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Enzyme Nomenclature
Information on EC 4.1.1.15 - glutamate decarboxylase
Word Map on EC 4.1.1.15
- 4.1.1.15
- neuron
-
gabaergic
- diabetes
-
gamma-aminobutyric
- autoimmune
-
autoantibody
- cortex
- nucleus
-
neurotransmitter
- islet
-
synaptic
- mellitus
- hippocampus
- striatum
-
interneurons
-
axon
-
autoantigens
- choline
-
ventral
-
dorsal
-
insulin-dependent
-
synapses
-
cholinergic
-
excitatory
-
medial
-
parvalbumin
-
glutamatergic
-
postsynaptic
-
beta-cell
-
substantia
-
neurochemical
-
afferent
-
boutons
- gaba-t
-
rostral
-
chat
-
calbindin
-
somata
-
c-peptide
- colliculus
-
autoreactive
-
globus
-
calretinin
-
preoptic
- pallidus
- bicuculline
- pharmacology
- medicine
- muscimol
-
subthalamic
- analysis
- food industry
- gaba-transaminase
- synthesis
-
subnuclei
- diagnostics
- nutrition
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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
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EC NUMBER 
COMMENTARY 
4.1.1.15
-
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RECOMMENDED NAME
GeneOntology No.
glutamate decarboxylase
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
L-glutamate = 4-aminobutanoate + CO2
-
-
-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
decarboxylation
decarboxylation
-
-
-
-
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
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SYSTEMATIC NAME
IUBMB Comments
L-glutamate 1-carboxy-lyase (4-aminobutanoate-forming)
A pyridoxal-phosphate protein. The brain enzyme also acts on L-cysteate, 3-sulfino-L-alanine and L-aspartate.
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CAS REGISTRY NUMBER
COMMENTARY
9024-58-2
-
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
isolated from traditional Korean fermented food kimchi, gene gad
UniProt
-
-
-
-
3980, 654404, 655357, 656303, 656337, 656454, 656697, 682084, 691484, 692644, 697040, 697049, 697424, 697426, 697564, 697572, 697841, 698535, 699151, 699668, 699674, 700597, 700978, 703503
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alcohol dependent and non-alcohol dependent individuals of Irish origin, male and female
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-
isolated from traditional Korean fermented food kimchi, gene gad
UniProt
strain LO28, having a GAD system consisting of enzyme plus a glutamate/gamma-aminobutyrate antiporter. Enzyme/transporter pair GAD2/T2 is primarily responsible for surviving severe acid challenge, enzyme GAD1 plays a major role in growth at mildly acidic pH-values
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genes gadD1, gadD2, and gadD3 encode glutamate decarboxylases
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strain LO28, having a GAD system consisting of enzyme plus a glutamate/gamma-aminobutyrate antiporter. Enzyme/transporter pair GAD2/T2 is primarily responsible for surviving severe acid challenge, enzyme GAD1 plays a major role in growth at mildly acidic pH-values
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-
-
3983, 3984, 3992, 3995, 677575, 678980, 695988, 697040, 697572, 700429, 700956, 705287, 705316, 705319
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male C57BI/6 mice, genes GAD65 and GAD67 encoding the 65-kDa and the 67-kDa isozymes of glutamic acid decarboxylase
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
malfunction
metabolism
-
the 4-aminobutanoate shunt pathway possesses three enzymes encoded by genes gad, gabT, and gabD. Among the three, GAD is the key cytosolic-located enzyme which catalyzes the irreversible decarboxylation of L-glutamate to produce 4-aminobutanoate
physiological function
additional information
evolution
-
clustal X-generated dendrogram of bacterial glutamate decarboxylases, overview
evolution
clustal X-generated dendrogram of bacterial glutamate decarboxylases, overview; clustal X-generated dendrogram of bacterial glutamate decarboxylases, overview
evolution
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clustal X-generated dendrogram of bacterial glutamate decarboxylases, overview
evolution
-
clustal X-generated dendrogram of bacterial glutamate decarboxylases, overview
-
evolution
-
clustal X-generated dendrogram of bacterial glutamate decarboxylases, overview
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malfunction
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the GAD65 null mutation affects neural activities during fear memory extinction and examined local field potentials from the lateral amygdala, the CA1 area of the hippocampus, and the infralimbic area of the prefrontal cortex during this process in Gad65deficient mice
malfunction
-
GAD65 knockout mice show a diminished response to propofol, but not ketamine, indicating that GAD65-mediated 4-aminobutanoate synthesis plays an important role in hypnotic and immobilizing actions of propofol
malfunction
-
survival of the gadB mutant after 60 min in the presence of 0.045 mg/ml nisin powder is approximately 5fold less than that of the parental strain
malfunction
-
the DELTAgadD1 mutant is impaired in its ability to tolerate exposure to both sublethal and lethal levels of the lantibiotic nisin
malfunction
-
survival of the gadB mutant after 60 min in the presence of 0.045 mg/ml nisin powder is approximately 5fold less than that of the parental strain
-
malfunction
-
the DELTAgadD1 mutant is impaired in its ability to tolerate exposure to both sublethal and lethal levels of the lantibiotic nisin
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physiological function
-
the GAD acid resistance system does not play any role in the survival of Listeria monocytogenes at a low pH
physiological function
-
