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MetaCyc Pathway: L-glutamate biosynthesis III
Inferred from experiment

Enzyme View:

Pathway diagram: L-glutamate biosynthesis III

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, Saccharomyces cerevisiae

Expected Taxonomic Range: Archaea, Bacteria , Opisthokonta

This Pathway in Bacteria:

Escherichia coli K-12 can synthesize glutamate from ammonia in two pathways. In addition, if complex sources of nitrogen are available, other pathways (see below) become active and take over glutamate synthesis.

The pathway shown here synthesizes L-glutamate directly from ammonia, 2-oxoglutarate, and NADPH. The other is a cyclic pathway, which consists of two steps and requires ATP, and is described at ammonia assimilation cycle III).

Unlike the cyclic pathway, the pathway shown here does not require ATP to drive the reaction. The Km for ammonia of this reaction is much higher than that of the ATP-driven cyclic pathway.

Expression of the two ammonia-to-glutamate pathways is regulated so that they 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 over the ATP-driven pathway, as the latter uses over 10 percent of the cell's total expenditure of ATP when it is active [Helling02].

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 the amino acid plays in the metabolism of Escherichia coli. It is a major constituent of E. 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.

This Pathway in Yeast:

Like Escherichia coli K-12 yeast cells contain 2 pathways for the synthesis of glutamate. One of the pathways, shown here, is mediated by two isoforms of glutamate dehydrogenase, encoded by GDH1 and GDH3 [Moye85, Avendano97] (this pathway), while the second pathway is driven by the combined activities of glutamine synthetase and glutamate synthase, encoded by GLN1 and GLT1, respectively [Benjamin89, Filetici96] (see ammonia assimilation cycle III).

Studies of GDH1 and GDH3 regulation indicate that the cell uses these isoforms under different growth conditions [DeLuna01]. Expression of GDH3 is induced by ethanol and repressed by glucose, whereas GDH1 expression is high in either carbon source. Gdh1p uses α-ketoglutarate at a higher rate than Gdh3p. Thus, under fermentative growth conditions, Gdh1p drives glutamate biosynthesis, whereas in nonfermentable or limiting carbon sources, Gdh3p is the key isoform involved in balancing distribution of α-ketoglutarate to glutamate biosynthesis and energy metabolism.

Superpathways: L-glutamate and L-glutamine biosynthesis

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

Unification Links: EcoCyc:GLUTSYNIII-PWY

Created 15-Oct-2003 by Arnaud M, SRI International
Revised 09-May-2006 by Ingraham JL, UC Davis
Last-Curated 27-Mar-2007 by Shearer A, SRI International


Avendano97: Avendano A, Deluna A, Olivera H, Valenzuela L, Gonzalez A (1997). "GDH3 encodes a glutamate dehydrogenase isozyme, a previously unrecognized route for glutamate biosynthesis in Saccharomyces cerevisiae." J Bacteriol 179(17);5594-7. PMID: 9287019

Benjamin89: Benjamin PM, Wu JI, Mitchell AP, Magasanik B (1989). "Three regulatory systems control expression of glutamine synthetase in Saccharomyces cerevisiae at the level of transcription." Mol Gen Genet 217(2-3);370-7. PMID: 2570348

DeLuna01: DeLuna A, Avendano A, Riego L, Gonzalez A (2001). "NADP-glutamate dehydrogenase isoenzymes of Saccharomyces cerevisiae. Purification, kinetic properties, and physiological roles." J Biol Chem 276(47);43775-83. PMID: 11562373

Filetici96: Filetici P, Martegani MP, Valenzuela L, Gonzalez A, Ballario P (1996). "Sequence of the GLT1 gene from Saccharomyces cerevisiae reveals the domain structure of yeast glutamate synthase." Yeast 12(13);1359-66. PMID: 8923741

Helling02: Helling RB (2002). "Speed versus efficiency in microbial growth and the role of parallel pathways." J Bacteriol 184(4);1041-5. PMID: 11807064

Moye85: Moye WS, Amuro N, Rao JK, Zalkin H (1985). "Nucleotide sequence of yeast GDH1 encoding nicotinamide adenine dinucleotide phosphate-dependent glutamate dehydrogenase." J Biol Chem 260(14);8502-8. PMID: 2989290

