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Enzyme Nomenclature
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
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EC NUMBER 
COMMENTARY 
1.4.1.3
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RECOMMENDED NAME
GeneOntology No.
glutamate dehydrogenase [NAD(P)+]
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
L-glutamate + H2O + NAD(P)+ = 2-oxoglutarate + NH3 + NAD(P)H + H+
alternative order mechanism at pH 9.5; compulsory order mechanism at pH 8.8
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L-glutamate + H2O + NAD(P)+ = 2-oxoglutarate + NH3 + NAD(P)H + H+
compulsory order mechanism at pH 8.8
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L-glutamate + H2O + NAD(P)+ = 2-oxoglutarate + NH3 + NAD(P)H + H+
kinetic data suggest either a rapid-equilibrium random mechanism or a compulsory mechanism with binding sequence NH4+, NAD(P)H, 2-oxoglutarate
dogfish
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L-glutamate + H2O + NAD(P)+ = 2-oxoglutarate + NH3 + NAD(P)H + H+
mechanism
-
L-glutamate + H2O + NAD(P)+ = 2-oxoglutarate + NH3 + NAD(P)H + H+
-
-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
oxidation
-
-
-
-
redox reaction
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-
-
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reduction
-
-
-
-
reductive amination
-
-
-
-
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
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SYSTEMATIC NAME
IUBMB Comments
L-glutamate:NAD(P)+ oxidoreductase (deaminating)
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CAS REGISTRY NUMBER
COMMENTARY
9029-12-3
-
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
super-ovulating C57BL6/SJL hybrid mice, gene GlUD1
UniProt
enhanced ammonium concentrations and a reduced carbon supply induce the enzyme activity
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GWE1, a Gram-positive microaerophilic microorganism isolated from from the interior of a sterilization drying oven
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-
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391541, 391593, 391595, 391596, 391597, 391599, 391601, 391602, 391603, 391612, 391613, 391614, 391616, 391617, 391626, 391628, 391636, 655941, 671289, 689913, 725956, 742758
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
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
physiological function
-
influence of alcohol on leukocyte GLDH activity, its diagnostic value, influence on metabolism and cells toxicity is analysed. Examination is conducted in 238 alcoholics and in 244 healthy persons. A fast increase of leukocyte GLDH activity after break in alcohol consumption is found. After 24 hours, activity increases by 21.8% (median 31.6%), after seven days by 33% (median 52%), yet after a short interval since last alcohol intake (up to 48 hours), it increases by 32% (median 36%)
physiological function
the glutamate dehydrogenase catalyzes the reversible interconversion of glutamate to 2-oxoglutarate and ammonia using NADP(H) and NAD(H) as cofactors, thus interconnecting amino acid and carbohydrate metabolism. Mammalian GDH is allosterically regulated, with GTP and ADP being the main negative and positive modulators, respectively
physiological function
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the enzyme provides a pathway for ammonium assimilation, although the activity for ammonium is low
physiological function
-
the enzyme provides a pathway for ammonium assimilation
physiological function
-
allosteric activation and inhibition is important for enzyme regulation, overview
physiological function
enzyme is able to complement an Escherichia coli glutamate auxotroph lacking glutamate dehydrogenase
physiological function
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in a gene disruption strain of GDH, only threonine dehydrogenase activity is detected, indicating that activities toward Gln/Ala/Val/Cys are dependent on GDH. The disruption strain cannot grow in a medium in which growth is dependent on amino acid catabolism, GDH may be the only enzyme that can discharge the electrons (to NADP+/NAD+) released from amino acids in their oxidation to 2-oxoacids. In a medium containing excess pyruvate, the disprution strain displays normal growth, but higher degrees of amino acid catabolism are observed
physiological function