the GAD acid resistance system does not play any role in the survival of Salmonella enterica at a low pH
physiological function
-
GAD65-mediated 4-aminobutanoate synthesis plays relatively small but significant roles in nociceptive processing via supraspinal mechanisms
physiological function
-
possession of the gadD1 gene correlates with a higher degree of tolerance to nisin
physiological function
-
possession of the gadD1 gene correlates with a higher degree of tolerance to nisin
physiological function
-
GAD1 plays an important role in responses to abiotic factors and hormone treatments
physiological function
GAD plays a role in hypocotyl and stem development in pine
physiological function
-
the glutamate decarboxylase system is important for the acid resistance of Listeria monocytogenes. Cells accumulate intracellular 4-aminobutanoate as a standard response against acid in any medium. The GADi system is activated at milder pH values of pH 4.5 to pH 5.0 than theGADe system, pH 4.0 to pH 4.5, suggesting that GADi is the more responsive of the two and the first line of defense against acid. Model for the function of the GAD system under severe acid conditions below pH 4.5
physiological function
-
the glutamate-dependent acid resistance (GDAR) system is by far the most potent acid resistance system in commensal and pathogenic Escherichia coli and requires the activity of intracellular glutamate decarboxylase GadB performing a proton-consuming decarboxylation reaction and the cognate antiporter GadC, which performs the glutamate/in/gamma-aminobutyrate/out electrogenic antiport, overview
physiological function
-
the glutamate-dependent acid resistance (GDAR) system is by far the most potent acid resistance system in commensal and pathogenic Listeria monocytogenes and requires the activity of intracellular glutamate decarboxylase GadB performing a proton-consuming decarboxylation reaction and the cognate antiporter GadC, which performs the glutamate/in/gamma-aminobutyrate/out electrogenic antiport, overview
physiological function
-
possession of the gadD1 gene correlates with a higher degree of tolerance to nisin
-
physiological function
-
possession of the gadD1 gene correlates with a higher degree of tolerance to nisin; the glutamate decarboxylase system is important for the acid resistance of Listeria monocytogenes. Cells accumulate intracellular 4-aminobutanoate as a standard response against acid in any medium. The GADi system is activated at milder pH values of pH 4.5 to pH 5.0 than theGADe system, pH 4.0 to pH 4.5, suggesting that GADi is the more responsive of the two and the first line of defense against acid. Model for the function of the GAD system under severe acid conditions below pH 4.5
-
additional information
binding of pyridoxal 5'-phosphate as well as to the active site residues Thr215 and Asp246 that promote decarboxylation
additional information
residues T215 and D246 are involved in catalysis
additional information
-
important role of C-terminal region in the pH-dependent regulation of enzyme activity. Enzyme molecular homology modeling
additional information
the N-terminal fourteen residues (1-14) of homohexameric GadB forms a triple-helix bundle interdomain at acidic pH and contributes to the thermostability of GadB as the pH shifts from pH 7.6 to pH 4.6
additional information
-
at neutral pH the enzyme is in a compact conformation with access to the active site precluded by steric hindrance of some structural elements, a sequence of events lead to the conversion of GadB from the inactive into the active form and vice versa, structural determinants responsible for pH-dependent intracellular activation of GadB, overview. In its inactive form GadB has (i) the N-terminal residues 1-14 of each subunit mainly involved in dimerization and hexamerization, (ii) the C-terminal residues 452-466 ordered and protruding into the active site (with residues His465 and Thr466), like a plug, thus occupying the binding site of the physiological substrate glutamate, (iii) the beta-hairpin 300-313 contacting the C-terminal tail of the other subunit in the dimer as to hold it in place, structure comparisons, overview
additional information
absence of a His residue near the C-terminus in Lactobacillus brevis GadB homologue LVIS_0079
additional information
absence of a His residue near the C-terminus in Lactobacillus brevis GadB homologue LVIS_0079
additional information
-
residues T215 and D246 are involved in catalysis
-
additional information
-
absence of a His residue near the C-terminus in Lactobacillus brevis GadB homologue LVIS_0079
-
additional information
-
binding of pyridoxal 5'-phosphate as well as to the active site residues Thr215 and Asp246 that promote decarboxylation; important role of C-terminal region in the pH-dependent regulation of enzyme activity. Enzyme molecular homology modeling
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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
L-Asp
?
-
Phe or 6-azauracil decrease specificity for L-Glu and increase specificity to L-Asp
-
-
-
L-Glu
4-Aminobutanoate + CO2
-
rate-limiting enzyme involved in the synthesis of gamma-aminobutyric acid
-
-
?
L-Glu
4-Aminobutanoate + CO2
-
6-azauracil or Phe decrease specificity for L-Glu and increased specificity to L-Asp
-
-
-
L-Glu
?
-
the enzyme is under the control of the asexual developmental cycle
-
-
-
L-Glu
?
-
production of 4-aminobutanoate, which is the major inhibitory neurotransmitter in the mammalian brain
-
-
-
L-glutamate
4-aminobutanoate + CO2
-
GAD67 is a rate-limiting enzyme for GABA synthesis, GAD65 is important for the local control of GABA synthesis at the synaptic sites, whereas GAD67 is responsible for maintaining GABA baseline levels for both neurotransmitter and metabolite
-
-
?
