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: GDH shunt
|Superclasses:||Degradation/Utilization/Assimilation → Amino Acids Degradation → Proteinogenic Amino Acids Degradation → L-glutamate Degradation|
In this pathway L-glutamate is deaminated by an NAD-linked dehydrogenase, forming ammonia and 2-oxoglutarate, which is then fed to the TCA cycle I (prokaryotic). The pathway is found in microbes and plants.
The deamination of L-glutamate is a key reaction not only in the degradation of L-glutamate, but also in the degradation of several other amino acids. L-arginine, L-glutamine, L-histidine, and L-proline are all converted to L-glutamate during their catabolism [Schmidt88a].
The enzymes catalyzing the deamination of L-glutamate are the ubiquitous glutamate dehydrogenases (GDHs). GDHs catalyze a reversible reaction, and are involved in both the anabolic function of glutamate biosynthesis and the catabolic function of glutamate utilization, depending on the organism and the conditions. In some organisms, a single enzyme can catalyze both functions under different physiological conditions.
Most of the prokaryotic enzymes can use either NAD+ (EC 18.104.22.168) or NADP+ (EC 22.214.171.124) [Fisher73]. Although the NADP+-specific enzymes are capable of catalyzing a reversible reaction, they are believed to take part only in the anabolic reactions of glutamate biosynthesis, and thus included in L-glutamate biosynthesis III.
In yeast cells the amino group of glutamate and the amide group of glutamine are the source of nitrogen for all other macromolecules [Miller90a]. In order to provide ammonia for the synthesis of glutamine during growth on glutamate-yielding nitrogen sources, cells degrade glutamate into ammonia. The main pathway for Saccharomyces cerevisiae glutamate degradation is catalyzed by the NAD-dependent glutamate dehydrogenase encoded by GDH2 [Miller90a].
Plants have multiple forms of GDH enzymes. NAD(H)-specific enzymes are localized in the mitochondria, while NADP(H)-specific enzymes are associated with the chloroplasts [Srivastava87, Turano97]. Under severe carbon shortage conditions, plants convert L-glutamate to 2-oxoglutarate via this pathway, also known as the GDH shunt. 2-oxoglutarate then enters the TCA cycle I (prokaryotic) and carbon metabolism. Plant mutants lacking this capability have inhibited growth, especially under stress when carbon metabolism is in intense demand [MeloOliveira96]. The GDH shunt, together with the ammonia assimilation cycle (see superpathway of ammonia assimilation (plants)), play important role in the maintenance of carbon and nitrogen balance in plants. The GDH shunt is also thought to play a role in maintaining the internal glutamate concentration which is remarkably constant in Arabidopsis leaves.
some organisms posses a glutamate dehydrogenase that can utilize both NAD and NADP as a cofactor. these enzyme are described in the pathway L-glutamate degradation X.
Variants: GABA shunt, L-glutamate degradation II, L-glutamate degradation IV, L-glutamate degradation V (via hydroxyglutarate), L-glutamate degradation VI (to pyruvate), L-glutamate degradation VII (to butanoate), L-glutamate degradation VIII (to propanoate), L-glutamate degradation IX (via 4-aminobutanoate), L-glutamate degradation X
Unification Links: AraCyc:GLUTAMATE-DEG1-PWY
Martha Arnaud on Thu Aug 28, 2003:
This pathwas was formerly called glutamate degradation 1.
MeloOliveira96: Melo-Oliveira R, Oliveira IC, Coruzzi GM (1996). "Arabidopsis mutant analysis and gene regulation define a nonredundant role for glutamate dehydrogenase in nitrogen assimilation." Proc Natl Acad Sci U S A 93(10);4718-23. PMID: 8643469
Turano97: Turano FJ, Thakkar SS, Fang T, Weisemann JM (1997). "Characterization and expression of NAD(H)-dependent glutamate dehydrogenase genes in Arabidopsis." Plant Physiol 113(4);1329-41. PMID: 9112779
Aubert01: Aubert S, Bligny R, Douce R, Gout E, Ratcliffe RG, Roberts JK (2001). "Contribution of glutamate dehydrogenase to mitochondrial glutamate metabolism studied by (13)C and (31)P nuclear magnetic resonance." J Exp Bot 52(354);37-45. PMID: 11181711
Benachenhou91: Benachenhou N, Baldacci G (1991). "The gene for a halophilic glutamate dehydrogenase: sequence, transcription analysis and phylogenetic implications." Mol Gen Genet 230(3);345-52. PMID: 1766432
Bonete96: Bonete MJ, Perez-Pomares F, Ferrer J, Camacho ML (1996). "NAD-glutamate dehydrogenase from Halobacterium halobium: inhibition and activation by TCA intermediates and amino acids." Biochim Biophys Acta 1996;1289(1);14-24. PMID: 8605224
Ingoldsby05: Ingoldsby LM, Geoghegan KF, Hayden BM, Engel PC (2005). "The discovery of four distinct glutamate dehydrogenase genes in a strain of Halobacterium salinarum." Gene 349;237-44. PMID: 15780999
Johnson72: Johnson WM, Westlake DW (1972). "Purification and characterization of glutamic acid dehydrogenase and -ketoglutaric acid reductase from Peptococcus aerogenes." Can J Microbiol 1972;18(6);881-92. PMID: 4338318
Miller91b: Miller SM, Magasanik B (1991). "Role of the complex upstream region of the GDH2 gene in nitrogen regulation of the NAD-linked glutamate dehydrogenase in Saccharomyces cerevisiae." Mol Cell Biol 11(12);6229-47. PMID: 1682801
PerezPomares99: Perez-Pomares F, Ferrer J, Camacho M, Pire C, LLorca F, Bonete MJ (1999). "Amino acid residues involved in the catalytic mechanism of NAD-dependent glutamate dehydrogenase from Halobacterium salinarum." Biochim Biophys Acta 1999;1426(3);513-25. PMID: 10076069
Snedecor91: Snedecor B, Chu H, Chen E (1991). "Selection, expression, and nucleotide sequencing of the glutamate dehydrogenase gene of Peptostreptococcus asaccharolyticus." J Bacteriol 173(19);6162-7. PMID: 1917850
TerceLaforgue04: Terce-Laforgue T, Mack G, Hirel B (2004). "New insights towards the function of glutamate dehydrogenase revealed during source-sink transition of tobacco (Nicotiana tabacum) plants grown under different nitrogen regimes." Physiol Plant 120(2);220-228. PMID: 15032856
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