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MetaCyc Pathway: L-glutamine biosynthesis I
Traceable author statement to experimental support

Enzyme View:

Pathway diagram: L-glutamine biosynthesis I

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: L-glutamine - L-glutamate pathway

Superclasses: BiosynthesisAmino Acids BiosynthesisProteinogenic Amino Acids BiosynthesisL-glutamine Biosynthesis
Degradation/Utilization/AssimilationInorganic Nutrients MetabolismNitrogen Compounds MetabolismAmmonia Assimilation

Some taxa known to possess this pathway include : Escherichia coli K-12 substr. MG1655, Haloferax mediterranei, Homo sapiens, Ruminococcus albus 8, Saccharomyces cerevisiae, Synechococcus elongatus PCC 7942

Expected Taxonomic Range: Archaea, Bacteria , Eukaryota

General background

The amino acid glutamine is a constituent of proteins and a nitrogen donor for many biosynthetic reactions, including the biosynthesis of amino acids, purines, pyrimidines, glucosamime and carbamoyl phosphate. The biosynthesis of glutamine is catalyzed by glutamine synthetase, a key enzyme of nitrogen metabolism found in all domains of life. Phylogenetic analysis of glutamine synthetase genes has suggested that they are among the oldest functioning genes in the history of evolution [Kumada93]. In microorganisms and plants, glutamine synthetase (also known as GS) has a role in ammonia assimilation in combination with glutamate synthase (glutamine: α-oxoglutarate aminotransferase, or GOGAT) as indicated by the pathway links and pathways ammonia assimilation cycle III and superpathway of ammonia assimilation (plants)). This is known as the GS/GOGAT pathway [Gottschalk86].

About this pathway

Three types of glutamine synthetases have been described, differing in number of subunits. The active site residues of all three types are conserved.

Glutamine synthetase type I is found mostly in bacteria and archaea, including Escherichia coli K-12 and Salmonella enterica enterica serovar Typhimurium (reviewed in [Stadtman01]). It is a well-studied homododecamer built from two back-to-back hexameric rings.

Glutamine synthetase type II is found mostly in eukaryotes and some soil bacteria, but it has also been described in the halophilic archaeon Haloferax mediterranei [MartinezEspinos06, Llorca06]. It is a homooctamer.

Glutamine synthetase type III has been described in anaerobic bacteria (such as Ruminococcus albus 8) and cyanobacteria, and is generally a homohexamer [Amaya05].

Superpathways: L-glutamate and L-glutamine biosynthesis, ammonia assimilation cycle III, ammonia assimilation cycle I, superpathway of ammonia assimilation (plants)

Variants: ammonia assimilation cycle II, L-glutamine biosynthesis III

Unification Links: EcoCyc:GLNSYN-PWY, YeastCyc:GLNSYN-PWY

Created 31-Jul-1995 by Riley M, Marine Biological Laboratory
Revised 11-Apr-2007 by Fulcher CA, SRI International
Last-Curated 27-Jun-2007 by Shearer A, SRI International


Amaya05: Amaya KR, Kocherginskaya SA, Mackie RI, Cann IK (2005). "Biochemical and mutational analysis of glutamine synthetase type III from the rumen anaerobe Ruminococcus albus 8." J Bacteriol 187(21);7481-91. PMID: 16237031

Gottschalk86: Gottschalk, G "Bacterial Metabolism, Second Edition." Springer-Verlag, New York. 1986.

Kumada93: Kumada Y, Benson DR, Hillemann D, Hosted TJ, Rochefort DA, Thompson CJ, Wohlleben W, Tateno Y (1993). "Evolution of the glutamine synthetase gene, one of the oldest existing and functioning genes." Proc Natl Acad Sci U S A 90(7);3009-13. PMID: 8096645

Llorca06: Llorca O, Betti M, Gonzalez JM, Valencia A, Marquez AJ, Valpuesta JM (2006). "The three-dimensional structure of an eukaryotic glutamine synthetase: functional implications of its oligomeric structure." J Struct Biol 156(3);469-79. PMID: 16884924

MartinezEspinos06: Martinez-Espinosa RM, Esclapez J, Bautista V, Bonete MJ (2006). "An octameric prokaryotic glutamine synthetase from the haloarchaeon Haloferax mediterranei." FEMS Microbiol Lett 264(1);110-6. PMID: 17020556

Stadtman01: Stadtman ER (2001). "The story of glutamine synthetase regulation." J Biol Chem 276(48);44357-64. PMID: 11585846

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

Alibhai94: Alibhai M, Villafranca JJ (1994). "Kinetic and mutagenic studies of the role of the active site residues Asp-50 and Glu-327 of Escherichia coli glutamine synthetase." Biochemistry 33(3);682-6. PMID: 7904829