in transgenic Nicotiana tabacum the GDH protein accumulates in the mitochondria of mesophyll cells and in the mitochondria of the phloem companion cells. Overexpression induces major changes in carbon and nitrogen metabolite accumulation and a reduction in growth characterized by a decrease in the amount of sucrose, starch and glutamine in the leaves, and accompanied by an increase in the amount of nitrate and chlorophyl. There is an increase in the content of asparagine and a decrease in proline. Overexpressing the genes GDHA and GDHB individually or simultaneously induces a differential accumulation of glutamate and glutamine and a modification of the glutamate to glutamine ratio; in transgenic Nicotiana tabacum the GDH protein accumulates in the mitochondria of mesophyll cells and in the mitochondria of the phloem companion cells. Overexpression induces major changes in carbon and nitrogen metabolite accumulation and a reduction in growth characterized by a decrease in the amount of sucrose, starch and glutamine in the leaves, and accompanied by an increase in the amount of nitrate and chlorophyl. There is an increase in the content of asparagine and a decrease in proline. Overexpressing the genes GDHA and GDHB individually or simultaneously induces a differential accumulation of glutamate and glutamine and a modification of the glutamate to glutamine ratio
additional information
transgenic mice overexpressing the enzyme in brain have decreases in MAP2A labeling of dendrites and in synaptophysin labeling of presynaptic terminals, increasing in neuronal numbers and dendrite and presynaptic terminal labeling with advancing age, and show decreases in long-term potentiation of synaptic activity and in spine density in dendrites of CA1 neurons. Despite overexpression of Glud1 in all neurons of the central nervous system, the Tg mice suffer neuronal losses in select brain regions, e.g., the CA1 but not the CA3 region, dendrite structure and neuronal numbers in brains of transgenic mice, overview. The transgenic mice are significantly more resistant than wild-type mice to induction and duration of anesthesia produced by anesthetics that suppress Glu neurotransmission, phenotype, overview
additional information
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glutamate is bound to the active site of GdhB, the GdhB-Glu complex takes an open-like structure. No substrate is found in the active site of the GdhAGdhB-Leu complex, while six leucine molecules are found at the interfaces of three subunits
additional information
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transgenic mice overexpressing the enzyme in brain have decreases in MAP2A labeling of dendrites and in synaptophysin labeling of presynaptic terminals, increasing in neuronal numbers and dendrite and presynaptic terminal labeling with advancing age, and show decreases in long-term potentiation of synaptic activity and in spine density in dendrites of CA1 neurons. Despite overexpression of Glud1 in all neurons of the central nervous system, the Tg mice suffer neuronal losses in select brain regions, e.g., the CA1 but not the CA3 region, dendrite structure and neuronal numbers in brains of transgenic mice, overview. The transgenic mice are significantly more resistant than wild-type mice to induction and duration of anesthesia produced by anesthetics that suppress Glu neurotransmission, phenotype, overview
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
2-aminobutyrate + H2O + NADP+
2-oxobutyrate + NH3 + NADPH
-
3% of activity with L-glutamate
-
?
2-oxoglutarate + NH3 + NADPH + H+
L-glutamate + H2O + NADP+
-
-
-
?
L-glutamate + H2O + 2-azido-NAD+
2-oxoglutarate + NH3 + 2-azido-NADH
-
-
-
?
L-glutamate + H2O + N6-(2-aminoethyl)-NAD(P)+
2-oxoglutarate + NH3 + N6-(2-aminoethyl)-NAD(P)H
-
-
-
?
L-glutamate + H2O + N6-(2-hydroxy-3-trimethylammoniumpropyl)-NAD+
2-oxoglutarate + NH3 + N6-(2-hydroxy-3-trimethylammoniumpropyl)-NADH
-
-
-
?
L-glutamate + H2O + N6-(3-sulfonatopropyl)-NAD+
2-oxoglutarate + NH3 + N6-(2-sulfonatopropyl)-NADH
-
-
-
?
L-glutamate + H2O + polyethylenglycol-N6-(2-aminoethyl)-NAD(P)+
2-oxoglutarate + NH3 + polyethylenglycol-N6-(2-aminoethyl)-NAD(P)H
-
-
-
?
norvaline + H2O + NADP+
2-oxovalerate + NH3 + NADPH
-
activity is 20% of that observed in the presence of 2-oxoglutarate and L-glutamate
-
-
r
valine + H2O + NADP+
2-oxovalerate + NH3 + NADPH
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3% of activity with L-glutamate
-
?
2-oxoglutarate + NADH + NH3
L-glutamate + NAD+ + H2O
-
-
-
-
?