L-glutamate
4-aminobutanoate + CO2
-
GAD is the rate-limiting enzyme for GABA biosynthesis
-
-
?
L-glutamate
4-aminobutanoate + CO2
-
GAD is the rate-limiting enzyme for GABA biosynthesis
-
-
?
L-glutamate
4-aminobutanoate + CO2
-
-
-
-
?
L-glutamate
4-aminobutanoate + CO2
-
the alpha-carboxyl group, leaving as CO2, is thus replaced by a cytoplasmic proton, yielding 4-aminobutanoate
-
-
?
L-glutamate
4-aminobutanoate + CO2
-
the reaction does not occur, when L-glutamate concentration is more than 4fold that of L-glutamine
-
-
?
L-glutamate
4-aminobutanoate + CO2
-
-
-
-
?
L-glutamate
4-aminobutanoate + CO2
-
GAD is the key enzyme of GABA synthesis, alterations of GABAergic neurotransmission are assumed to play a crucial role in the pathophysiology of mood disorders, overview. Increased relative density of GAD-immunoreactive neuropil, suggests the diathesis of GABAergic system specific for depressed suicidal patients
-
-
?
L-glutamate
4-aminobutanoate + CO2
GAD is the rate-limiting enzyme in controlling GABA synthesis, GABA is synthesized by GAD67 is used for the other functions such as trophic factor for neuronal development or energy source. GAD67 is constitutively active and is responsible for the basal GABA production
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-
?
L-glutamate
4-aminobutanoate + CO2
GAD is the rate-limiting enzyme in controlling GABA synthesis, GAD65 is transiently activated in response to the extra demand of GABA in neurotransmission
-
-
?
L-glutamate
4-aminobutanoate + CO2
-
GAD is the rate-limiting enzyme in neurotransmitter gamma-aminobutyric acid, GABA, biosynthesis
-
-
?
L-glutamate
4-aminobutanoate + CO2
-
human glutamic acid decarboxylase 65 is a key autoantigen in type 1 diabetes
-
-
?
L-glutamate
4-aminobutanoate + CO2
-
the isozymes are involved in autoimmune response and diseases, such as diabetes mellitus and Graves' disease, overview. Correlations between anti-GAD autoantibodies and diseases, overview
-
-
?
L-glutamate
4-aminobutanoate + CO2
the alpha-carboxyl group, leaving as CO2, is replaced by a cytoplasmic proton, yielding 4-aminobutanoate
-
-
?
L-glutamate
4-aminobutanoate + CO2
the alpha-carboxyl group, leaving as CO2, is thus replaced by a cytoplasmic proton, yielding 4-aminobutanoate
-
-
?
L-glutamate
4-aminobutanoate + CO2
the alpha-carboxyl group, leaving as CO2, is thus replaced by a cytoplasmic proton, yielding 4-aminobutanoate
-
-
?
L-glutamate
4-aminobutanoate + CO2
the alpha-carboxyl group, leaving as CO2, is replaced by a cytoplasmic proton, yielding 4-aminobutanoate
-
-
?
L-glutamate
4-aminobutanoate + CO2
-
the alpha-carboxyl group, leaving as CO2, is replaced by a cytoplasmic proton, yielding 4-aminobutanoate
-
-
?
L-glutamate
4-aminobutanoate + CO2
-
-
-
-
?
L-glutamate
4-aminobutanoate + CO2
-
GAD is the rate-limiting enzyme in controlling GABA synthesis, GABA is synthesized by GAD67 is used for the other functions such as trophic factor for neuronal development or energy source. GAD67 is constitutively active and is responsible for the basal GABA production while GAD65 is transiently activated in response to the extra demand of GABA in neurotransmission
-
-
?
L-glutamate
4-aminobutanoate + CO2
-
GAD is the rate-limiting enzyme in neurotransmitter gamma-aminobutyric acid, GABA, biosynthesis
-
-
?
L-glutamate
4-aminobutanoate + CO2
-
GAD65-mediated GABA synthesis is critical for the consolidation of stimulus-specific fear memory. This function appears to involve a modulation of neural activity patterns in the amygdalo-hippocampal pathway as indicated by a reduction in theta frequency synchronization between the amygdala and hippocampus of Gad65-/- mice during the expression of generalized fear memory
-
-
?
L-glutamate
4-aminobutanoate + CO2
-
GAD67 is the rate-limiting enzyme of GABA biosynthesis
-
-
?
L-glutamate
4-aminobutanoate + CO2
-
nicotine, by activating nAChRs located on cortical or hippocampal GABAergic interneurons, can up-regulate GAD67 expression via an epigenetic mechanism
-
-
?
L-glutamate
4-aminobutanoate + CO2
-
-
-
-
?
L-glutamate
4-aminobutanoate + CO2
-
GAD is the rate-limiting enzyme in controlling GABA synthesis, GABA is synthesized by GAD67 is used for the other functions such as trophic factor for neuronal development or energy source. GAD67 is constitutively active and is responsible for the basal GABA production while GAD65 is transiently activated in response to the extra demand of GABA in neurotransmission
-
-
?
L-glutamate
4-aminobutanoate + CO2
-
GAD is the rate-limiting enzyme in neurotransmitter gamma-aminobutyric acid, GABA, biosynthesis
-
-
?
