Wikipedia:WikiProject Chemicals/Chembox validation/VerifiedDataSandbox and N-Acetylglutamic acid: Difference between pages

{{DISPLAYTITLE:''N''-Acetylglutamic acid}}

{{chembox

| Verifiedfields = changed

| Watchedfields = changed

| verifiedrevid = 462256958

| Name = ''N''-Acetylglutamic acid

| ImageFile = N-Acetylglutamic acid.png

| ImageFile_Ref = {{chemboximage|correct|??}}

| ImageSize = 160

| ImageName = Skeletal formula of ''N''-acetylglutamic acid

| IUPACName = 2-Acetamidopentanedioic acid<ref>{{cite web|title=''N''-Acetyl-<small>DL</small>-glutamic acid - Compound Summary|url=https://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=185|work=PubChem Compound|publisher=National Center for Biotechnology Information|access-date=25 June 2012|location=USA|date=25 March 2005|at=Identification}}</ref>

| OtherNames = Acetylglutamic acid{{citation needed|date=June 2012}}

|Section1={{Chembox Identifiers

| Abbreviations = {{unbulleted list|''N''-Acetyl-Glu{{citation needed|date=June 2012}}|NAcGlu{{citation needed|date=June 2012}}|Ac-Glu-OH{{citation needed|date=June 2012}}

}}

| CASNo = 5817-08-3

| CASNo_Ref = {{cascite|changed|??}}

| CASNo1 = 19146-55-5

| CASNo1_Ref = {{cascite|changed|??}}

| CASNo1_Comment = <small>''R''</small>

| CASNo2 = 1188-37-0

| CASNo2_Ref = {{cascite|correct|CAS}}

| CASNo2_Comment = <small>''S''</small>

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = MA61H539YZ

| UNII_Comment = <small>''S''</small>

| PubChem = 185

| PubChem1 = 1560015

| PubChem1_Comment = <small>''R''</small>

| PubChem2 = 70914

| PubChem2_Comment = <small>''S''</small>

| ChemSpiderID = 180

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID1 = 1272049

| ChemSpiderID1_Ref = {{chemspidercite|changed|chemspider}}

| ChemSpiderID1_Comment = <small>''R''</small>

| ChemSpiderID2 = 64077

| ChemSpiderID2_Comment = <small>''S''</small>

| ChemSpiderID2_Ref = {{chemspidercite|changed|chemspider}}

| EINECS = 227-388-6

| DrugBank = DB04075

| DrugBank_Ref = {{drugbankcite|changed|drugbank}}

| KEGG = C00624

| KEGG_Ref = {{keggcite|changed|kegg}}

| MeSHName = N-acetylglutamate

| ChEBI = 17533

| ChEBI_Ref = {{ebicite|changed|EBI}}

| RTECS = LZ9725000 <small>''S''</small>

| Beilstein = 1727473 <small>''S''</small>

| 3DMet = B00147

| SMILES = CC(=O)NC(CCC(=O)O)C(=O)O

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| InChI1 = 1S/C7H11NO5/c1-4(9)8-5(7(12)13)2-3-6(10)11/h5H,2-3H2,1H3,(H,8,9)(H,10,11)(H,12,13)/t5-/m1/s1

| InChIKey1 = RFMMMVDNIPUKGG-RXMQYKEDSA-N

| InChI2 = 1S/C7H11NO5/c1-4(9)8-5(7(12)13)2-3-6(10)11/h5H,2-3H2,1H3,(H,8,9)(H,10,11)(H,12,13)/t5-/m0/s1

| InChIKey2 = RFMMMVDNIPUKGG-YFKPBYRVSA-N

}}

|Section2={{Chembox Properties

| C=7 | H=11 | N=1 | O=5

| Appearance = White crystals

| Density = 1 g mL⁻¹

| MeltingPtC = 191 to 194

| Solubility = 36 g L⁻¹

}}

|Section3={{Chembox Hazards

| LD50 = >7 g kg⁻¹ <small>(oral, rat)</small>

}}

|Section4={{Chembox Related

| OtherFunction_label = alkanoic acids

| OtherFunction = {{unbulleted list|[[n-Acetylaspartic acid|''N''-Acetylaspartic acid]]|[[Aceglutamide]]|[[Citrulline]]|[[Pivagabine]]}}