2-oxoglutarate + NADH + NH3
L-glutamate + NAD+ + H2O
-
no activity with NAD+ as cofactor
-
-
ir
2-oxoglutarate + NH3 + NADH
L-glutamate + H2O + NAD+
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specific activity in the presence of NADH is about 30% of that with NADPH
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r
alanine + H2O + NAD(P)+
pyruvate + NH3 + NAD(P)H
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very low activity
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-
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alanine + H2O + NAD(P)+
pyruvate + NH3 + NAD(P)H
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very low activity
-
-
-
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
-
highly specific for 2-oxoglutarate and glutamate
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r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
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enzyme for the main route for ammonia assimilation at low concentrations of ammonia
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r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
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-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
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very low activity with: leucine, alpha-aminobutyrate, valine, isoleucine and methionine
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r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
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rate of glutamate synthesis is several-fold higher than the rate for the reverse reaction
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r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
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-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
-
highly specific for 2-oxoglutarate and glutamate
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r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
Thermus thermophilus HB27 / ATCC BAA-163 / DSM 7039
-
-
-
-
?
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H + H+
-
-
-
-
?
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H + H+
-
-
-
-
?
L-glutamate + H2O + NAD+
2-oxoglutarate + NH3 + NADH + H+
-
-
-
r
L-glutamate + H2O + NAD+
2-oxoglutarate + NH3 + NADH + H+
-
-
-
-
r
L-glutamate + H2O + NADP+
2-oxoglutarate + NH3 + NADPH + H+
-
-
-
r
L-glutamate + H2O + NADP+
2-oxoglutarate + NH3 + NADPH + H+
-
-
-
-
?
L-glutamate + H2O + NADP+
2-oxoglutarate + NH3 + NADPH + H+
-
-
-
?
L-glutamate + H2O + NADP+
2-oxoglutarate + NH3 + NADPH + H+
-
-
-
-
r
L-glutamate + H2O + NADP+
2-oxoglutarate + NH3 + NADPH + H+
-
-
-
-
?
L-glutamate + H2O + NADP+
2-oxoglutarate + NH3 + NADPH + H+
-
-
-
?
L-glutamate + H2O + NADP+
2-oxoglutarate + NH3 + NADPH + H+
-
-
-
-
?
additional information
?
-
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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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-
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additional information
?
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the glutamate formation activity is 3fold higher than the glutamate deamination activity
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-
-
additional information
?
-
-
no activity in the amination reaction direction with NADH or NADPH, 2-oxoglutarate and ammonia
-
-
-
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
-
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+
-
-
-
-
?
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
-
-
-
L-glutamate + H2O + NAD+
2-oxoglutarate + NH3 + NADH + H+
P26443
-
-
-
r
L-glutamate + H2O + NAD+
2-oxoglutarate + NH3 + NADH + H+
-
-
-
-
r
L-glutamate + H2O + NADP+
2-oxoglutarate + NH3 + NADPH + H+
P26443
-
-
-
r
L-glutamate + H2O + NADP+
2-oxoglutarate + NH3 + NADPH + H+
-
-
-