L-glutamate
4-aminobutanoate + CO2
-
glutamate decarboxylase is the rate-limiting enzyme in the synthesis of gamma-aminobutyric acid, the most important inhibitory neurotransmitter in central nervous system
-
-
?
L-glutamate
4-aminobutanoate + CO2
-
the enzyme activity is higher in hippocampus of old rats compared to young rats
-
-
?
L-glutamate
4-aminobutanoate + CO2
irreversible alpha-decarboxylation of L-glutamate, the enzyme is highly specific for L-glutamate, no activity with D-glutamate and 23 other amino acids, overview
-
-
ir
additional information
?
-
-
the reduction of GAD67 immunoreactive neurons in the hippocampal CA1 region may be closely related to highly susceptibility to memory loss in old aged dogs
-
-
-
additional information
?
-
-
GadB together with the antiporter gadC constitutes the gad acid resistance system, which confers the ability for bacterial survival for at least 2 h in a strongly acidic environment
-
-
-
additional information
?
-
-
of the two homolous forms of glutamic acid decarboxylase, GAD65 and GAD67, only GAD65 is a common target of autoimmunity
-
-
-
additional information
?
-
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isoform GAD65 undergoes a side reaction yielding pyridoxamine 5’-phosphate, succinic semialdehyde and inactive apo enzyme
-
-
-
additional information
?
-
-
association of the two GAD isoforms in Irish individuals with Alzheimer's disease and relevant alcohol-related traits in the irish affected Sib pair study of alcohol dependence, overview. Significant association of GAD1 with initial sensitivity and age at onset of Alzheimer's disease
-
-
-
additional information
?
-
-
calpains inhibit the GAD cleavage in vivo, overview
-
-
-
additional information
?
-
-
enhanced anti-GAD antibodies are associated with several neurological diseases, possibly also the indiopathic Opsoclonus-myoclonus-ataxia syndrome, OMS. The anti-GAD antibodies might act via impairing GABAergic transmission in specific brainstem and cerebellar circuits, overview
-
-
-
additional information
?
-
-
GAD1 might be the susceptibility gene or another one being the susceptibility gene for autism, located on chromosome 2q31
-
-
-
additional information
?
-
GAD65 plays an essential role in neurotransmission, and is a typical autoantigen in several human autoimmune diseases, such as insulin-dependent diabetes mellitus, IDDM and Stiffman-Person syndrome, SPS. Posttranslational regulation of the enzyme in brain, overview
-
-
-
additional information
?
-
GAD65 plays an essential role in neurotransmission, and is a typical autoantigen in several human autoimmune diseases, such as insulin-dependent diabetes mellitus, IDDM and Stiffman-Person syndrome, SPS. Posttranslational regulation of the enzyme in brain, overview
-
-
-
additional information
?
-
-
high levels of autoantibodies to glutamic acid decarboxylase are associated with the stiff-person syndrome and type 1 diabetes mellitus and other pathologies, immunological analysis and phenotypes, overview
-
-
-
additional information
?
-
-
high titers, and sustained intrathecal synthesis, of antibodies directed against neuronal glutamic acid decarboxylase, GAD, in paraneoplastic as well as non-paraneoplastic limbic encephalitis, phenotype, overview
-
-
-
additional information
?
-
-
isozyme GAD 65 in the stiff person syndrome causes GAD65-specific T cells accumulation in the central nervous system driving the intrathecal GAD65 IgG production, T cells from the cerebrospinal fluid, mechanism, overview. GAD65-specific T cells and clonally expanded GAD65-specific B cells coexist intrathecally, where they may collaborate in the synthesis of GAD65 IgG
-
-
-
additional information
?
-
-
latent autoimmune diabetes in adults, LADA, is a form of type 1 diabetes which is associated with autoimmuno response to the glutamate decarboxylase
-
-
-
additional information
?
-
-
leucoencephalopathy, transverse myelopathy, and peripheral neuropathy in children with cancer are associated with anti-GAD autoantibodies, overview
-
-
-
additional information
?
-
-
the smaller isoform of glutamate decarboxylase, GAD65, is a major autoantigen in type 1 diabetes, antigen presentation of detergent-free glutamate decarboxylase (GAD65) is affected by human serum albumin as carrier protein, immunoresponse analysis, overview
-
-
-
additional information
?
-
-
enzyme/transporter pair GAD2/T2 is primarily responsible for surviving severe acid challenge, enzyme GAD1 plays a major role in growth at mildly acidic pH-values
-
-
-
additional information
?
-
-
enzyme/transporter pair GAD2/T2 is primarily responsible for surviving severe acid challenge, enzyme GAD1 plays a major role in growth at mildly acidic pH-values
-
-
-
additional information
?
-
-
susceptibility of GABAergic neurons or GAD transcript regulation within the context of ischemic injury to neocerebral cortex, overview
-
-
-
additional information
?
-
-
isoform GAD65 plays a major role in gamma-aminobutanoate transmission in normal physiological condition. Isoform GAD67 can serve this role under some pathological conditions
-
-
-
additional information
?
-
-
cortical GABAergic neurons, surviving pathological insult such as ischemia or brain trauma, exposed to glutamate in vitro, display an NMDA receptor-mediated alteration in the levels of the GABA synthesizing enzyme glutamic acid decarboxylase, isozymes GAD65 and 67, mechanism of glutamate excitotoxicity, overview
-
-
-
additional information
?
