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MetaCyc Pathway: UDP-N-acetyl-D-glucosamine biosynthesis II

Enzyme View:

This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Synonyms: UDP-N-acetylgalactosamine biosynthesis

Superclasses: Biosynthesis Amines and Polyamines Biosynthesis UDP-N-acetyl-D-glucosamine Biosynthesis

Some taxa known to possess this pathway include ? : Aedes aegypti , Arabidopsis thaliana col , Candida albicans , Drosophila melanogaster , Homo sapiens , Mus musculus , Rattus norvegicus , Saccharomyces cerevisiae , Sus scrofa

Expected Taxonomic Range: Eukaryota

Summary:
In both eukaryotes and prokaryotes, sugar and amino sugar residues are converted to sugar nucleotides prior to their incorporation into structural polysaccharides via UDP-sugar transferases. In this pathway, UDP-N-acetyl-D-glucosamine (UDP-GlcNAc) is the amino sugar nucleotide donor of N-acetyl-D-glucosamine (GlcNAc) residues for the biosynthesis of glycosylated proteins and cell surface structures. Two variations of this pathway exist, one in eukaryotes and one in prokaryotes. In the eukaryotic pathway shown here, fructose-6-phosphate produced during glycolysis (see pathway glycolysis VI (metazoan)) is transaminated and isomerized to glucosamine-6-phosphate, followed by acetylation to N-acetyl-D-glucosamine-6-phosphate, isomerization to N-acetyl-D-glucosamine-1-phosphate, and uridylation to UDP-GlcNAc. In prokaryotes, the first and last reactions are similar to those of eukaryotes, but in the second and third reactions, glucosamine-6-phosphate is isomerized to glucosamine-1-phosphate, followed by its N acetylation to N-acetyl-D-glucosamine-1-phosphate (see pathway UDP-N-acetyl-D-glucosamine biosynthesis I). Reviewed in [Milewski06].

In eukaryotes this cytosolic pathway is highly regulated. UDP-GlcNAc donates GlcNAc residues for the biosynthesis of several classes of compounds, including N-linked glycans (see pathway dolichyl-diphosphooligosaccharide biosynthesis), glycosylphosphatidylinositol (GPI)-anchored proteins, glycolipids, and chitin, a homopolymer of GlcNac (in [Bulik03]). This pathway has been well studied both genetically and biochemically in yeast. The first committed, rate-limiting, step in hexosamine de novo biosynthesis is catalyzed by glucosamine-6-phosphate synthase (glutamine-fructose-6-phosphate amidotransferase). It is essentially irreversible and is regulated at the transcriptional and posttranslational levels, including feedback inhibition by UDP-GlcNAc (reviewed in [Milewski06]).

In some bacteria, some fungi (but not yeast), and metazoa, UDP-GlcNAc can be converted to UDP-N-acetyl-D-galactosamine by UDP-N-acetyl-D-glucosamine 4-epimerase. N-acetyl-D-galactosamine is a component of several different kinds of cell surface structures and glycosylated proteins (see pathway UDP-N-acetyl-D-galactosamine biosynthesis I). A UDP-N-acetylglucosamine 2-epimerase (EC 5.1.3.14) produces UDP-N-acetyl-D-mannosamine for N-glycosylated mannoprotein biosynthesis. Reviewed in [Milewski06].

Citations: [Overbeek98]

Superpathways: chitin biosynthesis

Variants: UDP-N-acetyl-D-glucosamine biosynthesis I

Credits:
Created 21-Aug-1998 by Ying HC , SRI International
Revised 01-May-2007 by Fulcher CA , SRI International


References

Bulik03: Bulik DA, Olczak M, Lucero HA, Osmond BC, Robbins PW, Specht CA (2003). "Chitin synthesis in Saccharomyces cerevisiae in response to supplementation of growth medium with glucosamine and cell wall stress." Eukaryot Cell 2(5);886-900. PMID: 14555471

Milewski06: Milewski S, Gabriel I, Olchowy J (2006). "Enzymes of UDP-GlcNAc biosynthesis in yeast." Yeast 23(1);1-14. PMID: 16408321

Overbeek98: Overbeek, R, Larsen, N, Selkov, EE, Maltsev, M "The WIT Database." 1998 WWW URL http://www.cme.msu.edu/WIT/.

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

Badet87: Badet B, Vermoote P, Haumont PY, Lederer F, LeGoffic F (1987). "Glucosamine synthetase from Escherichia coli: purification, properties, and glutamine-utilizing site location." Biochemistry 1987;26(7);1940-8. PMID: 3297136

Badet88: Badet B, Vermoote P, Le Goffic F (1988). "Glucosamine synthetase from Escherichia coli: kinetic mechanism and inhibition by N3-fumaroyl-L-2,3-diaminopropionic derivatives." Biochemistry 1988;27(7);2282-7. PMID: 3132968

BadetDenisot92: Badet-Denisot MA, Badet B (1992). "Chemical modification of glucosamine-6-phosphate synthase by diethyl pyrocarbonate: evidence of histidine requirement for enzymatic activity." Arch Biochem Biophys 1992;292(2);475-8. PMID: 1731613

BadetDenisot95: Badet-Denisot MA, Leriche C, Massiere F, Badet B (1995). "Nitrogen transfer in E. coli glucosamine-6P synthase. Investigations using substrate and bisubstrate analogs." Bioorg. Med. Chem. Lett. 5(8);815-820.