Atkins92: Atkins WM, Villafranca JJ (1992). "Time-resolved fluorescence studies of tryptophan mutants of Escherichia coli glutamine synthetase: conformational analysis of intermediates and transition-state complexes." Protein Sci 1(3);342-55. PMID: 1363912

Atkins94: Atkins WM (1994). "Supramolecular self-assembly of Escherichia coli glutamine synthetase: effects of pressure and adenylylation state on dodecamer stacking." Biochemistry 33(50);14965-73. PMID: 7999752

Balakrishnan78: Balakrishnan MS, Villafranca JJ (1978). "Distance determinations between the metal ion sites of Escherichia coli glutamine synthetase by electron paramagnetic resonance using Cr(III)--nucleotides as paramagnetic substrate analogues." Biochemistry 17(17);3531-8. PMID: 28753

Bender77: Bender RA, Janssen KA, Resnick AD, Blumenberg M, Foor F, Magasanik B (1977). "Biochemical parameters of glutamine synthetase from Klebsiella aerogenes." J Bacteriol 129(2);1001-9. PMID: 14104

Bennett09: Bennett BD, Kimball EH, Gao M, Osterhout R, Van Dien SJ, Rabinowitz JD (2009). "Absolute metabolite concentrations and implied enzyme active site occupancy in Escherichia coli." Nat Chem Biol 5(8);593-9. PMID: 19561621

BRENDA14: BRENDA team (2014). Imported from BRENDA version existing on Aug 2014.

Bruggeman05: Bruggeman FJ, Boogerd FC, Westerhoff HV (2005). "The multifarious short-term regulation of ammonium assimilation of Escherichia coli: dissection using an in silico replica." FEBS J 272(8);1965-85. PMID: 15819889

Bywater75: Bywater RP, Carlisle CH, Jackson RB, Mackay AL, Timmins PA (1975). "Crystals of glutamine synthetase from Escherichia coli." J Mol Biol 91(3);293-300. PMID: 241853

Cervera88: Cervera J, Levine RL (1988). "Modulation of the hydrophobicity of glutamine synthetase by mixed-function oxidation." FASEB J 2(10);2591-5. PMID: 2898411

CohenKupiec93: Cohen-Kupiec R, Gurevitz M, Zilberstein A (1993). "Expression of glnA in the cyanobacterium Synechococcus sp. strain PCC 7942 is initiated from a single nif-like promoter under various nitrogen conditions." J Bacteriol 175(23);7727-31. PMID: 7902350

Colanduoni87: Colanduoni J, Nissan R, Villafranca JJ (1987). "Studies of the mechanism of glutamine synthetase utilizing pH-dependent behavior in catalysis and binding." J Biol Chem 262(7);3037-43. PMID: 2880845

Dabrowski94: Dabrowski MJ, Yanchunas J, Villafranca BC, Dietze EC, Schurke P, Atkins WM (1994). "Supramolecular self-assembly of glutamine synthetase: mutagenesis of a novel intermolecular metal binding site required for dodecamer stacking." Biochemistry 33(50);14957-64. PMID: 7999751

Dabrowski96: Dabrowski MJ, Dietze EC, Atkins WM (1996). "Engineering the aggregation properties of dodecameric glutamine synthetase: a single amino acid substitution controls 'salting out'." Protein Eng 9(3);291-8. PMID: 8736496

Dahlquist75: Dahlquist FW, Purich DL (1975). "Regulation of Escherichia coli glutamine synthetase. Evidence for the action of some feedback modifiers at the active site of the unadenylylated enzyme." Biochemistry 14(9);1980-9. PMID: 235974

DautryVarsat79: Dautry-Varsat A, Cohen GN, Stadtman ER (1979). "Some properties of Escherichia coli glutamine synthetase after limited proteolysis by subtilisin." J Biol Chem 254(8);3124-8. PMID: 34613

Dhalla94: Dhalla AM, Li B, Alibhai MF, Yost KJ, Hemmingsen JM, Atkins WM, Schineller J, Villafranca JJ (1994). "Regeneration of catalytic activity of glutamine synthetase mutants by chemical activation: exploration of the role of arginines 339 and 359 in activity." Protein Sci 3(3);476-81. PMID: 7912599

DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114

Farrington87: Farrington GK, Kumar A, Wedler FC (1987). "Design and synthesis of phosphonate inhibitors of glutamine synthetase." J Med Chem 1987;30(11);2062-7. PMID: 2889829

Fisher92: Fisher MT, Stadtman ER (1992). "Oxidative modification of Escherichia coli glutamine synthetase. Decreases in the thermodynamic stability of protein structure and specific changes in the active site conformation." J Biol Chem 267(3);1872-80. PMID: 1346137

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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
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