J, Rubio V. N-acetyl-L-glutamate in brain: assay, levels, and regional and subcellular distribution. Neurochem Res. 1991 Jul;16(7):787–794. [PubMed]
  • Reichelt KL, Kvamme E. Acetylated and peptide bound glutamate and sapartate in brain. J Neurochem. 1967 Oct;14(10):987–995. [PubMed]
  • Meijer AJ, Van Woerkom GM. Turnover of N-acetylglutamate in isolated rat hepatocytes. Biochim Biophys Acta. 1982 Nov 17;721(3):240–246. [PubMed]
  • Shigesada K, Tatibana M. Enzymatic synthesis of acetylglutamate by mammalian liver preparations and its stimulation by arginine. Biochem Biophys Res Commun. 1971 Sep;44(5):1117–1124. [PubMed]
  • Reglero A, Rivas J, Mendelson J, Wallace R, Grisolia S. Deacylation and transacetylation of acetyl glutamate and acetyl ornithine in rat liver. FEBS Lett. 1977 Sep 1;81(1):13–17. [PubMed]
  • Kim S, Paik WK, Cohen PP. Ammonia intoxication in rats: protection by N-carbamoyl-L-glutamate plus L-arginine. Proc Natl Acad Sci U S A. 1972 Dec;69(12):3530–3533. [PMC free article] [PubMed]
  • Yamada E, Wakabayashi Y. Development of pyrroline-5-carboxylate synthase and N-acetylglutamate synthase and their changes in lactation and aging. Arch Biochem Biophys. 1991 Nov 15;291(1):15–23. [PubMed]
  • Bachmann C, Krähenbühl S, Colombo JP. Purification and properties of acetyl-CoA:L-glutamate N-acetyltransferase from human liver. Biochem J. 1982 Jul 1;205(1):123–127. [PMC free article] [PubMed]
  • Shigesada K, Tatibana M. N-Acetylglutamate synthetase from rat-liver mitochondria. Partial purification and catalytic properties. Eur J Biochem. 1978 Mar;84(1):285–291. [PubMed]
  • Sonoda T, Tatibana M. Purification of N-acetyl-L-glutamate synthetase from rat liver mitochondria and substrate and activator specificity of the enzyme. J Biol Chem. 1983 Aug 25;258(16):9839–9844. [PubMed]
  • Uchiyama C, Mori M, Tatibana M. Subcellular localization and properties of N-acetylglutamate synthase in rat small intestinal mucosa. J Biochem. 1981 Jun;89(6):1777–1786. [PubMed]
  • Kawamoto S, Sonoda T, Ohtake A, Tatibana M. Stimulatory effect of arginine on acetylglutamate synthesis in isolated mitochondria of mouse and rat liver. Biochem J. 1985 Dec 1;232(2):329–334. [PMC free article] [PubMed]
  • Caldovic Ljubica, Morizono Hiroki, Yu Xiaolin, Thompson Mark, Shi Dashuang, Gallegos Rene, Allewell Norma M, Malamy Michael H, Tuchman Mendel. Identification, cloning and expression of the mouse N-acetylglutamate synthase gene. Biochem J. 2002 Jun 15;364(Pt 3):825–831. [PMC free article] [PubMed]
  • Cheung CW, Raijman L. Arginine, mitochondrial arginase, and the control of carbamyl phosphate synthesis. Arch Biochem Biophys. 1981 Jul;209(2):643–649. [PubMed]
  • Kamemoto ES, Atkinson DE. Modulation of the activity of rat liver acetylglutamate synthase by pH and arginine concentration. Arch Biochem Biophys. 1985 Nov 15;243(1):100–107. [PubMed]
  • Coudé FX, Grimber G, Parvy P, Kamoun P. N-Acetyl glutamate synthetase in human liver: regulation of activity by L-arginine and N-acetylglutamate. Biochem Biophys Res Commun. 1981 Oct 15;102(3):1016–1020. [PubMed]
  • Wakabayashi Y, Iwashima A, Yamada E, Yamada R. Enzymological evidence for the indispensability of small intestine in the synthesis of arginine from glutamate. II. N-acetylglutamate synthase. Arch Biochem Biophys. 1991 Nov 15;291(1):9–14. [PubMed]
