2.02012-08-09 09:25:27 -06002015-06-03 17:21:47 -0600ECMDB21561M2MDB001956N-AcetylglucosamineN-Acetyl-D-Glucosamine (N-acetlyglucosamine, GlcNAc) is a monosaccharide derivative of glucose. Chemically it is an amide between glucosamine and acetic acid. It is part of peptidoglycan, a biopolymer in bacterial cell walls, built from alternating units of GlcNAc and N-acetylmuramic acid (MurNAc), cross-linked with oligopeptides at the lactic acid residue of MurNAc. It is a key component of peptidoglycan synthesis. The peptidoglycan synthesis pathway starts at the cytoplasm, where in six steps the peptidoglycan precursor a UDP-N-acetylmuramoyl-pentapeptide is synthesized. This precursor is then attached to the memberane acceptor all-trans-undecaprenyl phosphate, generating a N-acetylmuramoyl-pentapeptide-diphosphoundecaprenol, also known as lipid I. Another transferase then adds UDP-N-acetyl-D-glucosamine, yielding the complete monomeric unit a lipid II, also known as lipid II. This final lipid intermediate is transferred through the membrane. The peptidoglycan monomers are then polymerized on the outside surface by glycosyltransferases, which form the linear glycan chains, and transpeptidases, which catalyze the formation of peptide crosslinks.2-(acetylamino)-2-Deoxy-b-D-glucopyranose2-(Acetylamino)-2-deoxy-beta-D-glucopyranose2-(Acetylamino)-2-deoxy-D-Glucose2-(acetylamino)-2-Deoxy-β-D-glucopyranose2-(Acetylamino)-2-deoxyhexose2-(Acetylamino)-2-deoxyhexose (ACD/Name 4.0)2-acetamido-2-Deoxy-b-D-glucopyranose2-Acetamido-2-deoxy-beta-D-glucopyranose2-Acetamido-2-deoxy-D-glucose2-acetamido-2-Deoxy-β-D-glucopyranose2-Acetamido-2-deoxyglucose2-Acetamido-2-deoxyhexopyranose2-Acetamido-D-glucose2-Acetylamino-2-deoxy-D-glucose<i>N</i>-acetylglucosamineAcetylglucosamineBetaGlcNAcD-N-AcetylglucosamineGlcnacGlcNAc-bGlcNAc-betaGlcNAc-βGlucosamine ComplexN-Acetyl-b-D-glucosamineN-Acetyl-beta-D-glucosamineN-Acetyl-D-glucosamineN-Acetyl-D-hexosamineN-Acetyl-β-D-glucosamineN-AcetylchitosamineN-AcetylglucosamineNAcGlcNAGC8H15NO6221.2078221.089937217N-[(3R,4R,5S,6R)-2,4,5-trihydroxy-6-(hydroxymethyl)oxan-3-yl]acetamideGlcNAc7512-17-6CC(=O)N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1OInChI=1S/C8H15NO6/c1-3(11)9-5-7(13)6(12)4(2-10)15-8(5)14/h4-8,10,12-14H,2H2,1H3,(H,9,11)/t4-,5-,6-,7-,8?/m1/s1OVRNDRQMDRJTHS-RTRLPJTCSA-NSolidlogp-2.60logs0.06solubility2.54e+02 g/lmelting_point210 oClogp-3.2pka_strongest_acidic11.6pka_strongest_basic-0.78iupacN-[(3R,4R,5S,6R)-2,4,5-trihydroxy-6-(hydroxymethyl)oxan-3-yl]acetamideaverage_mass221.2078mono_mass221.089937217smilesCC(=O)N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1OformulaC8H15NO6inchiInChI=1S/C8H15NO6/c1-3(11)9-5-7(13)6(12)4(2-10)15-8(5)14/h4-8,10,12-14H,2H2,1H3,(H,9,11)/t4-,5-,6-,7-,8?/m1/s1inchikeyOVRNDRQMDRJTHS-RTRLPJTCSA-Npolar_surface_area119.25refractivity47.02polarizability20.56rotatable_bond_count2acceptor_count6donor_count5physiological_charge0formal_charge0Amino sugar and nucleotide sugar metabolism IThe synthesis of amino sugars and nucleotide sugars starts with the phosphorylation of N-Acetylmuramic acid (MurNac) through its transport from the periplasmic space to the cytoplasm. Once in the cytoplasm, MurNac and water undergo a reversible reaction through a N-acetylmuramic acid 6-phosphate etherase, producing a D-lactic acid and N-Acetyl-D-Glucosamine 6-phosphate. This latter compound can also be introduced into the cytoplasm through a phosphorylating PTS permase in the inner membrane that allows for the transport of N-Acetyl-D-glucosamine from the periplasmic space. N-Acetyl-D-Glucosamine 6-phosphate can also be obtained from chitin dependent reactions. Chitin is hydrated through a bifunctional chitinase to produce chitobiose. This in turn gets hydrated by a beta-hexosaminidase to produce N-acetyl-D-glucosamine. The latter undergoes an atp dependent phosphorylation leading to the production of N-Acetyl-D-Glucosamine 6-phosphate.
