Information on EC 1.4.1.3 - glutamate dehydrogenase [NAD(P)+]

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The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea

EC NUMBER
COMMENTARY hide
1.4.1.3
-
RECOMMENDED NAME
GeneOntology No.
glutamate dehydrogenase [NAD(P)+]
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
L-glutamate + H2O + NAD(P)+ = 2-oxoglutarate + NH3 + NAD(P)H + H+
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
oxidation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
reductive amination
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Alanine, aspartate and glutamate metabolism
-
-
Arginine biosynthesis
-
-
D-Glutamine and D-glutamate metabolism
-
-
GABA shunt
-
-
glutamate and glutamine metabolism
-
-
L-glutamate biosynthesis II
-
-
L-glutamate degradation X
-
-
L-ornithine biosynthesis II
-
-
Metabolic pathways
-
-
Nitrogen metabolism
-
-
SYSTEMATIC NAME
IUBMB Comments
L-glutamate:NAD(P)+ oxidoreductase (deaminating)
-
CAS REGISTRY NUMBER
COMMENTARY hide
9029-12-3
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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-
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Manually annotated by BRENDA team
strain PCI 219
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Manually annotated by BRENDA team
strain PCI 219
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Manually annotated by BRENDA team
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-
-
Manually annotated by BRENDA team
dogfish
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
glutamate dehydrogenase 1 and 2
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
super-ovulating C57BL6/SJL hybrid mice, gene GlUD1
UniProt
Manually annotated by BRENDA team
Mus musculus C57BL6/SJL hybrid
super-ovulating C57BL6/SJL hybrid mice, gene GlUD1
UniProt
Manually annotated by BRENDA team
pea
-
-
Manually annotated by BRENDA team
sp. KOD1, hyperthermophilic archeon isolated from kodakara island, japan
-
-
Manually annotated by BRENDA team
ES4, hyperthermophilic archeon
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
strain DSM 158
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-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
enhanced ammonium concentrations and a reduced carbon supply induce the enzyme activity
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-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
tuna
-
-
Manually annotated by BRENDA team
GWE1, a Gram-positive microaerophilic microorganism isolated from from the interior of a sterilization drying oven
-
-
Manually annotated by BRENDA team
Richardson's ground squirrel
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-
Manually annotated by BRENDA team
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-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
-
while GDH in most mammals is encoded by a single GLUD1 gene, humans and other primates have acquired a GLUD2 gene with distinct tissue expression profile
metabolism
GDH1 is the protein partner for pyridoxamine 5'-phosphate-form of the mitochondrial branched chain aminotransferase (PMP-BCATm). Facilitating the recycling of BCATm to form metabolon, GDH1 acts as a catalytic machine
physiological function
additional information
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2-aminobutyrate + H2O + NADP+
2-oxobutyrate + NH3 + NADPH
show the reaction diagram
-
3% of activity with L-glutamate
-
?
2-oxoglutarate + NAD(P)H + NH3
L-glutamate + NAD(P)+ + H2O
show the reaction diagram
2-oxoglutarate + NADH + NH3
L-glutamate + NAD+ + H2O
show the reaction diagram
2-oxoglutarate + NADPH + NH3
L-glutamate + NADP+ + H2O
show the reaction diagram
2-oxoglutarate + NH3 + NADH
L-glutamate + H2O + NAD+
show the reaction diagram
2-oxoglutarate + NH3 + NADPH
L-glutamate + H2O + NADP+
show the reaction diagram
-
-
-
-
r
2-oxoglutarate + NH3 + NADPH + H+
L-glutamate + H2O + NADP+
show the reaction diagram
-
-
-
?
alanine + H2O + NAD(P)+
pyruvate + NH3 + NAD(P)H
show the reaction diagram
homocysteinesulfinate + H2O + NAD(P)+
?
show the reaction diagram
-
-
-
-
?
L-glutamate + H2O + 2-azido-NAD+
2-oxoglutarate + NH3 + 2-azido-NADH
show the reaction diagram
-
-
-
?
L-glutamate + H2O + N6-(2-aminoethyl)-NAD(P)+
2-oxoglutarate + NH3 + N6-(2-aminoethyl)-NAD(P)H
show the reaction diagram
-
-
-
?