  • Saheki T, Ohkubo T, Katsunuma T. Regulation of urea synthesis in rat liver. Increase in the concentrations of ornithine and acetylglutamate in rat liver in response to urea synthesis stimulated by the injection of an ammonium salt. J Biochem. 1978 Dec;84(6):1423–1430. [PubMed]
  • Felipo V, Miñana MD, Grisolía S. Long-term ingestion of ammonium increases acetylglutamate and urea levels without affecting the amount of carbamoyl-phosphate synthase. Eur J Biochem. 1988 Oct 1;176(3):567–571. [PubMed]
  • McGivan JD, Chappell JB. On the metabolic function of glutamate dehydrogenase in rat liver. FEBS Lett. 1975 Mar 15;52(1):1–7. [PubMed]
  • Saheki T, Katsunuma T, Sase M. Regulation of urea synthesis in rat liver. Changes of ornithine and acetylglutamate concentrations in the livers of rats subjected to dietary transitions. J Biochem. 1977 Aug;82(2):551–558. [PubMed]
  • Saheki T, Katunuma N. Analysis of regulatory factors for urea synthesis by isolated perfused rat liver. I. Urea synthesis with ammonia and glutamine as nitrogen sources. J Biochem. 1975 Mar;77(3):659–669. [PubMed]
  • Shigesada K, Aoyagi K, Tatibana M. Role of acetylglutamate in ureotelism. Variations in acetylglutamate level and its possible significance in control of urea synthesis in mammalian liver. Eur J Biochem. 1978 Apr 17;85(2):385–391. [PubMed]
  • Stewart PM, Batshaw M, Valle D, Walser M. Effects of arginine-free meals on ureagenesis in cats. Am J Physiol. 1981 Oct;241(4):E310–E315. [PubMed]
  • Zollner H. Regulation of the n-acetylglutamate content of rat hepatocytes by the glutamate concentration. Adv Exp Med Biol. 1982;153:197–205. [PubMed]
  • Morimoto BH, Brady JF, Atkinson DE. Effect of level of dietary protein on arginine-stimulated citrulline synthesis. Correlation with mitochondrial N-acetylglutamate concentrations. Biochem J. 1990 Dec 15;272(3):671–675. [PMC free article] [PubMed]
  • Kawamoto S, Ishida H, Mori M, Tatibana M. Regulation of N-acetylglutamate synthetase in mouse liver. Postprandial changes in sensitivity to activation by arginine. Eur J Biochem. 1982 Apr;123(3):637–641. [PubMed]
  • Hayase K, Yoshida A. Role of ornithine in the N-acetylglutamate turnover in the liver of rats. Biosci Biotechnol Biochem. 1999 Mar;63(3):506–509. [PubMed]
  • Morita T, Mori M, Tatibana M. Regulation of N-acetyl-L-glutamate degradation in mammalian liver. J Biochem. 1982 Feb;91(2):563–569. [PubMed]
  • Palekar AG, Angadi CV. Effect of growth hormone on rat liver N-acetyl-L-glutamate. Arch Biochem Biophys. 1985 Mar;237(2):430–432. [PubMed]
  • Staddon JM, Bradford NM, McGivan JD. Effects of glucagon in vivo on the N-acetylglutamate, glutamate and glutamine contents of rat liver. Biochem J. 1984 Feb 1;217(3):855–857. [PMC free article] [PubMed]
  • Hayase K, Naganuma Y, Koie M, Yoshida A. Role of N-acetylglutamate turnover in urea synthesis by rats treated with the thyroid hormone. Biosci Biotechnol Biochem. 1998 Mar;62(3):535–539. [PubMed]
  • Hayase K, Yonekawa G, Yoshida A. Changes in liver concentration of N-acetylglutamate and ornithine are involved in regulating urea synthesis in rats treated with thyroid hormone. J Nutr. 1992 May;122(5):1143–1148. [PubMed]
  • Johnston JD, Brand MD. The mechanism of Ca2+ stimulation of citrulline and N-acetylglutamate synthesis by mitochondria. Biochim Biophys Acta. 1990 Jan 29;1033(1):85–90. [PubMed]
  • Lund P, Wiggins D. Is N-acetylglutamate a short-term regulator of urea synthesis? Biochem J. 1984 Mar 15;218(3):991–994. [PMC free article] [PubMed]