-
r
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
NAD+
-
both NAD+ and NADP+ are utilized as cofactors. The inactive enzyme also binds cofactors
NADH
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reaction rate NADH/NADPH: 1.3 (GDH1); reaction rate NADH/NADPH: 4.5 (GDH2)
NADH
-
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391541, 654650, 655199, 655511, 655569, 655582, 656060, 656871, 673616, 675933, 712431, 725445, 725866
NADP+
-
both NAD+ and NADP+ are utilized as cofactors. The inactive enzyme also binds cofactors
NADPH
-
glutamate dehydrogenase 1, reaction rate NADH/NADPH: 1.3; glutamate dehydrogenase 2, reaction rate NADH/NADPH: 4.4
NADPH
-
NADPH/NADH ratio of reaction rate: 10/1, NAD+/NADH ratio of reaction rate: 5/1
NADPH
-
amination activity is 5fold higher with NADPH than that with NADH
additional information
-
2 soybean isoenzymes with different coenzyme specificities, glutamate dehydrogenase 1: active with NADH, NAD+, NADPH and NADP+, glutamate dehydrogenase 2: active with NADH, NAD+, NADPH but not NADP+
-
additional information
-
the enzyme can use both NAD+ and NADP+ as electron acceptors, displaying more affinity for NADP+ than for NAD+. No activity with NADH or NADPH
-
additional information
-
GDH is a dual-cofactor GDH, with activity that is greater with NAD+/NADH than with NADP+/NADPH
-
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. In the reductive amination direction, the rates of product formation are always greater for NADH oxidation than NADPH oxidation
-
additional information
cofactor specificity not mentioned
-
additional information
-
cofactor specificity not mentioned; cofactor specificity not mentioned
-
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
Mg2+
Ca2+
-
1 mM, 1.5fold activation of isozymes 1 and 3, 2.5fold activation of isozyme 2
Ca2+
-
addition of Ca2+ and Mg2+ also shows enhancement of enzyme activity. 3.5fold increase in activity at 10 mM CaCl2 or MgSO4
Ca2+
-
addition of Ca2+ and Mg2+ also shows enhancement of enzyme activity. 1.3fold increase in activity at 10 mM CaCl2 or MgSO4
Mg2+
-
addition of Ca2+ and Mg2+ also shows enhancement of enzyme activity. 3.5fold increase in activity at 10 mM CaCl2 or MgSO4
Mg2+
-
addition of Ca2+ and Mg2+ also shows enhancement of enzyme activity. 1.3fold increase in activity at 10 mM CaCl2 or MgSO4
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INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
8-azidoguanosine 5'-triphosphate
-
used for affinity photolabeling, 0.1 mM, 95% inhibition
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
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
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
L-aspartate
-
inhibition of NADPH linked reaction, activation of NAD(H) linked reaction
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
o-phthalaldehyde
-
0.1 mM, 98% inhibition after 5 min at 60°C, competitive vs. 2-oxoglutarate and NADH
oxalylglycine
-
competitive vs. 2-oxoglutarate, uncompetitive vs. NADPH, noncompetitive vs. NH4+
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
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
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
ATP
-
wild-type: inhibition at 0.1 mM and between 0.5-1.0 mM and above, activation at 1 mM, H454Y and S448P mutant enzyme: activation between 0.1-1 mM, inhibition above, R463A mutant enzyme: progressive inhibition between 0.01 and 10 mM
D-glutamate
-
10 mM, 57% inhibition of NADP+-linked activity, 30% inhibition of NADPH-linked activity
Glutarate
-
shows no affinity for N6-linked NAD+ but is biospecifically adsorbed to S6-linked NAD+ derivatives in the presence of its soluble kinetic-based enzyme capture ligand glutarate
GTP
-
GTP inhibition is attenuated to some extent by the proteolysis with TLCK-treated chymotrypsin
GTP
-
