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MetaCyc Pathway: L-glutamate biosynthesis I
Inferred from experiment

Pathway diagram: L-glutamate 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.

Superclasses: BiosynthesisAmino Acids BiosynthesisProteinogenic Amino Acids BiosynthesisL-glutamate Biosynthesis

Some taxa known to possess this pathway include : Escherichia coli K-12 substr. MG1655

Expected Taxonomic Range: Archaea, Bacteria , Fungi, Viridiplantae

There are two pathways by which Escherichia coli synthesizes glutamate from ammonia. If complex sources of nitrogen are available, still other pathways (see below) become available and take over glutamate synthesis. The pathway shown here is one of the steps in one of the pathways by which glutamate is synthesized from ammonia. The other step ( L-glutamine biosynthesis I) in this pathway is the synthesis of glutamine from ammonia. Then in the step shown here that amido group is transferred to α-ketoglutarate yielding glutamate. Because glutamine biosynthesis utilizes glutamate and the reaction shown here yields 2 molecules of glutamate, these two reactions function as a cycle (see ammonia assimilation cycle III), each turn of which produces one molecule of glutamate at the expense of one molecule each of ammonia, ATP, NADPH, and α-ketoglutarate. The other ammonia-to-glutamate pathway, the one catalyzed by glutamate dehydrogenase ( L-glutamate biosynthesis III), also utilizes NADPH, and α-ketoglutarate, but it does not require ATP to drive the reaction. The Km for ammonia in this reaction is much higher than the Km for ammonia in ATP-driven cyclic pathway.

The two ammonia-to-glutamate pathways are regulated so as to operate under different environmental circumstances. The ATP-independent pathway functions when ammonia is abundant; the ATP-driven pathway functions when concentrations of ammonia are low. The ATP-independent pathway offers significant energy savings because when functioning, the ATP-driven pathway utilizes over 10 percent of the cell's total expenditure of ATP.

If complex sources of nitrogen are available, glutamate can be synthesized from arginine ( L-arginine degradation II (AST pathway)) or proline ( L-proline degradation) or from α-ketoglutarate by transamination of the amino group from arginine or aspartate.

The complexity of glutamate biosynthesis reflects the quantitatively central role that this amino acid plays in the metabolism of Escherichia coli. It is a major constituent of Escherichia coli's proteins and because it is a major nitrogen donor for other biosyntheses, about 80% of the cell's nitrogen flows through glutamate when Escherichia coli is growing on a medium containing ammonia as the total source of nitrogen.

Review: Reitzer, L. (2004) "Biosynthesis of Glutamate, Aspartate, Asparagine, L -Alanine, and D -Alanine." EcoSal [ECOSAL]

Superpathways: ammonia assimilation cycle III, L-glutamate and L-glutamine biosynthesis

Variants: L-arginine degradation I (arginase pathway), L-glutamate biosynthesis II, L-glutamate biosynthesis III, L-glutamate biosynthesis IV, L-glutamate biosynthesis V

Unification Links: EcoCyc:GLUTSYN-PWY

Created 31-Jul-1995 by Riley M, Marine Biological Laboratory
Revised 09-May-2006 by Ingraham JL, UC Davis


ECOSAL: EcoSal "Escherichia coli and Salmonella: Cellular and Molecular Biology." Online edition.

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

Arifuzzaman06: Arifuzzaman M, Maeda M, Itoh A, Nishikata K, Takita C, Saito R, Ara T, Nakahigashi K, Huang HC, Hirai A, Tsuzuki K, Nakamura S, Altaf-Ul-Amin M, Oshima T, Baba T, Yamamoto N, Kawamura T, Ioka-Nakamichi T, Kitagawa M, Tomita M, Kanaya S, Wada C, Mori H (2006). "Large-scale identification of protein-protein interaction of Escherichia coli K-12." Genome Res 16(5);686-91. PMID: 16606699