  • Van Dijk M, Lund P. N-Acetylglutamate in rat liver during foetal development. Biochem J. 1984 Sep 15;222(3):837–838. [PMC free article] [PubMed]
  • Meijer AJ, Verhoeven AJ. N-acetylglutamate and urea synthesis. Biochem J. 1984 Oct 15;223(2):559–560. [PMC free article] [PubMed]
  • Meijer AJ, Lamers WH, Chamuleau RA. Nitrogen metabolism and ornithine cycle function. Physiol Rev. 1990 Jul;70(3):701–748. [PubMed]
  • Stewart PM, Walser M. Short term regulation of ureagenesis. J Biol Chem. 1980 Jun 10;255(11):5270–5280. [PubMed]
  • Coude FX, Grimber G. Inhibition of urea synthesis by pent-4-enoic acid: potentiation by ammonia. Biochem Biophys Res Commun. 1984 Jan 13;118(1):47–52. [PubMed]
  • Aoyagi K, Mori M, Tatibana M. Inhibition of urea synthesis by pent-4-enoate associated with decrease in N-acetyl-L-glutamate concentration in isolated rat hepatocytes. Biochim Biophys Acta. 1979 Nov 1;587(4):515–521. [PubMed]
  • Coude FX, Sweetman L, Nyhan WL. Inhibition by propionyl-coenzyme A of N-acetylglutamate synthetase in rat liver mitochondria. A possible explanation for hyperammonemia in propionic and methylmalonic acidemia. J Clin Invest. 1979 Dec;64(6):1544–1551. [PMC free article] [PubMed]
  • Wolf B, Hsia YE, Tanaka K, Rosenberg LE. Correlation between serum propionate and blood ammonia concentrations in propionic acidemia. J Pediatr. 1978 Sep;93(3):471–473. [PubMed]
  • Landers PJ. Therapieplan für die diabetische Ketoazidose. Med Welt. 1972 Feb 26;9:298–300. [PubMed]
  • Coudé FX, Grimber G, Parvy P, Pham Dinh D, Bardet J, Saudubray JM. Characterization of enzymatic deficiencies of branched chain amino-acid catabolism in human fibroblasts by genetic complementation. Biochem Biophys Res Commun. 1983 Jul 18;114(1):175–182. [PubMed]
  • Williams CA, Tiefenbach S, McReynolds JW. Valproic acid-induced hyperammonemia in mentally retarded adults. Neurology. 1984 Apr;34(4):550–553. [PubMed]
  • Coude FX, Grimber G, Parvy P, Rabier D, Petit F. Inhibition of ureagenesis by valproate in rat hepatocytes. Role of N-acetylglutamate and acetyl-CoA. Biochem J. 1983 Oct 15;216(1):233–236. [PMC free article] [PubMed]
  • Coudé FX, Rabier D, Cathelineau L, Grimber G, Parvy P, Kamoun P. A mechanism for valproate-induced hyperammonemia. Adv Exp Med Biol. 1982;153:153–161. [PubMed]
  • Trost LC, Lemasters JJ. The mitochondrial permeability transition: a new pathophysiological mechanism for Reye's syndrome and toxic liver injury. J Pharmacol Exp Ther. 1996 Sep;278(3):1000–1005. [PubMed]
  • Bachmann C, Brandis M, Weissenbarth-Riedel E, Burghard R, Colombo JP. N-acetylglutamate synthetase deficiency, a second patient. J Inherit Metab Dis. 1988;11(2):191–193. [PubMed]
  • Bachmann C, Colombo JP, Jaggi K. N-acetylglutamate synthetase (NAGS) deficiency: diagnosis, clinical observations and treatment. Adv Exp Med Biol. 1982;153:39–45. [PubMed]
  • Bachmann C, Krähenbühl S, Colombo JP, Schubiger G, Jaggi KH, Tönz O. N-acetylglutamate synthetase deficiency: a disorder of ammonia detoxication. N Engl J Med. 1981 Feb 26;304(9):543–543. [PubMed]
  • Burlina AB, Bachmann C, Wermuth B, Bordugo A, Ferrari V, Colombo JP, Zacchello F. Partial N-acetylglutamate synthetase deficiency: a new case with uncontrollable movement disorders. J Inherit Metab Dis. 1992;15(3):395–398. [PubMed]