L-glutamate + H2O + N6-(2-hydroxy-3-trimethylammoniumpropyl)-NAD+
2-oxoglutarate + NH3 + N6-(2-hydroxy-3-trimethylammoniumpropyl)-NADH
show the reaction diagram
-
-
-
?
L-glutamate + H2O + N6-(3-sulfonatopropyl)-NAD+
2-oxoglutarate + NH3 + N6-(2-sulfonatopropyl)-NADH
show the reaction diagram
-
-
-
?
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H + H+
show the reaction diagram
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NADPH + H+
show the reaction diagram
-
-
-
-
?
L-glutamate + H2O + NAD+
2-oxoglutarate + NH3 + NADH + H+
show the reaction diagram
L-glutamate + H2O + NADP+
2-oxoglutarate + NH3 + NADPH
show the reaction diagram
-
-
-
-
r
L-glutamate + H2O + NADP+
2-oxoglutarate + NH3 + NADPH + H+
show the reaction diagram
L-glutamate + H2O + polyethylenglycol-N6-(2-aminoethyl)-NAD(P)+
2-oxoglutarate + NH3 + polyethylenglycol-N6-(2-aminoethyl)-NAD(P)H
show the reaction diagram
-
-
-
?
L-glutamate + NAD+ + H2O
2-oxoglutarate + NADH + NH3
show the reaction diagram
L-glutamate + NADP+ + H2O
2-oxoglutarate + NADPH + NH3
show the reaction diagram
-
-
-
-
r
norvaline + H2O + NAD(P)+
2-oxopentanoate + NH3 + NAD(P)H
show the reaction diagram
norvaline + H2O + NADP+
2-oxovalerate + NH3 + NADPH
show the reaction diagram
-
activity is 20% of that observed in the presence of 2-oxoglutarate and L-glutamate
-
-
r
valine + H2O + NADP+
2-oxovalerate + NH3 + NADPH
show the reaction diagram
-
3% of activity with L-glutamate
-
?
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
-
enzyme for the main route for ammonia assimilation at low concentrations of ammonia
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H + H+
show the reaction diagram
-
-
-
-
?
L-glutamate + H2O + NAD+
2-oxoglutarate + NH3 + NADH + H+
show the reaction diagram
L-glutamate + H2O + NADP+
2-oxoglutarate + NH3 + NADPH + H+
show the reaction diagram
additional information
?
-
-
the similarity in relative activation when both cofactors are present, combined with consistently greater GDH product formation from equimolar NADH than with NADPH, does not support the idea that there is a preferential utilization of NADPH by bovine GDH
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-
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2-Azido-NAD+
-
-
NAD(P)H
-
-
additional information
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Ca2+
-
1 mM, 1.5fold activation of isozymes 1 and 3, 2.5fold activation of isozyme 2
KCl
-
3 mM, activates to 144% of control
NaCl
-
3 M, 67fold activation
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2-Azido-NAD+
-
0.1 mM, 60% inhibition after 3 min of photolabeling
2-oxobutyrate
-
-
2-oxoglutarate
2-oxovalerate
-
-
4-iodoacetamidosalicylic acid
-
-
5-Bromofuroate
-
-
5-Chlorofuroate
-
-
5-Nitrofuroate
-
-
8-Azidoguanosine 5'-triphosphate
-
used for affinity photolabeling, 0.1 mM, 95% inhibition
alanine
-
weak inhibition at pH 8.5, strong inhibition at pH 10.0
AlCl3
-
increase in sensitivity to aluminium as pH decreases, inhibitory effect is predominant below pH 7.0, no effect above pH 8.5. Completely inactivated enzyme contains 2 mol of aluminum per mol of subunit. Citrate, NaF, N-(2-hydroxyethyl) ethylenediaminetriacetic acid or EDTA efficiently protects against inactivation. Citrate and NaF release aluminum from the completely inactivated aluminum-enzyme complex and fully recover enzyme activity. Binding of aluminum induces a decrease in alpha helices and beta sheets and an increase in random coil