-
-
GAD65 plays an essential role in neurotransmission, overview
-
-
-
additional information
?
-
-
cortical GABAergic neurons, surviving pathological insult such as ischemia or brain trauma, exposed to glutamate in vitro, display an NMDA receptor-mediated alteration in the levels of the GABA synthesizing enzyme glutamic acid decarboxylase, isozymes GAD65 and 67, mechanism of glutamate excitotoxicity, overview
-
-
-
additional information
?
-
-
the recombinant engineered enzyme shows a broad substrate specificity
-
-
-
additional information
?
-
-
calpains inhibit the GAD cleavage in vivo, overview
-
-
-
additional information
?
-
-
chronic systemic administration of an agonist of dopamine D1/D5-preferring receptors increases GAD mRNA levels in striatonigral neurons in intact and dopamine-depleted rats. striatal GAD67 mRNA levels were negatively correlated with nigral alpha1 mRNA levels in the dopamine-depleted but not dopamine-intact side. down-regulation of nigral GABAA receptors is linked to the increase in striatal GAD67 mRNA levels in the dopamine-depleted striatum. Different signaling pathways are involved in the modulation by dopamine D1/D5 receptors of GAD65 and GAD67 mRNA levels in striatonigral neurons, overview
-
-
-
additional information
?
-
-
GAD65 plays an essential role in neurotransmission, overview
-
-
-
additional information
?
-
-
regular performance of exercise results in extensive changes in the forebrain GABAergic system that may be implicated in the changes in stress sensitivity and emotionality observed in exercising subjects, overview
-
-
-
additional information
?
-
-
SDF1alpha/CXCR4/G protein/ERK signaling induces the expression of the GAD67 system via Egr1 activation, a mechanism that may promote the maturation of GABAergic neurons during development
-
-
-
additional information
?
-
-
the activity is closely associated with its developmental status and may represent a link between differentiation events and energy metabolism
-
-
-
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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-Glu
4-Aminobutanoate + CO2
-
rate-limiting enzyme involved in the synthesis of gamma-aminobutyric acid
-
-
?
L-Glu
?
-
the enzyme is under the control of the asexual developmental cycle
-
-
-
L-Glu
?
-
production of 4-aminobutanoate, which is the major inhibitory neurotransmitter in the mammalian brain
-
-
-
L-glutamate
4-aminobutanoate + CO2
-
GAD67 is a rate-limiting enzyme for GABA synthesis, GAD65 is important for the local control of GABA synthesis at the synaptic sites, whereas GAD67 is responsible for maintaining GABA baseline levels for both neurotransmitter and metabolite
-
-
?
L-glutamate
4-aminobutanoate + CO2
-
GAD is the rate-limiting enzyme for GABA biosynthesis
-
-
?
L-glutamate
4-aminobutanoate + CO2
-
GAD is the rate-limiting enzyme for GABA biosynthesis
-
-
?
L-glutamate
4-aminobutanoate + CO2
-
GAD is the key enzyme of GABA synthesis, alterations of GABAergic neurotransmission are assumed to play a crucial role in the pathophysiology of mood disorders, overview. Increased relative density of GAD-immunoreactive neuropil, suggests the diathesis of GABAergic system specific for depressed suicidal patients
-
-
?
L-glutamate
4-aminobutanoate + CO2
Q05329, Q99259
GAD is the rate-limiting enzyme in controlling GABA synthesis, GABA is synthesized by GAD67 is used for the other functions such as trophic factor for neuronal development or energy source. GAD67 is constitutively active and is responsible for the basal GABA production
-
-
?
L-glutamate
4-aminobutanoate + CO2
Q05329, Q99259
GAD is the rate-limiting enzyme in controlling GABA synthesis, GAD65 is transiently activated in response to the extra demand of GABA in neurotransmission
-
-
?
L-glutamate
4-aminobutanoate + CO2
-
GAD is the rate-limiting enzyme in neurotransmitter gamma-aminobutyric acid, GABA, biosynthesis
-
-
?
L-glutamate
4-aminobutanoate + CO2
-
human glutamic acid decarboxylase 65 is a key autoantigen in type 1 diabetes
-
-
?
L-glutamate
4-aminobutanoate + CO2
-
the isozymes are involved in autoimmune response and diseases, such as diabetes mellitus and Graves' disease, overview. Correlations between anti-GAD autoantibodies and diseases, overview
-
-
?
L-glutamate
4-aminobutanoate + CO2
-
-
-
-
?
L-glutamate
4-aminobutanoate + CO2
-
GAD is the rate-limiting enzyme in controlling GABA synthesis, GABA is synthesized by GAD67 is used for the other functions such as trophic factor for neuronal development or energy source. GAD67 is constitutively active and is responsible for the basal GABA production while GAD65 is transiently activated in response to the extra demand of GABA in neurotransmission
-
-
?
L-glutamate
4-aminobutanoate + CO2
-
GAD is the rate-limiting enzyme in neurotransmitter gamma-aminobutyric acid, GABA, biosynthesis
-
-
?
L-glutamate
4-aminobutanoate + CO2
-
GAD65-mediated GABA synthesis is critical for the consolidation of stimulus-specific fear memory. This function appears to involve a modulation of neural activity patterns in the amygdalo-hippocampal pathway as indicated by a reduction in theta frequency synchronization between the amygdala and hippocampus of Gad65-/- mice during the expression of generalized fear memory
-
-
?