| OtherCompounds = {{unbulleted list|[[Bromisoval]]|[[Carbromal]]}}

}}

'''''N''-Acetylglutamic acid''' (also referred to as '''''N''-acetylglutamate''', abbreviated '''NAG''', chemical formula C₇H₁₁NO₅)<ref>{{Cite web|url=https://pubchem.ncbi.nlm.nih.gov/compound/N-Acetyl-L-glutamic_acid|title=''N''-Acetyl <small>L</small>-glutamic acid|last=Pubchem|website=pubchem.ncbi.nlm.nih.gov|language=en|access-date=2018-06-03}}</ref> is biosynthesized from [[glutamate]] and [[Acetylornithinase|acetylornithine]] by ornithine acetyltransferase, and from [[glutamic acid]] and [[acetyl-CoA]] by the enzyme [[N-acetylglutamate synthase|''N''-acetylglutamate synthase]]. The reverse reaction, hydrolysis of the acetyl group, is catalyzed by a specific [[hydrolase]]. It is the first intermediate involved in the biosynthesis of [[arginine]] in prokaryotes and simple eukaryotes and a regulator in the process known as the [[urea cycle]] that converts toxic ammonia to urea for excretion from the body in vertebrates.

== Discovery ==

''N''-Acetylglutamic acid is an extracellular [[metabolite]] isolated from the prokaryote [[Rhizobium]] trifolii that was characterized using many structure determination techniques such as [[proton nuclear magnetic resonance]] (¹H NMR) spectroscopy, [[Fourier-transform infrared spectroscopy]], and [[Gas chromatography–mass spectrometry|gas chromatography-mass spectrometry]].

In ''[[Rhizobium]]'', extracellular build-up of ''N''-acetylglutamic acid is due to metabolism involving [[nod factor]] genes on a [[Symbiosis|symbiotic]] [[plasmid]]. When the nod factors are mutated, less ''N''-acetylglutamic acid is produced.<ref name="Philip-Hollingsworth_19912">{{cite journal|vauthors=Philip-Hollingsworth S, Hollingsworth RI, Dazzo FB|date=September 1991|title=''N''-Acetylglutamic acid: an extracellular nod signal of ''Rhizobium trifolii'' ANU843 that induces root hair branching and nodule-like primordia in white clover roots|url=http://www.jbc.org/content/266/25/16854|journal=The Journal of Biological Chemistry|volume=266|issue=25|pages=16854–8|doi=10.1016/S0021-9258(18)55380-1|pmid=1885611|doi-access=free}}</ref>

== Biosynthesis ==

=== Prokaryotes and simple eukaryotes ===

In prokaryotes and simple eukaryotes, ''N''-acetylglutamic acid can be produced by [[N-Acetylglutamate synthase|''N''-acetylglutamate synthase]] (NAGS) or ornithine acetyltransferase (OAT).

==== Ornithine acetyltransferase (OAT) synthesis ====

OAT synthesizes ''N''-acetylglutamic acid from [[glutamate]] and [[Acetylornithinase|acetylornithine]] and is the method of choice for production in prokaryotes that have the ability to synthesize the compound [[ornithine]].<ref name="Caldovic_20032">{{cite journal|vauthors=Caldovic L, Tuchman M|date=June 2003|title=''N''-Acetylglutamate and its changing role through evolution|journal=The Biochemical Journal|volume=372|issue=Pt 2|pages=279–90|doi=10.1042/BJ20030002|pmc=1223426|pmid=12633501}}</ref>

==== ''N''-Acetylglutamate synthase (NAGS) synthesis ====

''N''-Acetylglutamate synthase is an enzyme that serves as a replenisher of ''N''-acetylglutamic acid to supplement any ''N''-acetylglutamic acid lost by the cell through [[mitosis]] or degradation. NAGS synthesizes ''N''-acetylglutamic acid by catalyzing the addition of an acetyl group from [[Acetyl-CoA|acetyl-coenzyme A]] to [[Glutamic acid|glutamate]]. In prokaryotes with non-cyclic ornithine production, NAGS is the sole method of ''N''-acetylglutamic acid synthesis and is inhibited by arginine.<ref name="Caldovic_20032" /> Acetylation of glutamate is thought to prevent glutamate from being used by [[proline]] biosynthesis.<ref name="Caldara_20082">{{cite journal|vauthors=Caldara M, Dupont G, Leroy F, Goldbeter A, De Vuyst L, Cunin R|date=March 2008|title=Arginine biosynthesis in ''Escherichia coli'': experimental perturbation and mathematical modeling|journal=The Journal of Biological Chemistry|volume=283|issue=10|pages=6347–58|doi=10.1074/jbc.M705884200|pmid=18165237|doi-access=free}}</ref>