allosteric regulation, low inhibition of the deamination reaction and strong inhibition of the amination reaction
GTP
-
inhibition of wild-type enzyme and mutant enzymes r470H and N498S. No inhibition of mutant enzyme G456A. IC50 of wild-type enzyme is 0.00019 mM, IC50 of mutant enzyme G456A is 0.0028 mM, IC50 of mutant enzyme R470G is 0.00017 mM, IC50 of mutant enzyme N498S is 0.0002 mM
GTP
-
IC50 for wild-type GLUD1: 0.0122 mM, IC50 for mutant enzyme R443S: 0.0162 mM, IC50 for mutant enzyme M415L: 0.0147 mM, IC50 for mutant enzyme M370L: 0.0113 mM, IC50 for mutant enzyme S331T: 0.0108 mM
GTP
-
potent inhibitor. IC50 for wild-type enzyme is 0.00019 mM, IC50 for mutant enzyme G456A is 0.0028 mM. ADP renders the GLUD1-derived enzyme less sensitive to GTP inhibition; totally insensitive to, it becomes amenable to GTP inhibition in presence of ADP
GTP
-
efective inhibitor: activity below 10% of its full activity; GDH2 is resistent to GTP inhibition
GTP
-
allosteric regulation, low inhibition of the deamination reaction and strong inhibition of the amination reaction
NAD+
-
incubation with 0.1 mM for 60 min inhibits hGDH1 and hGDH2 by 75% and 70%, respectively, incubations for longer time periods up to 3 h, does not further increase the inhibition of hGDH isoenzymes, ADP-ribosylated hDGH isozymes are reactivated by Mg2+-dependent mitochondrial ADP-ribosylcysteine hydrolase
oxaloacetate
-
5 mM, 20-25% inhibition of NADH- and NAD+-dependent activities
palmitoyl-CoA
-
concentration-dependent inhibition, GDH1 is less sensitive to palmitoyl-CoA inhibition than GDH2
pyridoxal 5'-phosphate
dogfish
-
NAD+ and NADP+ protect from inactivation in the presence of sodium glutarate
pyridoxal 5'-phosphate
-
0.11 mM, approx. 30% inactivation after 10 min, 0.78 mM, 80% inactivation, inactivation is completely reversed by dialysis
additional information
-
complex inhibition pattern for ATP, GTP, NaCl, KCl, sodium acetate, NaI, and potassium nitrate of forward and reverse reaction at 5°C and 37°C
-
additional information
-
no inhibition or activation in the presence of ADP, GTP and leucine
-
additional information
-
complex inhibition pattern for ATP, GTP, NaCl, KCl, sodium acetate, NaI, and potassium nitrate of forward and reverse reaction at 5°C and 37°C
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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
-
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
-
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
-
ADP
-
ADP activation is almost abolished after treatment with TLCK-treated chymotrypsin
ADP
-
allosteric activator, addition of ADP or leucine to the single cofactor assay results in a marked activation of NADPH oxidation, about 1100% activation by ADP. Relative activation by ADP of GDH-catalyzed NAD+reduction is 36%, compared with 198% for NADP+ reduction
ADP
-
allosteric regulation, weak stimulation of the deamination reaction and strong activation of the amination reaction
ADP
-
1 mM, pH 8.0, 3fold activation of wild-type enzyme, no significant actication of Tyr187 mutant enzymes
ADP
-
in absence of GTP the isoenzyme GLUD2 assumes a conformational state associated with little catalytic activity, it remains amenable to full activation by ADP and/or L-Leu
ADP
the addition of FLAG tag to the C-terminus of GDH leaves the recombinant protein fivefold less sensitive to ADP activation
ADP
-
ADP induces an allosteric conformational change in GDH1, leading to a 2fold enhanced oxidative deamination
ADP
-
allosteric regulation, weak stimulation of the deamination reaction and strong activation of the amination reaction
AMP
-
1 mM, reaction velocity increases 15fold at saturating NAD+ and glutamate levels
AMP
-
activates NADH-linked glutamate synthesis, inhibits NADPH-linked activity; activation only in biosynthetic direction
ATP
-
allosteric regulation, weak stimulation of the deamination reaction and strong activation of the amination reaction