N-Acetyl-D-Glucosamine 6-phosphate is then be deacetylated in order to produce Glucosamine 6-phosphate through a N-acetylglucosamine-6-phosphate deacetylase. This compound can either be isomerized or deaminated into Beta-D-fructofuranose 6-phosphate through a glucosamine-fructose-6-phosphate aminotransferase and a glucosamine-6-phosphate deaminase respectively.
Glucosamine 6-phosphate undergoes a reversible reaction to glucosamine 1 phosphate through a phosphoglucosamine mutase. This compound is then acetylated through a bifunctional protein glmU to produce a N-Acetyl glucosamine 1-phosphate.
N-Acetyl glucosamine 1-phosphate enters the nucleotide sugar synthesis by reacting with UTP and hydrogen ion through a bifunctional protein glmU releasing pyrophosphate and a Uridine diphosphate-N-acetylglucosamine.This compound can either be isomerized into a UDP-N-acetyl-D-mannosamine or undergo a reaction with phosphoenolpyruvic acid through UDP-N-acetylglucosamine 1-carboxyvinyltransferase releasing a phosphate and a UDP-N-Acetyl-alpha-D-glucosamine-enolpyruvate.
UDP-N-acetyl-D-mannosamine undergoes a NAD dependent dehydrogenation through a UDP-N-acetyl-D-mannosamine dehydrogenase, releasing NADH, a hydrogen ion and a UDP-N-Acetyl-alpha-D-mannosaminuronate, This compound is then used in the production of enterobacterial common antigens.
UDP-N-Acetyl-alpha-D-glucosamine-enolpyruvate is reduced through a NADPH dependent UDP-N-acetylenolpyruvoylglucosamine reductase, releasing a NADP and a UDP-N-acetyl-alpha-D-muramate. This compound is involved in the D-glutamine and D-glutamate metabolism.
PW000886MetabolicAmino sugar and nucleotide sugar metabolism IIThe synthesis of amino sugars and nucleotide sugars starts with the phosphorylation of N-Acetylmuramic acid (MurNac) through its transport from the periplasmic space to the cytoplasm. Once in the cytoplasm, MurNac and water undergo a reversible reaction through a N-acetylmuramic acid 6-phosphate etherase, producing a D-lactic acid and N-Acetyl-D-Glucosamine 6-phosphate. This latter compound can also be introduced into the cytoplasm through a phosphorylating PTS permase in the inner membrane that allows for the transport of N-Acetyl-D-glucosamine from the periplasmic space. N-Acetyl-D-Glucosamine 6-phosphate can also be obtained from chitin dependent reactions. Chitin is hydrated through a bifunctional chitinase to produce chitobiose. This in turn gets hydrated by a beta-hexosaminidase to produce N-acetyl-D-glucosamine. The latter undergoes an atp dependent phosphorylation leading to the production of N-Acetyl-D-Glucosamine 6-phosphate.
N-Acetyl-D-Glucosamine 6-phosphate is then be deacetylated in order to produce Glucosamine 6-phosphate through a N-acetylglucosamine-6-phosphate deacetylase. This compound is then deaminased into Beta-D-fructofuranose 6-phosphate through a glucosamine-6-phosphate deaminase.
The beta-D-fructofuranose 6 -phosphate is isomerized in a reversible reaction into an alpha-D-mannose 6-phosphate. This compound can also be introduced into the cell from the periplasmic space through a mannose PTS permease that phosphorylates an alpha-D-mannose. Alpha-D-mannose 6-phosphate undergoes a reversible reaction through a phosphomannomutase to produce an alpha-D-mannose 1-phosphate.