alpha-Ketoglutarate oxime
-
-
alpha-Monofluoroglutarate
-
-
alpha-Tetrazole
-
-
Aminooxyacetate
-
5 mM, weak inhibition of isozymes 1-3
AMP
-
inhibits only NADPH-linked activity
cardiolipin
-
-
Chloroquine
-
potent inhibitor of isozymes GDH1 and GDH2 at a dose-dependent manner, the inhibitory effect of chloroquine on GDH2 is abolished by the presence of ADP and L-leucine, whereas GTP does not change the sensitivity to chloroquine inhibition, shows a non-competitive inhibition against 2-oxoglutarate and an uncompetitive inhibition against NADH
citrate
-
10 mM, 60% inhibition of oxidative deamination
D-glutamate
diethylstilbestrol
-
-
Ditetrazole
-
-
fumarate
gamma-Tetrazole
-
-
GDP
strong allosteric inhibitor of GDH1 leading to a 90% reduction of activity. Addition of increasing concentrations of pyridoxamine 5'-phosphate-form of the mitochondrial branched chain aminotransferase (PMP-BCATm) leads to an increasing protection from GDP inhibition
glutamate
Glutarate
Glyoxal
histidine
-
weak inhibition at pH 8.5, strong inhibition at pH 10.0
imidodiacetic acid
-
-
Isophthalate
KCN
-
50 mM, strong inhibition of isozymes 1-3
L-aspartate
-
inhibition of NADPH linked reaction, activation of NAD(H) linked reaction
L-glutamate
-
-
lysine
-
weak inhibition at pH 8.5, strong inhibition at pH 10.0
m-Bromobenzoate
-
-
m-chlorobenzoate
-
-
m-Iodobenzoate
-
-
m-Nitrobenzoate
-
-
malate
-
5 mM, complete inhibition of NADH-linked activity
Methylacetimidate
-
100 mM, moderate inhibition of isozymes 1-3
methylglyoxal
with 1 mM methylglyoxal, GDH activity significantly decreases at 30 min of incubation, and markedly drops by 37% within 5 h compared to control
N-(N'-acetyl-4-sulfamoylphenyl)maleimide
-
-
NADH
-
high concentration
NADP+
-
-
NADPH
-
-
NH4+
-
-
Ni2+
-
1 mM, moderate inhibition of isozymes 1-3
norvaline
-
-
o-phenanthroline
-
5 mM, strong inhibition of isozymes 1-3
o-phthalaldehyde
-
0.1 mM, 98% inhibition after 5 min at 60C, competitive vs. 2-oxoglutarate and NADH
oxaloacetate
oxalylglycine
-
competitive vs. 2-oxoglutarate, uncompetitive vs. NADPH, noncompetitive vs. NH4+
Oxydiglycolic acid
-
-
p-chloromercuribenzoic acid
-
progressive decrease in enzyme activity of both isoenzymes, inhibition is not affected by addition of GTP or ADP
p-hydroxymercuribenzoate
-
5 mM, moderate inhibition of isozymes 1-3
palmitoyl-CoA
Phenylglyoxal
-
4 mM, 75% inhibition, uncompetitive vs. 2-oxoglutarate, noncompetitive vs. NADH
phosphate
-
pH 8.0-9.0: activation, pH 6.0-7.6: almost complete inhibition with 400 mM
phosphatidylserine
-
assumed to be a simple non-competitive inhibition
phosphoenolpyruvate
-
-
pyridoxal
-
NADH and NADPH protect from inactivation
pyridoxal 5'-phosphate
Sodium acetate
-
at 5C only
sodium dodecylsulfate
-
time-dependent irreversible inhibition, 0.2 mM, 37% inhibition, 0.15 mM, 50% inhibition after 30 min, in the presence of 2-oxoglutarate after 370 min
succinate
-
5 mM, complete inhibition of NADH-linked activity
sulfite
-
uncompetitive