L-glutamate
4-aminobutanoate + CO2
-
GAD67 is the rate-limiting enzyme of GABA biosynthesis
-
-
?
L-glutamate
4-aminobutanoate + CO2
-
nicotine, by activating nAChRs located on cortical or hippocampal GABAergic interneurons, can up-regulate GAD67 expression via an epigenetic mechanism
-
-
?
L-glutamate
4-aminobutanoate + CO2
-
GAD is the rate-limiting enzyme in controlling GABA synthesis, GABA is synthesized by GAD67 is used for the other functions such as trophic factor for neuronal development or energy source. GAD67 is constitutively active and is responsible for the basal GABA production while GAD65 is transiently activated in response to the extra demand of GABA in neurotransmission
-
-
?
L-glutamate
4-aminobutanoate + CO2
-
GAD is the rate-limiting enzyme in neurotransmitter gamma-aminobutyric acid, GABA, biosynthesis
-
-
?
L-glutamate
4-aminobutanoate + CO2
-
glutamate decarboxylase is the rate-limiting enzyme in the synthesis of gamma-aminobutyric acid, the most important inhibitory neurotransmitter in central nervous system
-
-
?
L-glutamate
4-aminobutanoate + CO2
-
the enzyme activity is higher in hippocampus of old rats compared to young rats
-
-
?
additional information
?
-
-
the reduction of GAD67 immunoreactive neurons in the hippocampal CA1 region may be closely related to highly susceptibility to memory loss in old aged dogs
-
-
-
additional information
?
-
-
GadB together with the antiporter gadC constitutes the gad acid resistance system, which confers the ability for bacterial survival for at least 2 h in a strongly acidic environment
-
-
-
additional information
?
-
-
of the two homolous forms of glutamic acid decarboxylase, GAD65 and GAD67, only GAD65 is a common target of autoimmunity
-
-
-
additional information
?
-
-
association of the two GAD isoforms in Irish individuals with Alzheimer's disease and relevant alcohol-related traits in the irish affected Sib pair study of alcohol dependence, overview. Significant association of GAD1 with initial sensitivity and age at onset of Alzheimer's disease
-
-
-
additional information
?
-
-
calpains inhibit the GAD cleavage in vivo, overview
-
-
-
additional information
?
-
-
enhanced anti-GAD antibodies are associated with several neurological diseases, possibly also the indiopathic Opsoclonus-myoclonus-ataxia syndrome, OMS. The anti-GAD antibodies might act via impairing GABAergic transmission in specific brainstem and cerebellar circuits, overview
-
-
-
additional information
?
-
-
GAD1 might be the susceptibility gene or another one being the susceptibility gene for autism, located on chromosome 2q31
-
-
-
additional information
?
-
Q05329
GAD65 plays an essential role in neurotransmission, and is a typical autoantigen in several human autoimmune diseases, such as insulin-dependent diabetes mellitus, IDDM and Stiffman-Person syndrome, SPS. Posttranslational regulation of the enzyme in brain, overview
-
-
-
additional information
?
-
Q99259
GAD65 plays an essential role in neurotransmission, and is a typical autoantigen in several human autoimmune diseases, such as insulin-dependent diabetes mellitus, IDDM and Stiffman-Person syndrome, SPS. Posttranslational regulation of the enzyme in brain, overview
-
-
-
additional information
?
-
-
high levels of autoantibodies to glutamic acid decarboxylase are associated with the stiff-person syndrome and type 1 diabetes mellitus and other pathologies, immunological analysis and phenotypes, overview
-
-
-
additional information
?
-
-
high titers, and sustained intrathecal synthesis, of antibodies directed against neuronal glutamic acid decarboxylase, GAD, in paraneoplastic as well as non-paraneoplastic limbic encephalitis, phenotype, overview
-
-
-
additional information
?
-
-
isozyme GAD 65 in the stiff person syndrome causes GAD65-specific T cells accumulation in the central nervous system driving the intrathecal GAD65 IgG production, T cells from the cerebrospinal fluid, mechanism, overview. GAD65-specific T cells and clonally expanded GAD65-specific B cells coexist intrathecally, where they may collaborate in the synthesis of GAD65 IgG
-
-
-
additional information
?
-
-
latent autoimmune diabetes in adults, LADA, is a form of type 1 diabetes which is associated with autoimmuno response to the glutamate decarboxylase
-
-
-
additional information
?
-
-
leucoencephalopathy, transverse myelopathy, and peripheral neuropathy in children with cancer are associated with anti-GAD autoantibodies, overview
-
-
-
additional information
?
-
-
the smaller isoform of glutamate decarboxylase, GAD65, is a major autoantigen in type 1 diabetes, antigen presentation of detergent-free glutamate decarboxylase (GAD65) is affected by human serum albumin as carrier protein, immunoresponse analysis, overview
-
-
-
additional information
?
-
-
enzyme/transporter pair GAD2/T2 is primarily responsible for surviving severe acid challenge, enzyme GAD1 plays a major role in growth at mildly acidic pH-values
-
-
-
additional information
?
-
-
enzyme/transporter pair GAD2/T2 is primarily responsible for surviving severe acid challenge, enzyme GAD1 plays a major role in growth at mildly acidic pH-values
-
-
-
additional information
?