ATP
-
wild-type: activation at 1 mM, inhibition below and above, H454Y and S448P mutant enzymes: progressive increase in activity until 10 mM, inhibition above
ATP
-
activates in presence of 3 M NaCl or in absence of salts, slight inhibition in presence of 3 M KCl
ATP
-
allosteric regulation, weak stimulation of the deamination reaction and strong activation of the amination reaction
L-Leu
-
0.3-10 mM stimulates isoenzyme GLUD2 to a greater extent than isoenzyme GLUD1; 0.3-10 mM stimulates isoenzyme GLUD2 to a greater extent than isoenzyme GLUD1. In absence of GTP the isoenzyme GLUD2 assumes a conformational state associated with little catalytic activity, it remains amenable to full activation by ADP and/or L-Leu
L-leucine
-
allosteric activator, addition of ADP or leucine to the single cofactor assay results in a marked activation of NADPH oxidation, about 725% activation by L-leucine, respectively. Activation of NAD+ and NADP+ reduction by 40% and 135%, respectively
leucine
-
the enzyme is subject to allosteric activation by leucine invlving ARg134, and Asp185, structural mechanism, overview
leucine
with 10 mM the activity increases by 1.55fold after 240 min and by 1.24fold when the enzyme is preincubated with methylglyoxal
leucine
-
the enzyme is subject to allosteric activation by leucine, structural mechanism, overview
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.18
2-oxoglutarate
-
reductive amination, low-activity form of the enzyme
0.2
2-oxoglutarate
-
reductive amination, high-activity form of the enzyme
1.25
2-oxoglutarate
-
wild type isozyme GDH1, 50 mM triethanolamine pH 8.0, 100 mM ammonium acetate, 0.1 mM NADH, and 2 mM EDTA, pH 8.0 at 25°C
1.25
2-oxoglutarate
-
isozyme GDH1, in the presence of 1 mM ADP, in 50 mM triethanolamine, pH 8.0, 100 mM ammonium acetate, 0.1 mM NADH, and 2 mM EDTA, pH 8.0, at 25°C
1.27
2-oxoglutarate
-
mutant enzyme L415M/S443R/A456G, 50 mM triethanolamine pH 8.0, 100 mM ammonium acetate, 0.1 mM NADH, and 2 mM EDTA, pH 8.0 at 25°C
1.29
2-oxoglutarate
-
mutant enzyme M415L/R443S/G456A, 50 mM triethanolamine pH 8.0, 100 mM ammonium acetate, 0.1 mM NADH, and 2 mM EDTA, pH 8.0 at 25°C
1.39
2-oxoglutarate
-
wild type isozyme GDH2, 50 mM triethanolamine pH 8.0, 100 mM ammonium acetate, 0.1 mM NADH, and 2 mM EDTA, pH 8.0 at 25°C
1.39
2-oxoglutarate
-
isozyme GDH1, in the presence of 1 mM ADP, in 50 mM triethanolamine, pH 8.0, 100 mM ammonium acetate, 0.1 mM NADH, and 2 mM EDTA, pH 8.0, at 25°C
1.5
2-oxoglutarate
-
mutant enzyme R443S/G456A, in 50 mM triethanolamine buffer (pH 8.0), 2.6 mM EDTA, 1.4 mM NADP+, and 1 mM ADP
1.51
2-oxoglutarate
-
glutamate dehydrogenase 1, 0.1 mM NADH; glutamate dehydrogenase 1, 400 mM NH4+
1.54
2-oxoglutarate
-
isozyme 1, amination activity, cofactor NADPH
1.85
2-oxoglutarate
-
isozyme 2, amination activity, cofactor NADPH
2
2-oxoglutarate
-
wild type isozyme GDH1, in 50 mM triethanolamine buffer (pH 8.0), 2.6 mM EDTA, 1.4 mM NADP+, and 1 mM ADP
2.1
2-oxoglutarate
-
wild type isozyme GDH2, in 50 mM triethanolamine buffer (pH 8.0), 2.6 mM EDTA, 1.4 mM NADP+, and 1 mM ADP
3.5
2-oxoglutarate
-
in situ activity in 50 mM Tris-HCl buffer and 2 mM EDTA, pH 8, at 37°C
3.7
2-oxoglutarate
-
glutamate dehydrogenase 1, 0.2 mM NADH; glutamate dehydrogenase 2, 0.2 mM NADPH
3
L-glutamate
-
in situ activity in 50 mM Tris-HCl buffer and 2 mM EDTA, pH 8, at 37°C
3.65
L-glutamate
-
oxidative deamination, low-activity form of the enzyme
3.83
L-glutamate
-
oxidative deamination, high-activity form of the enzyme
10.7
L-glutamate
-
wild type isozyme GDH2, in 50 mM triethanolamine buffer (pH 8.0), 2.6 mM EDTA, 1.4 mM NADP+, and 1 mM ADP
10.8
L-glutamate
-
mutant enzyme R443S/G456A, in 50 mM triethanolamine buffer (pH 8.0), 2.6 mM EDTA, 1.4 mM NADP+, and 1 mM ADP
12.4
L-glutamate
-
wild type isozyme GDH1, in 50 mM triethanolamine buffer (pH 8.0), 2.6 mM EDTA, 1.4 mM NADP+, and 1 mM ADP