Thiodiglycolic acid
-
-
Zn2+
-
1 mM, strong inhibition of isozymes 1-3
additional information
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2-mercaptoethanol
-
2fold activation
8-azidoguanosine 5'-diphosphate
-
used for affinity photolabeling
Chymotrypsin
-
0.2 mg/ml chymotrypsin cleaves glutamate dehydrogenase in such a fashion as to cause a rise in activity with NADP+ and NAD+ as coenzyme, over threefold activation in the NADP+ assay with TLCK-treated chymotrypsin, the distinguishing aspect with untreated chymotrypsin is that the activation is followed by a decrease in activity
-
glutathione
-
2fold activation
KCl
-
activates at 5C and 37C
L-aspartate
-
2fold activation of glutamate synthesis
L-His
-
activates in presence of 3 M NaCl, 3 M Kcl or in absence of salts
L-leucine
leucine
N6-(2-aminoethyl)-NAD+
-
-
N6-(2-aminoethyl)-NADP+
-
-
N6-(2-Hydroxy-3-trimethylammonium propyl)-NAD+
-
-
N6-(3-sulfonatopropyl)-NAD+
-
-
NaCl
-
activates at 37C only
phosphate
-
activator at pH 8.0-9.0, inhibitor at pH 6.0-7.6
PMP-BCATm
pyridoxamine 5'-phosphate-form of the mitochondrial branched chain aminotransferase (PMP-BCATm) accelerates the oxidative deamination reaction of GDH1in the presence of branched-chain amino acids (Leu, Ile, Val). Reductive amination reaction is not affected
-
Poly(ethylene glycol)-N6-(2-aminoethyl)-NAD+
-
-
-
Poly(ethylene glycol)-N6-(2-aminoethyl)-NADP+
-
-
-
Trypsin
-
limited trypsin proteolyis activates the purified enzyme 8fold if the peptide is absent from the assay mixture, the native enzyme is 3fold activated if the cleaved peptide is present, activation may therefore be induced by loss of the peptide from the subunit of the native enzyme
-
additional information
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.1 - 14
2-oxoglutarate
0.00294
alpha-ketoglutarate
-
-
0.25 - 23.8
glutamate
0.24 - 31
L-glutamate
0.291
N6-(2-aminoethyl)-NAD+
-
-
0.273
N6-(2-aminoethyl)-NADP+
-
-
0.148
N6-(2-hydroxy-2-trimethylammoniumpropyl)-NAD+
-
-
0.052
N6-(3-sulfonatopropyl)-NAD+
-
-
0.014 - 10.01
NAD+
0.000175 - 0.98
NADH
0.004 - 0.637
NADP+
0.006 - 0.78
NADPH
2.5 - 68
NH3
0.0424 - 160
NH4+
0.38 - 100
NH4Cl
49
norvaline
-
-
0.444
poly(ethyleneglycol)-N6-(2-aminoethyl)-NAD+
-
-
-
0.425
poly(ethyleneglycol)-N6-(2-aminoethyl)-NADP+
-
-
-
additional information
additional information
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
14 - 510
2-oxoglutarate
25 - 714
glutamate
2 - 121.2
L-glutamate
4 - 83
NAD+
77 - 374.5
NADH
102 - 399.6
NADP+
112 - 387.5
NADPH
43.8 - 168
NH4+
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
31
2-oxobutyrate
-
-
0.315 - 70
2-oxoglutarate
24.4
2-oxovalerate
-
-
0.005
8-Azidoguanosine 5'-triphosphate
-
-
4
ADP
-
-
6.2 - 23.2
alanine
0.76
ATP
-
inhibition of microtubules to membrane-bound liver enzyme
0.00036 - 0.0051
diethylstilbestrol
1.1 - 4.1
glutamate
0.07 - 0.09
Glutarate
0.000042 - 0.21
GTP
6.1
histidine
-
at pH 10.0
0.28
Isophthalate
-
-
6.3 - 80
L-glutamate
3.7 - 9.3
lysine
0.3
NAD+
-
kidney enzyme
0.011 - 0.016
NADH
0.24
NADP+
-
-
0.028
NADPH
-
-
2.9
NH4+
-
-
46 - 69
NH4Cl
78
norvaline
-
-
0.03 - 0.1
o-phthalaldehyde
0.36 - 0.9
oxalylglycine
0.000013 - 0.0002
palmitoyl-CoA
5 - 6
Phenylglyoxal
0.0009 - 0.061
phosphatidylserine
-
-