-
-
susceptibility of GABAergic neurons or GAD transcript regulation within the context of ischemic injury to neocerebral cortex, overview
-
-
-
additional information
?
-
-
isoform GAD65 plays a major role in gamma-aminobutanoate transmission in normal physiological condition. Isoform GAD67 can serve this role under some pathological conditions
-
-
-
additional information
?
-
-
cortical GABAergic neurons, surviving pathological insult such as ischemia or brain trauma, exposed to glutamate in vitro, display an NMDA receptor-mediated alteration in the levels of the GABA synthesizing enzyme glutamic acid decarboxylase, isozymes GAD65 and 67, mechanism of glutamate excitotoxicity, overview
-
-
-
additional information
?
-
-
GAD65 plays an essential role in neurotransmission, overview
-
-
-
additional information
?
-
-
cortical GABAergic neurons, surviving pathological insult such as ischemia or brain trauma, exposed to glutamate in vitro, display an NMDA receptor-mediated alteration in the levels of the GABA synthesizing enzyme glutamic acid decarboxylase, isozymes GAD65 and 67, mechanism of glutamate excitotoxicity, overview
-
-
-
additional information
?
-
-
calpains inhibit the GAD cleavage in vivo, overview
-
-
-
additional information
?
-
-
chronic systemic administration of an agonist of dopamine D1/D5-preferring receptors increases GAD mRNA levels in striatonigral neurons in intact and dopamine-depleted rats. striatal GAD67 mRNA levels were negatively correlated with nigral alpha1 mRNA levels in the dopamine-depleted but not dopamine-intact side. down-regulation of nigral GABAA receptors is linked to the increase in striatal GAD67 mRNA levels in the dopamine-depleted striatum. Different signaling pathways are involved in the modulation by dopamine D1/D5 receptors of GAD65 and GAD67 mRNA levels in striatonigral neurons, overview
-
-
-
additional information
?
-
-
GAD65 plays an essential role in neurotransmission, overview
-
-
-
additional information
?
-
-
regular performance of exercise results in extensive changes in the forebrain GABAergic system that may be implicated in the changes in stress sensitivity and emotionality observed in exercising subjects, overview
-
-
-
additional information
?
-
-
SDF1alpha/CXCR4/G protein/ERK signaling induces the expression of the GAD67 system via Egr1 activation, a mechanism that may promote the maturation of GABAergic neurons during development
-
-
-
additional information
?
-
-
the activity is closely associated with its developmental status and may represent a link between differentiation events and energy metabolism
-
-
-
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Calmodulin
-
stimulation be Ca2+ plus calmodulin, no stimulation by Ca2+ or calmodulin alone
Calmodulin
-
Ca2+/calmodulin-dependent enzyme with calmodulin binding activity
Calmodulin
GAD can be regulated in vivo by Ca2+/calmodulin atpH 5.8. The addition of bovine calmodulin and Ca2+ to the reaction mix causes an activation of GAD activity of 32%
pyridoxal 5'-phosphate
-
one molecule of pyridoxal 5'-phosphate is covalently bound to a lysyl residue
pyridoxal 5'-phosphate
-
contains 2 mol of pyridoxal 5'-phosphate per mol of enzyme; Km: 0.02 mM
pyridoxal 5'-phosphate
-
bound cofactor. The enzyme is present in large amounts as apoenzyme, that can by activated when additional 4-aminobutanoate synthesis is required
pyridoxal 5'-phosphate
-
slower binding of pyridoxal 5'-phosphate to GAD67 than to GAD65, and less ease to dissociate pyridoxal 5'-phosphate from holoGAD67 than holoGAD54. TGAD67 is more highly saturated by the cofactor than GAD65. The two binding sites of GAD65 exhibit similar affinities for pyridoxal 5'-phosphate. One binding site of GAD67 exhibits a significantly higher affinity for pyridoxal 5'-phosphate than the other binding site
pyridoxal 5'-phosphate
-
the inactive mutant enzyme k276A contains very little pyridoxal 5'-phosphate, the inactive mutant enzyme K276H contains no pyridoxal 5'-phosphate
pyridoxal 5'-phosphate
-
activity of GST-GAD54, GAD65 and 6*His-GAD65 is nearly zero without exogenous pyridoxal 5'-phosphate. Activity of GST-GAD67 is 20% without exogenous pyridoxal 5'-phosphate. Activity of GAD67 is 32% without exogenous pyridoxal 5'-phosphate. Activity of 6*His-GAD67 is 30% without exogenous pyridoxal 5'-phosphate
pyridoxal 5'-phosphate
-
although GAD65 and GAD67 interact differently with pyridoxal 5'-phosphate, their cofactor-binding sites contain the same set of nine putative cofactor-binding residues and has the same basic structural fold. Thus the cofactor-binding differences cannot by attributed to fundamental structural differences between the GADs but must result from subtle modifications of the basic cofactor-binding fold