0.02
NAD+
-
in situ activity in 50 mM Tris-HCl buffer and 2 mM EDTA, pH 8, at 37°C
0.009
NADH
-
glutamate dehydrogenase 1, 5 mM 2-oxoglutarate; glutamate dehydrogenase 2, 5 mM 2-oxoglutarate
0.04
NADH
-
in situ activity in 50 mM Tris-HCl buffer and 2 mM EDTA, pH 8, at 37°C
0.075
NADH
-
mutant enzyme L415M/S443R/A456G, 50 mM triethanolamine pH 8.0, 100 mM ammonium acetate, 0.1 mM NADH, and 2 mM EDTA, pH 8.0 at 25°C
0.08
NADH
-
mutant enzyme M415L/R443S/G456A, 50 mM triethanolamine pH 8.0, 100 mM ammonium acetate, 0.1 mM NADH, and 2 mM EDTA, pH 8.0 at 25°C
0.081
NADH
-
wild type isozyme GDH1, 50 mM triethanolamine pH 8.0, 100 mM ammonium acetate, 0.1 mM NADH, and 2 mM EDTA, pH 8.0 at 25°C
0.081
NADH
-
isozyme GDH1, in the presence of 1 mM ADP, in 50 mM triethanolamine, pH 8.0, 100 mM ammonium acetate, 0.1 mM NADH, and 2 mM EDTA, pH 8.0, at 25°C
0.082
NADH
-
pH 8.0, 25°C, mutant enzyme Y187E; pH 8.0, 25°C, mutant enzyme Y187R
0.086
NADH
-
wild type isozyme GDH2, 50 mM triethanolamine pH 8.0, 100 mM ammonium acetate, 0.1 mM NADH, and 2 mM EDTA, pH 8.0 at 25°C
0.086
NADH
-
isozyme GDH2, in the presence of 1 mM ADP, in 50 mM triethanolamine, pH 8.0, 100 mM ammonium acetate, 0.1 mM NADH, and 2 mM EDTA, pH 8.0, at 25°C
0.035
NADP+
-
in situ activity in 50 mM Tris-HCl buffer and 2 mM EDTA, pH 8, at 37°C
0.028
NADPH
-
glutamate dehydrogenase 1, 10 mM 2-oxoglutarate; glutamate dehydrogenase 2, 10 mM 2-oxoglutarate
0.069
NADPH
-
glutamate dehydrogenase 1, 40 mM NH4+; glutamate dehydrogenase 2, 80 mM NH4+
10
NH3
-
in situ activity in 50 mM Tris-HCl buffer and 2 mM EDTA, pH 8, at 37°C
13.4
NH3
-
wild type isozyme GDH1, in 50 mM triethanolamine buffer (pH 8.0), 2.6 mM EDTA, 1.4 mM NADP+, and 1 mM ADP
17.1
NH3
-
wild type isozyme GDH2, in 50 mM triethanolamine buffer (pH 8.0), 2.6 mM EDTA, 1.4 mM NADP+, and 1 mM ADP
22.2
NH3
-
mutant enzyme R443S/G456A, in 50 mM triethanolamine buffer (pH 8.0), 2.6 mM EDTA, 1.4 mM NADP+, and 1 mM ADP
additional information
additional information
-
Km-values for 2-oxoglutaratefor mutant enzyme R443S, recombinant wild-type enzyme and wild-type enzyme from human liver
-
additional information
additional information
kinetic analysis in wild-type and transgenic overexpressing brain cell fractions, overview
-
additional information
additional information
-
lowering the pH of the buffer from pH 8.0 to pH 7.0 increases the Km for ammonia substantially, i.e. for hGDH1 from 12.8 mM to 57.5 mM, and for hGDH2: from 14.7 mM to 62.2 mM, thus essentially precluding reductive amination
-
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
17
2-oxoglutarate
-
hGDH1, mutant C323G; hGDH1, mutant C323L; hGDH2, mutant C323Y
19
2-oxoglutarate
-
hGDH1, mutant C323M; hGDH2, mutant C323M; hGDH2, mutant C323R
57
L-glutamate
-
pH 9.5, 25°C, mutant enzyme hGDH1D172Y; pH 9.5, 25°C, mutant enzyme hGDH2D172Y; pH 9.5, 25°C, mutant enzyme hGDH2G96Y
57
NAD+
-
pH 9.5, 25°C, mutant enzyme hGDH1D172Y; pH 9.5, 25°C, mutant enzyme hGDH2D172Y; pH 9.5, 25°C, mutant enzyme hGDH2G96Y
101
NADH
-
mutant enzyme M415L/R443S/G456A, 50 mM triethanolamine pH 8.0, 100 mM ammonium acetate, 0.1 mM NADH, and 2 mM EDTA, pH 8.0 at 25°C
104
NADH
-
wild type isozyme GDH1, 50 mM triethanolamine pH 8.0, 100 mM ammonium acetate, 0.1 mM NADH, and 2 mM EDTA, pH 8.0 at 25°C
104
NADH
-
isozyme GDH1, in the presence of 1 mM ADP, in 50 mM triethanolamine, pH 8.0, 100 mM ammonium acetate, 0.1 mM NADH, and 2 mM EDTA, pH 8.0, at 25°C
118
NADH
-
mutant enzyme L415M/S443R/A456G, 50 mM triethanolamine pH 8.0, 100 mM ammonium acetate, 0.1 mM NADH, and 2 mM EDTA, pH 8.0 at 25°C
130
NADH
-
wild type isozyme GDH2, 50 mM triethanolamine pH 8.0, 100 mM ammonium acetate, 0.1 mM NADH, and 2 mM EDTA, pH 8.0 at 25°C
130
NADH
-
isozyme GDH2, in the presence of 1 mM ADP, in 50 mM triethanolamine, pH 8.0, 100 mM ammonium acetate, 0.1 mM NADH, and 2 mM EDTA, pH 8.0, at 25°C