Berberich72: Berberich MA (1972). "A glutamate-dependent phenotype in E. coli K12: the result of two mutations." Biochem Biophys Res Commun 47(6);1498-503. PMID: 4402696

Bower83: Bower S, Zalkin H (1983). "Chemical modification and ligand binding studies with Escherichia coli glutamate synthase." Biochemistry 22(7);1613-20. PMID: 6342664

Butland05: Butland G, Peregrin-Alvarez JM, Li J, Yang W, Yang X, Canadien V, Starostine A, Richards D, Beattie B, Krogan N, Davey M, Parkinson J, Greenblatt J, Emili A (2005). "Interaction network containing conserved and essential protein complexes in Escherichia coli." Nature 433(7025);531-7. PMID: 15690043

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

Gaudet10: Gaudet P, Livstone M, Thomas P (2010). "Annotation inferences using phylogenetic trees." PMID: 19578431

Geary77: Geary LE, Meister A (1977). "On the mechanism of glutamine-dependent reductive amination of alpha-ketoglutarate catalyzed by glutamate synthase." J Biol Chem 1977;252(10);3501-8. PMID: 16906

GOA01: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

GOA01a: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

Goss01: Goss TJ, Perez-Matos A, Bender RA (2001). "Roles of glutamate synthase, gltBD, and gltF in nitrogen metabolism of Escherichia coli and Klebsiella aerogenes." J Bacteriol 183(22);6607-19. PMID: 11673431

Ishihama08: Ishihama Y, Schmidt T, Rappsilber J, Mann M, Hartl FU, Kerner MJ, Frishman D (2008). "Protein abundance profiling of the Escherichia coli cytosol." BMC Genomics 9;102. PMID: 18304323

Jongsareejit97: Jongsareejit B, Rahman RN, Fujiwara S, Imanaka T (1997). "Gene cloning, sequencing and enzymatic properties of glutamate synthase from the hyperthermophilic archaeon Pyrococcus sp. KOD1." Mol Gen Genet 254(6);635-42. PMID: 9202379

Lapointe75: Lapointe J, Delcuve G, Duplain L (1975). "Derepressed levels of glutamate synthase and glutamine synthetase in Escherichia coli mutants altered in glutamyl-transfer ribonucleic acid synthetase." J Bacteriol 123(3);843-50. PMID: 239924

Latendresse13: Latendresse M. (2013). "Computing Gibbs Free Energy of Compounds and Reactions in MetaCyc."

Lozoya80: Lozoya E, Sanchez-Pescador R, Covarrubias A, Vichido I, Bolivar F (1980). "Tight linkage of genes that encode the two glutamate synthase subunits of Escherichia coli K-12." J Bacteriol 144(2);616-21. PMID: 6107287

Mantsala76: Mantsala P, Zalkin H (1976). "Glutamate synthase. Properties of the glutamine-dependent activity." J Biol Chem 251(11);3294-9. PMID: 6449

Mantsala76a: Mantsala P, Zalkin H (1976). "Active subunits of Escherichia coli glutamate synthase." J Bacteriol 1976;126(1);539-41. PMID: 770440

Mantsala76b: Mantsala P, Zalkin H (1976). "Properties of apoglutamate synthase and comparison with glutamate dehydrogenase." J Biol Chem 251(11);3300-5. PMID: 6450

Metcalf90: Metcalf WW, Steed PM, Wanner BL (1990). "Identification of phosphate starvation-inducible genes in Escherichia coli K-12 by DNA sequence analysis of psi::lacZ(Mu d1) transcriptional fusions." J Bacteriol 172(6);3191-200. PMID: 2160940

Miller72: Miller RE, Stadtman ER (1972). "Glutamate synthase from Escherichia coli. An iron-sulfide flavoprotein." J Biol Chem 247(22);7407-19. PMID: 4565085

Showing only 20 references. To show more, press the button "Show all references".

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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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