=== Vertebrates ===

In contrast to prokaryotes, NAGS in mammals is enhanced by arginine, along with [[protamine]]s. It is inhibited by ''N''-acetylglutamic acid and its analogues (other ''N''-acetylated compounds).<ref name="Caldovic_20032" />

The brain also contains ''N''-acetylglutamic acid at trace amounts, however no expression of NAGS is found. This suggests that ''N''-acetylglutamic acid is produced by another enzyme in the brain that is yet to be determined.<ref name="Caldovic_20032" />

==Biological roles==

===Vertebrates and mammals===

In vertebrae and mammals, ''N''-acetylglutamic acid is the allosteric activator molecule to mitochondrial [[Carbamoyl phosphate synthetase I|carbamyl phosphate synthetase I]] (CPSI) which is the first enzyme in the urea cycle.<ref>{{Cite journal|last1=Auditore|first1=Joseph V.|last2=Wade|first2=Littleton|last3=Olson|first3=Erik J.|date=November 1966|title=Occurrence of ''N''-acetyl-<small>L</small>-glutamic Acid in the Human Brain|journal=Journal of Neurochemistry|language=en|volume=13|issue=11|pages=1149–1155|doi=10.1111/j.1471-4159.1966.tb04272.x|pmid=5924663|s2cid=43263361|issn=0022-3042}}</ref> It triggers the production of the first urea cycle intermediate, [[Carbamoyl phosphate|carbamyl phosphate]]. CPSI is inactive when ''N''-acetylglutamic acid is not present. In the liver and small intestines, ''N''-acetylglutamic acid-dependent CPSI produces [[citrulline]], the second intermediate in the urea cycle. Liver cell distribution of ''N''-acetylglutamic acid is highest in the mitochondria at 56% of total ''N''-acetylglutamic acid availability, 24% in the nucleus, and the remaining 20% in the cytosol. [[Aminoacylase]] I in liver and kidney cells degrades ''N''-acetylglutamic acid to glutamate and acetate.<ref name="Harper_20092">{{cite journal|vauthors=Harper MS, Amanda Shen Z, Barnett JF, Krsmanovic L, Myhre A, Delaney B|date=November 2009|title=''N''-Acetyl-glutamic acid: evaluation of acute and 28-day repeated dose oral toxicity and genotoxicity|journal=Food and Chemical Toxicology|volume=47|issue=11|pages=2723–9|doi=10.1016/j.fct.2009.07.036|pmid=19654033}}</ref> In contrast, ''N''-acetylglutamic acid is ''not'' the allosteric cofactor to carbamyl phosphate synthetase found in the cytoplasm, which is involved in [[pyrimidine]] synthesis.<ref name="Pelley_20072">{{cite book|title=Elsevier's Integrated Biochemistry|last=Pelley|first=John W.|date=2007|publisher=Elsevier|isbn=978-0-323-03410-4|pages=117–122|chapter=Chapter 14: Purine, Pyrimidine, and Single-Carbon Metabolism|doi=10.1016/b978-0-323-03410-4.50020-1|name-list-style=vanc}}</ref>

''N''-acetylglutamic acid concentrations increase when protein consumption increases due to the accumulation of ammonia that must be secreted through the urea cycle, which supports the role of ''N''-acetylglutamic acid as the cofactor for CPSI. Furthermore, ''N''-acetylglutamic acid can be found in many commonly consumed foods such as soy, corn, and coffee, with cocoa powder containing a notably high concentration.<ref name="Hession_20082">{{cite journal|vauthors=Hession AO, Esrey EG, Croes RA, Maxwell CA|date=October 2008|title=''N''-Acetylglutamate and ''N''-acetylaspartate in soybeans (''Glycine max'' L.), maize (''Zea mays'' L.), [corrected] and other foodstuffs|journal=Journal of Agricultural and Food Chemistry|volume=56|issue=19|pages=9121–6|doi=10.1021/jf801523c|pmid=18781757}}</ref>