The alpha-D-mannose 1-phosphate enters the nucleotide sugar metabolism through a reaction with GTP producing a GDP-mannose and releasing a pyrophosphate, all through a mannose-1-phosphate guanylyltransferase. GDP-mannose is then dehydrated to produce GDP-4-dehydro-6-deoxy-alpha-D-mannose through a GDP-mannose 4,6-dehydratase. This compound is then used to synthesize GDP-Beta-L-fucose through a NADPH dependent GDP-L-fucose synthase.
Alpha-D-glucose is introduced into the cytoplasm through a glucose PTS permease, which phosphorylates the compound in order to produce an alpha-D-glucose 6-phosphate. This compound is then modified through a phosphoglucomutase 1 to yield alpha-D-glucose 1-phosphate. This compound can either be adenylated to produce ADP-glucose or uridylylated to produce galactose 1-phosphate through glucose-1-phosphate adenyllyltransferase and galactose-1-phosphate uridylyltransferase respectively.PW000887MetabolicAmino sugar and nucleotide sugar metabolism IIIThe synthesis of amino sugars and nucleotide sugars starts with the phosphorylation of N-Acetylmuramic acid (MurNac) through its transport from the periplasmic space to the cytoplasm. Once in the cytoplasm, MurNac and water undergo a reversible reaction through a N-acetylmuramic acid 6-phosphate etherase, producing a D-lactic acid and N-Acetyl-D-Glucosamine 6-phosphate. This latter compound can also be introduced into the cytoplasm through a phosphorylating PTS permase in the inner membrane that allows for the transport of N-Acetyl-D-glucosamine from the periplasmic space. N-Acetyl-D-Glucosamine 6-phosphate can also be obtained from chitin dependent reactions. Chitin is hydrated through a bifunctional chitinase to produce chitobiose. This in turn gets hydrated by a beta-hexosaminidase to produce N-acetyl-D-glucosamine. The latter undergoes an atp dependent phosphorylation leading to the production of N-Acetyl-D-Glucosamine 6-phosphate.
N-Acetyl-D-Glucosamine 6-phosphate is then be deacetylated in order to produce Glucosamine 6-phosphate through a N-acetylglucosamine-6-phosphate deacetylase. This compound is then deaminased into Beta-D-fructofuranose 6-phosphate through a glucosamine-6-phosphate deaminase.
Beta-D-fructofuranose 6-phosphate is isomerized into a beta-D-glucose 6-phosphate through a glucose-6-phosphate isomerase. The compound is then isomerized by a putative beta-phosphoglucomutase to produce a beta-D-glucose 1-phosphate. This compound enters the nucleotide sugar metabolism through uridylation resulting in a UDP-glucose. UDP-glucose is then dehydrated through a UDP-glucose 6-dehydrogenase to produce a UDP-glucuronic acid. This compound undergoes a NAD dependent reaction through a bifunctional polymyxin resistance protein to produce UDP-Beta-L-threo-pentapyranos-4-ulose. This compound then reacts with L-glutamic acid through a UDP-4-amino-4-deoxy-L-arabinose--oxoglutarate aminotransferase to produce an oxoglutaric acid and UDP-4-amino-4-deoxy-beta-L-arabinopyranose
The latter compound interacts with a N10-formyl-tetrahydrofolate through a bifunctional polymyxin resistance protein ArnA, resulting in a tetrahydrofolate, a hydrogen ion and a UDP-4-deoxy-4-formamido-beta-L-arabinopyranose, which in turn reacts with a product of the methylerythritol phosphate and polysoprenoid biosynthesis pathway, di-trans,octa-cis-undecaprenyl phosphate to produce a 4-deoxy-4-formamido-alpha-L-arabinopyranosyl ditrans, octacis-undecaprenyl phosphate.
Alpha-D-glucose is introduced into the cytoplasm through a glucose PTS permease, which phosphorylates the compound in order to produce an alpha-D-glucose 6-phosphate. This compound is then modified through a phosphoglucomutase 1 to yield alpha-D-glucose 1-phosphate. This compound can either be adenylated to produce ADP-glucose or uridylylated to produce galactose 1-phosphate through glucose-1-phosphate adenyllyltransferase and galactose-1-phosphate uridylyltransferase respectively.PW000895Metabolicinner membrane transportlist of inner membrane transport complexes, transporting compounds from the periplasmic space to the cytosol
This pathway should be updated regularly with the new inner membrae transports addedPW000786Metabolic1,6-anhydro-<i>N</i>-acetylmuramic acid recyclingAnhydromuropeptides (mainly GlcNAc-1,6-anhMurNAc-L-Ala-γ-D-Glu-DAP-D-Ala) are steadily released during growth by lytic transglycosylases and endopeptidases and imported back into the cytoplasm for recycling. During bacterial growth, a very large proportion of the peptidoglycan polymer is degraded and reused in a process termed cell wall recycling. For example, the Gram-negative bacterium Escherichia coli recovers about half of its cell wall within one generation.
