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:||Biosynthesis → Amino Acids Biosynthesis → Individual Amino Acids Biosynthesis → Glutamate Biosynthesis|
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 (arginine degradation II (AST pathway)) or proline (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: glutamate and glutamine biosynthesis
Unification Links: EcoCyc:GLUTSYNIII-PWY
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
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
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
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
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
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
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
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