Deficiency in ''N''-acetylglutamic acid in humans is an autosomal recessive disorder that results in blockage of urea production which ultimately increases the concentration of ammonia in the blood ([[hyperammonemia]]). Deficiency can be caused by defects in the NAGS coding gene or by deficiencies in the precursors essential for synthesis.<ref name="Caldovic_20032" />

===Bacteria===

''N''-Acetylglutamic acid is the second intermediate in the arginine production pathway in ''[[Escherichia coli]]'' and is produced via NAGS.<ref name="Caldara_20082" /> In this pathway, ''N''-acetylglutamic acid kinase (NAGK) catalyzes the phosphorylation of the gamma (third) carboxyl group of ''N''-acetylglutamic acid using the phosphate produced by [[hydrolysis]] of [[adenosine triphosphate]] (ATP).<ref name="Gil-Ortiz_20032">{{cite journal|vauthors=Gil Ortiz F, Ramón Maiques S, Fita I, Rubio V|date=August 2003|title=The course of phosphorus in the reaction of ''N''-acetyl-<small>L</small>-glutamate kinase, determined from the structures of crystalline complexes, including a complex with an {{chem|AlF|4|-}} transition state mimic|journal=Journal of Molecular Biology|volume=331|issue=1|pages=231–44|pmid=12875848|doi=10.1016/S0022-2836(03)00716-2}}</ref>

===White clover seedling roots===

''Rhizobium'' can form a symbiotic relationship with [[Trifolium repens|white clover]] seedling roots and form colonies. The extracellular ''N''-acetylglutamic acid produced by these bacteria have three morphological effects on the white clover seedling roots: branching of root hairs, swelling of root tips, and increase in the number of cell divisions in undifferentiated cells found on the outer-most cell layer of the root. This suggests that ''N''-acetylglutamic acid is involved in the stimulation of mitosis. The same effects were observed on the [[Trifolium fragiferum|strawberry clover]], but not in [[legume]]s. The effects of ''N''-acetylglutamic acid on the clover species were more potent than the effects from [[glutamine]], glutamate, arginine, or [[ammonia]].<ref name="Caldovic_20032" />

== Structure ==

[[File:NAG at physiological.png|thumb|149x149px|''N''-Acetylglutamic acid at physiological pH (7.4)]]

''N''-Acetylglutamic acid is composed of two carboxylic acid groups and an amide group protruding from the second carbon. The structure of ''N''-acetylglutamic acid at physiological [[pH]] (7.4) has all carboxyl groups [[Deprotonation|deprotonated]].

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=== Proton NMR spectroscopy ===

[[File:NAG_protons_exploded_(corrected).png|left|thumb|115x115px|''N''-acetylglutamic acid with protons shown]][[File:NAG_HNMR.png|thumb|373x373px|Proton NMR spectrum]]

The molecular structure of ''N''-acetylglutamic acid was determined using [[proton NMR spectroscopy]].<ref name="Philip-Hollingsworth_19912" /> Proton NMR reveals the presence and functional group location of protons based on [[chemical shift]]s recorded on the spectrum.<ref>{{Cite web|url=http://www.nmrdb.org/new_predictor/index.shtml?v=v2.87.7|title=Predict ¹H proton NMR spectra|website=www.nmrdb.org|access-date=2018-06-03}}</ref>

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=== ¹³C NMR spectroscopy ===

[[File:NAG_CNMR_2.png|thumb|373x373px|¹³C NMR Spectrum]]Like proton NMR, carbon-13 (¹³C) NMR spectroscopy is a method used in molecular structure determination. ¹³C NMR reveals the types of carbons present in a molecule based on chemical shifts that correspond to certain functional groups. ''N''-Acetylglutamic acid exhibits carbonyl carbons most distinctly due to the three carbonyl-containing substituents.<ref>{{Cite web|url=http://www.nmrdb.org/13c/index.shtml?v=v2.87.7|title=Predict ¹³C carbon NMR spectra|website=www.nmrdb.org|access-date=2018-06-03}}</ref>

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== See also ==

* [[Glutamate]]

* [[Glutamic acid]]

* [[Urea cycle]]

* [[Arginine]]

* [[Ornithine]]

== References ==

{{Reflist}}

== External links ==

* [http://www.biochemj.org/bj/372/0279/bj3720279f06.gif Diagram at biochemj.org]

{{DEFAULTSORT:Acetylglutamic acid, N-}}

[[Category:Acetamides]]

[[Category:Dicarboxylic acids]]

[[Category:Amino acid derivatives]]