The anhydromuropeptides are imported by the ampG-encoded muropeptide:H+ symporter. Once inside the cytoplasm, the anhydromuropeptides are hydrolyzed by N-acetylmuramoyl-L-alanine amidase (ampD), β-N-acetylhexosaminidase (nagZ) and L,D-carboxypeptidase A (ldcA), yielding N-acetyl-β-D-glucosamine, 1,6-anhydro-N-acetyl-β-muramate, L-alanyl-γ-D-glutamyl-meso-diaminopimelate and D-alanine.
1,6-anhydro-N-acetyl-β-muramate is phosphorylated by anhydro-N-acetylmuramic acid kinase (anmK) and then converted into N-acetyl-D-glucosamine 6-phosphate by N-acetylmuramic acid 6-phosphate etherase (murQ). This is a branch point, as this compound could be directed either for further degradation or for recycling into new peptidoglycan monomers, as described in this pathway. The final product of this pathway, UDP-N-acetyl-α-D-muramate, is one of the precursors for peptidoglycan biosynthesis.
The tripeptide L-alanyl-γ-D-glutamyl-meso-diaminopimelate, which is generated by muramoyltetrapeptide carboxypeptidase, can be degraded further, as described in muropeptide degradation. However, the vast majority is recycled by muropeptide ligase (mpl). This enzyme is a dedicated recycling enzyme that attaches the recovered Ala-Glu-DAP tripeptide to UDP-N-acetyl-α-D-muramate, thereby substituting three amino acid ligases of the peptidoglycan de novobiosynthetic pathway.
Although exogenously provided 1,6-anhydro-N-acetyl-β-muramate can be taken up by Escherichia coli, it can not serve as the sole source of carbon for growth, suggesting that it may be toxic to the cell. (EcoCyc)
PW002064MetabolicSpecdb::CMs22568Specdb::CMs30389Specdb::CMs30630Specdb::CMs30631Specdb::CMs30887Specdb::CMs30888Specdb::CMs30889Specdb::CMs37364Specdb::CMs99541Specdb::CMs99542Specdb::CMs99543Specdb::CMs99544Specdb::CMs99545Specdb::CMs99546Specdb::CMs146682Specdb::CMs1054770Specdb::CMs1054772Specdb::CMs1054774Specdb::CMs1054776Specdb::CMs1054778Specdb::CMs1054780Specdb::CMs1054782Specdb::CMs1054784Specdb::CMs1054786Specdb::CMs1054788Specdb::NmrOneD142950Specdb::NmrOneD142951Specdb::NmrOneD142952Specdb::NmrOneD142953Specdb::NmrOneD142954Specdb::NmrOneD142955Specdb::NmrOneD142956Specdb::NmrOneD142957Specdb::NmrOneD142958Specdb::NmrOneD142959Specdb::NmrOneD142960Specdb::NmrOneD142961Specdb::NmrOneD142962Specdb::NmrOneD142963Specdb::NmrOneD142964Specdb::NmrOneD142965Specdb::NmrOneD142966Specdb::NmrOneD142967Specdb::NmrOneD142968Specdb::NmrOneD142969Specdb::MsMs23636Specdb::MsMs23637Specdb::MsMs23638Specdb::MsMs30434Specdb::MsMs30435Specdb::MsMs30436Specdb::MsMs2240252Specdb::MsMs2241435Specdb::MsMs2244441Specdb::MsMs2245680Specdb::MsMs2246179Specdb::MsMs2246516Specdb::MsMs2247756Specdb::MsMs2248127Specdb::MsMs2248638Specdb::MsMs2249752Specdb::MsMs2250679Specdb::MsMs2251710Specdb::MsMs2792543Specdb::MsMs2792544Specdb::MsMs2792545Specdb::MsMs2915942Specdb::MsMs2915943Specdb::MsMs2915944HMDB00215439174388319C0014028009N-ACETYL-D-GLUCOSAMINEN-Acetylglucosaminevan der Werf, M. J., Overkamp, K. M., Muilwijk, B., Coulier, L., Hankemeier, T. (2007). "Microbial metabolomics: toward a platform with full metabolome coverage." Anal Biochem 