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
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 III (from glucose)) 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 protein N-glycosylation (eukaryotic, high mannose)), 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 126.96.36.199) produces UDP-N-acetyl-D-mannosamine for N-glycosylated mannoprotein biosynthesis. Reviewed in [Milewski06].
Superpathways: chitin biosynthesis
Aam10: Aam BB, Heggset EB, Norberg AL, Sorlie M, Varum KM, Eijsink VG (2010). "Production of chitooligosaccharides and their potential applications in medicine." Mar Drugs 8(5);1482-517. PMID: 20559485
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
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
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
De96: 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
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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