  • Elpeleg ON, Colombo JP, Amir N, Bachmann C, Hurvitz H. Late-onset form of partial N-acetylglutamate synthetase deficiency. Eur J Pediatr. 1990 Jun;149(9):634–636. [PubMed]
  • Forget PP, van Oosterhout M, Bakker JA, Wermuth B, Vles JS, Spaapen LJ. Partial N-acetyl-glutamate synthetase deficiency masquerading as a valproic acid-induced Reye-like syndrome. Acta Paediatr. 1999 Dec;88(12):1409–1411. [PubMed]
  • Guffon N, Vianey-Saban C, Bourgeois J, Rabier D, Colombo JP, Guibaud P. A new neonatal case of N-acetylglutamate synthase deficiency treated by carbamylglutamate. J Inherit Metab Dis. 1995;18(1):61–65. [PubMed]
  • Hinnie J, Colombo JP, Wermuth B, Dryburgh FJ. N-Acetylglutamate synthetase deficiency responding to carbamylglutamate. J Inherit Metab Dis. 1997 Nov;20(6):839–840. [PubMed]
  • Morris AA, Richmond SW, Oddie SJ, Pourfarzam M, Worthington V, Leonard JV. N-acetylglutamate synthetase deficiency: favourable experience with carbamylglutamate. J Inherit Metab Dis. 1998 Dec;21(8):867–868. [PubMed]
  • Pandya AL, Koch R, Hommes FA, Williams JC. N-acetylglutamate synthetase deficiency: clinical and laboratory observations. J Inherit Metab Dis. 1991;14(5):685–690. [PubMed]
  • Plecko B, Erwa W, Wermuth B. Partial N-acetylglutamate synthetase deficiency in a 13-year-old girl: diagnosis and response to treatment with N-carbamylglutamate. Eur J Pediatr. 1998 Dec;157(12):996–998. [PubMed]
  • Schubiger G, Bachmann C, Barben P, Colombo JP, Tönz O, Schüpbach D. N-acetylglutamate synthetase deficiency: diagnosis, management and follow-up of a rare disorder of ammonia detoxication. Eur J Pediatr. 1991 Mar;150(5):353–356. [PubMed]
  • Vockley J, Vockley CM, Lin SP, Tuchman M, Wu TC, Lin CY, Seashore MR. Normal N-acetylglutamate concentration measured in liver from a new patient with N-acetylglutamate synthetase deficiency: physiologic and biochemical implications. Biochem Med Metab Biol. 1992 Feb;47(1):38–46. [PubMed]
  • Elpeleg Orly, Shaag Avraham, Ben-Shalom Efrat, Schmid Tal, Bachmann Claude. N-acetylglutamate synthase deficiency and the treatment of hyperammonemic encephalopathy. Ann Neurol. 2002 Dec;52(6):845–849. [PubMed]
  • Caldovic Ljubica, Morizono Hiroki, Panglao Maria Gracia, Cheng Sabrina F, Packman Seymour, Tuchman Mendel. Null mutations in the N-acetylglutamate synthase gene associated with acute neonatal disease and hyperammonemia. Hum Genet. 2003 Apr;112(4):364–368. [PubMed]
  • Rubio V, Grisolía S. Treating urea cycle defects. Nature. 1981 Aug 6;292(5823):496–496. [PubMed]
  • O'Connor JE, Jordá A, Grisolía S. Acute and chronic effects of carbamyl glutamate on blood urea and ammonia. Eur J Pediatr. 1985 Jan;143(3):196–197. [PubMed]
  • Grau E, Felipo V, Miñana MD, Grisolía S. Treatment of hyperammonemia with carbamylglutamate in rats. Hepatology. 1992 Mar;15(3):446–448. [PubMed]
  • Lee J. A decrease in ammonia content in portal blood of rabbits administered with ginseng powder. Nihon Juigaku Zasshi. 1978 Dec;40(6):729–731. [PubMed]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • Compound
    Compound
    PubChem Compound links
  • Conserved Domains
    Conserved Domains
    Link to related CDD entry
  • MedGen
    MedGen
    Related information in MedGen
  • Pathways + GO
    Pathways + GO
    Pathways, annotations and biological systems (BioSystems) that cite the current article.
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...