Bearne00: Bearne SL, Blouin C (2000). "Inhibition of Escherichia coli glucosamine-6-phosphate synthase by reactive intermediate analogues. The role of the 2-amino function in catalysis." J Biol Chem 275(1);135-40. PMID: 10617596

Bearne95: Bearne SL, Wolfenden R (1995). "Glutamate gamma-semialdehyde as a natural transition state analogue inhibitor of Escherichia coli glucosamine-6-phosphate synthase." Biochemistry 34(36);11515-20. PMID: 7547881

Bearne96: Bearne SL (1996). "Active site-directed inactivation of Escherichia coli glucosamine-6-phosphate synthase. Determination of the fructose 6-phosphate binding constant using a carbohydrate-based inactivator." J Biol Chem 271(6);3052-7. PMID: 8621700

Boehmelt00: Boehmelt G, Fialka I, Brothers G, McGinley MD, Patterson SD, Mo R, Hui CC, Chung S, Huber LA, Mak TW, Iscove NN (2000). "Cloning and characterization of the murine glucosamine-6-phosphate acetyltransferase EMeg32. Differential expression and intracellular membrane association." J Biol Chem 275(17);12821-32. PMID: 10777580

BRENDA14: BRENDA team (2014). "Imported from BRENDA version existing on Aug 2014." http://www.brenda-enzymes.org.

Broschat02: Broschat KO, Gorka C, Page JD, Martin-Berger CL, Davies MS, Huang Hc HC, Gulve EA, Salsgiver WJ, Kasten TP (2002). "Kinetic characterization of human glutamine-fructose-6-phosphate amidotransferase I: potent feedback inhibition by glucosamine 6-phosphate." J Biol Chem 277(17);14764-70. PMID: 11842094

Brown99: Brown K, Pompeo F, Dixon S, Mengin-Lecreulx D, Cambillau C, Bourne Y (1999). "Crystal structure of the bifunctional N-acetylglucosamine 1-phosphate uridyltransferase from Escherichia coli: a paradigm for the related pyrophosphorylase superfamily." EMBO J 18(15);4096-107. PMID: 10428949

Chi09: Chi A, Rhee S (2009). "The functional annotation of Arabidopsis protein sequences was performed by BLAST queries against a reference set of experimentally verified enzymes. For each Arabidopsis sequence, the enzymatic activity of the top BLAST hit (or hits if they had equivalent E-values) was assigned to the protein if its E-value fell below a specific E-value threshold established for the corresponding enzymatic activity. Note: The annotation thresholds were established by doing a self BLAST of the reference enzyme dataset. For each enzymatic activity represented by multiple proteins, the mean E-value of all the correct hits generated by the self BLAST was selected as the cut-off. All of these means were averaged and used as the cut-off for assigning annotations for any enzymatic activities that were represented by a single protein in the reference dataset."

Chmara84: Chmara H, Zahner H (1984). "The inactivation of glucosamine synthetase from bacteria by anticapsin, the C-terminal epoxyamino acid of the antibiotic tetaine." Biochim Biophys Acta 787(1);45-52. PMID: 6426523

Chmara85: Chmara H (1985). "Inhibition of glucosamine synthase by bacilysin and anticapsin." J Gen Microbiol 131(2);265-71. PMID: 3884731

De96a: De Luca C, Lansing M, Crescenzi F, Martini I, Shen GJ, O'Regan M, Wong CH (1996). "Overexpression, one-step purification and characterization of UDP-glucose dehydrogenase and UDP-N-acetylglucosamine pyrophosphorylase." Bioorg Med Chem 4(1);131-41. PMID: 8689233

Deng06: Deng MD, Grund AD, Wassink SL, Peng SS, Nielsen KL, Huckins BD, Burlingame RP (2006). "Directed evolution and characterization of Escherichia coli glucosamine synthase." Biochimie 88(5);419-29. PMID: 16871653

Durand08: Durand P, Golinelli-Pimpaneau B, Mouilleron S, Badet B, Badet-Denisot MA (2008). "Highlights of glucosamine-6P synthase catalysis." Arch Biochem Biophys 474(2);302-17. PMID: 18279655

DutkaMalen88: Dutka-Malen S, Mazodier P, Badet B (1988). "Molecular cloning and overexpression of the glucosamine synthetase gene from Escherichia coli." Biochimie 70(2);287-90. PMID: 3134953

Fang09: Fang J, Guan W, Cai L, Gu G, Liu X, Wang PG (2009). "Systematic study on the broad nucleotide triphosphate specificity of the pyrophosphorylase domain of the N-acetylglucosamine-1-phosphate uridyltransferase from Escherichia coli K12." Bioorg Med Chem Lett 19(22);6429-32. PMID: 19804974

Floquet07: Floquet N, Mouilleron S, Daher R, Maigret B, Badet B, Badet-Denisot MA (2007). "Ammonia channeling in bacterial glucosamine-6-phosphate synthase (Glms): molecular dynamics simulations and kinetic studies of protein mutants." FEBS Lett 581(16);2981-7. PMID: 17559838

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Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Fri Nov 28, 2014, biocyc12.