Sakamoto75: Sakamoto N, Kotre AM, Savageau MA (1975). "Glutamate dehydrogenase from Escherichia coli: purification and properties." J Bacteriol 1975;124(2);775-83. PMID: 241744

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

Becerril85: Becerril B, Valle F, Merino E, Riba L, Bolivar F (1985). "Repetitive extragenic palindromic (REP) sequences in the Escherichia coli gdhA gene." Gene 37(1-3);53-62. PMID: 3902576

Blumenthal73: Blumenthal KM, Smith EL (1973). "Nicotinamide adenine dinucleotide phosphate-specific glutamate dehydrogenase of Neurospora. I. Isolation, subunits, amino acid composition, sulfhydryl groups, and identification of a lysine residue reactive with pyridoxal phosphate and N-ethylmaleimide." J Biol Chem 248(17);6002-8. PMID: 4146914

Bonete90: Bonete MJ, Camacho ML, Cadenas E (1990). "Analysis of the kinetic mechanism of halophilic NADP-dependent glutamate dehydrogenase." Biochim Biophys Acta 1990;1041(3);305-10. PMID: 1980084

Dean94: Dean JL, Wang XG, Teller JK, Waugh ML, Britton KL, Baker PJ, Stillman TJ, Martin SR, Rice DW, Engel PC (1994). "The catalytic role of aspartate in the active site of glutamate dehydrogenase." Biochem J 301 ( Pt 1);13-6. PMID: 8037659

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

GarciaGalan13: Garcia-Galan C, Barbosa O, Fernandez-Lafuente R (2013). "Stabilization of the hexameric glutamate dehydrogenase from Escherichia coli by cations and polyethyleneimine." Enzyme Microb Technol 52(4-5);211-7. PMID: 23540921

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."

Helling90: Helling RB (1990). "The glutamate dehydrogenase structural gene of Escherichia coli." Mol Gen Genet 223(3);508-12. PMID: 2270089

Helling94: Helling RB (1994). "Why does Escherichia coli have two primary pathways for synthesis of glutamate?." J Bacteriol 1994;176(15);4664-8. PMID: 7913929

Helling98: Helling RB (1998). "Pathway choice in glutamate synthesis in Escherichia coli." J Bacteriol 180(17);4571-5. PMID: 9721297

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

Jones93: Jones KM, McPherson MJ, Baron AJ, Mattaj IW, Riordan CL, Wootton JC (1993). "The gdhA1 point mutation in Escherichia coli K12 CLR207 alters a key lysine residue of glutamate dehydrogenase." Mol Gen Genet 240(2);286-9. PMID: 8355660

Kim90: Kim SY, McLaggan D, Epstein W (1990). "The gdhA gene is located at 38.6 minutes on the Escherichia coli map." J Bacteriol 172(10);6127-8. PMID: 2170342

Korber93: Korber FC, Rizkallah PJ, Attwood TK, Wootton JC, McPherson MJ, North AC, Geddes AJ, Abeysinghe IS, Baker PJ, Dean JL (1993). "Crystallization of the NADP(+)-dependent glutamate dehydrogenase from Escherichia coli." J Mol Biol 234(4);1270-3. PMID: 8263929

Kumar10: Kumar R, Shimizu K (2010). "Metabolic regulation of Escherichia coli and its gdhA, glnL, gltB, D mutants under different carbon and nitrogen limitations in the continuous culture." Microb Cell Fact 9;8. PMID: 20105320

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

Li14: Li H, Liao JC (2014). "Development of an NADPH-dependent homophenylalanine dehydrogenase by protein engineering." ACS Synth Biol 3(1);13-20. PMID: 24053171

Liang15: Liang B, Zhang S, Lang Q, Song J, Han L, Liu A (2015). "Amperometric L-glutamate biosensor based on bacterial cell-surface displayed glutamate dehydrogenase." Anal Chim Acta 884;83-9. PMID: 26073813

LopezCampistrou05: Lopez-Campistrous A, Semchuk P, Burke L, Palmer-Stone T, Brokx SJ, Broderick G, Bottorff D, Bolch S, Weiner JH, Ellison MJ (2005). "Localization, annotation, and comparison of the Escherichia coli K-12 proteome under two states of growth." Mol Cell Proteomics 4(8);1205-9. PMID: 15911532

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
Page generated by Pathway Tools version 19.5 (software by SRI International) on Tue May 3, 2016, biocyc14.