370:17-25.17765195Slawson, C., Housley, M. P., Hart, G. W. (2006). "O-GlcNAc cycling: how a single sugar post-translational modification is changing the way we think about signaling networks." J Cell Biochem 97:71-83.16237703Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y, Nyati MK, Ahsan A, Kalyana-Sundaram S, Han B, Cao X, Byun J, Omenn GS, Ghosh D, Pennathur S, Alexander DC, Berger A, Shuster JR, Wei JT, Varambally S, Beecher C, Chinnaiyan AM: Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature. 2009 Feb 12;457(7231):910-4.19212411Nakagawa F, Schulte BA, Spicer SS: Lectin cytochemical evaluation of somatosensory neurons and their peripheral and central processes in rat and man. 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Carbohydr Res. 1992 Apr 10;228(1):265-76.1366057Kottgen E, Hell B, Muller C, Kainer F, Tauber R: Developmental changes in the glycosylation and binding properties of human fibronectins. Characterization of the glycan structures and ligand binding of human fibronectins from adult plasma, cord blood and amniotic fluid. Biol Chem Hoppe Seyler. 1989 Dec;370(12):1285-94.2619923Madrid JF, Castells MT, Martinez-Menarguez JA, Aviles M, Hernandez F, Ballesta J: Subcellular characterization of glycoproteins in the principal cells of human gallbladder. A lectin cytochemical study. Histochemistry. 1994 Mar;101(3):195-204.8056619Weiner B, Fischer T, Waxman S: Hemostasis in the era of the chronic anticoagulated patient. J Invasive Cardiol. 2003 Nov;15(11):669-73; quiz 674.14608143Yates AD, Watkins WM: Enzymes involved in the biosynthesis of glycoconjugates. A UDP-2-acetamido-2-deoxy-D-glucose: beta-D-galactopyranosyl-(1 leads to 4)-saccharide (1 leads to 3)-2-acetamido-2-deoxy-beta-D- glucopyranosyltransferase in human serum. Carbohydr Res. 1983 Aug 16;120:251-68.6226355PTS system N-acetylglucosamine-specific EIICBA componentP09323PTW3C_ECOLInagEhttp://ecmdb.ca/proteins/P09323.xmlProbable bifunctional chitinase/lysozymeP13656CHIA_ECOLIchiAhttp://ecmdb.ca/proteins/P13656.xmlBeta-hexosaminidaseP75949NAGZ_ECOLInagZhttp://ecmdb.ca/proteins/P75949.xmlN-acetyl-D-glucosamine kinaseP75959NAGK_ECOLInagKhttp://ecmdb.ca/proteins/P75959.xmlPTS system N-acetylglucosamine-specific EIICBA componentP09323PTW3C_ECOLInagEhttp://ecmdb.ca/proteins/P09323.xmlProbable bifunctional chitinase/lysozymeP13656CHIA_ECOLIchiAhttp://ecmdb.ca/proteins/P13656.xmlAdenosine triphosphate + N-Acetylglucosamine > ADP + N-Acetyl-D-Glucosamine 6-PhosphateN-Acetyl-D-glucosamine + Adenosine triphosphate + N-Acetylglucosamine > N-Acetyl-D-Glucosamine 6-Phosphate + Adenosine diphosphate + Hydrogen ion + N-Acetyl-D-Glucosamine 6-Phosphate + ADPPW_R003308Water + Chitobiose + Chitobiose >2 N-Acetyl-D-glucosamine +2 N-AcetylglucosaminePW_R003309Chitin + Water > N-Acetyl-D-glucosamine + Chitin + N-AcetylglucosaminePW_R003311N-Acetyl-D-glucosamine + HPr - phosphorylated + N-Acetylglucosamine > N-Acetyl-D-Glucosamine 6-Phosphate + HPr + N-Acetyl-D-Glucosamine 6-PhosphatePW_RCT000127N-acetyl-β-D-glucosamine(anhydrous)-N-acetylmuramate + Water > N-Acetylglucosamine + anhydro-n-acetylmuramic acidPW_R006026