pyridoxal 5'-phosphate
-
Km-value 74 nM, wild-type, 490 nM, mutant with N-terminal deletion of 70 amino acids
pyridoxal 5'-phosphate
-
Km-value 70 nM for isoform GAD67, 70 nM for isoform GAD67 in presence of apocalmodulin, 490 nM isoform GAD67, lacking aminoterminal 70 amino acids, 320 nM for isoform GAD67, lacking aminoterminal 70 amino acids, in presence of apocalmodulin
pyridoxal 5'-phosphate
-
slight conformational change upon binding to apo-enzyme
pyridoxal 5'-phosphate
binding of pyridoxal 5'-phosphate as well as to the active site residues Thr215 and Asp246 that promote decarboxylation
pyridoxal 5'-phosphate
residue K279 is essential for cofactor binding
pyridoxal 5'-phosphate
-
the pyridine ring of pyridoxal 5'-phosphate is sandwiched between residues Ala248 and Gln166. Residues Lys279 and His278 are required for the binding of cofactor pyridoxal 5'-phosphate to form a Schiff base as in many other pyridoxal 5'-phosphate-dependent enzymes
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
Cl-
Mn2+
-
the optimal concentration (7.5 mM) of Mn2+ can also improve the activity of recombinant enzyme (164%), but the co-effect of Ca2+ and Mn2+ exhibits antagonism effect when added simultaneously
additional information
Ca2+
-
stimulation by Ca2+ plus calmodulin, no stimulation by Ca2+ or calmodulin alone
Ca2+
-
at a separate concentration of Ca2+ and calmodulin of 0.2 mM and 150 nM, the rice bran GAD is significantly enhanced 3fold
Ca2+
the addition of Ca2+ to the reaction mix causes an activation of GAD activity of 32%
Cl-
binding of chloride ions to the N-terminus could stabilizes the triple-helix bundle
additional information
-
Mn2+ shows no effect on glutamate decarboxylase activity
additional information
no effect on activity by NaCl, MgCl2, and MnCl2
additional information
-
removing extracellular calcium prevents the NMDAR-mediated decrease in GAD protein levels, whereas inhibiting calcium entry through voltage-gated calcium channels has no effect
additional information
MgCl2 and NaCl have no effect on enzyme activity
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INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1-Methylimidazole
-
about 85% residual activity at 5 mM, about 77% residual activity at 10 mM, about 65% residual activity at 20 mM
2-chloro-N-[5-([2-oxo-2-[(4-sulfamoylphenyl)amino]ethyl]sulfanyl)-1,3,4-thiadiazol-2-yl]acetamide
4'-deoxypyridoxine-5'-phosphate
-
about 60% inhibition of GAD65 at 3.5 mM, GAD67 is hardly affected
4'-O-methylpyridoxine-5'-phosphate
-
decreases activity of GAD65 in unphysiologically high concentrations, about 60% inhibition at 3.5 mM. GAD67 activity is hardly affected
4-methylimidazole
-
about 75% residual activity at 5 mM, about 70% residual activity at 10 mM, about 58% residual activity at 20 mM
5-[(E)-[[1-(2-chlorobenzyl)-1H-indol-3-yl]methylidene]amino]-1,3-dihydro-2H-benzimidazol-2-one
5-[[5-hydroxy-3-methyl-1-(4-methylphenyl)-1H-pyrazol-4-yl]methylidene]-1,3-diphenyl-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
ATP
-
in presence of leupeptin in freshly prepared homogenates. Inhibition of enzyme from homogenates stored without Triton X-100 for 24 h at 4°C
Chloroacetamide
-
no inhibition at pH 4.6, marked inhibition at pH 6.0 or higher
cyclosporin A
-
up to 0.3 mM, partial inhibition of activity in homogenate, but not in the supernatant obtained after centrifuging the homogenate
ginsenosides
-
23% inhibition at 0.01 mg/ml, ethanol extract of Panax quinquefolius, different glycoside derivatives, overview
-
isoniazide
isoniazide-induced seizures are mediated primarily through competition with the cofactor pyridoxal 5'-phosphate resulting in the inhibition of GAD activity
(4Z,7E)-N,N'-dihydroxy-2,2-dimethyl-5,6-dihydro-2H-benzimidazole-4,7-diimine
-
(4Z,7E)-N,N'-dihydroxy-2,2-dimethyl-5,6-dihydro-2H-benzimidazole-4,7-diimine
-
(4Z,7E)-N,N'-dihydroxy-2,2-dimethyl-5,6-dihydro-2H-benzimidazole-4,7-diimine
;
(4Z,7E)-N,N'-dihydroxy-2,2-dimethyl-5,6-dihydro-2H-benzimidazole-4,7-diimine
-
1,4-dioxo-1,2,3,4-tetrahydronaphthalen-2-yl 2,3,4-tri-O-acetylpentopyranoside
-
1,4-dioxo-1,2,3,4-tetrahydronaphthalen-2-yl 2,3,4-tri-O-acetylpentopyranoside
-
1,4-dioxo-1,2,3,4-tetrahydronaphthalen-2-yl 2,3,4-tri-O-acetylpentopyranoside
;
1,4-dioxo-1,2,3,4-tetrahydronaphthalen-2-yl 2,3,4-tri-O-acetylpentopyranoside
-
2-(benzylsulfanyl)-3-(morpholin-4-yl)-2,3-dihydronaphthalene-1,4-dione
-
2-(benzylsulfanyl)-3-(morpholin-4-yl)-2,3-dihydronaphthalene-1,4-dione
-
2-(benzylsulfanyl)-3-(morpholin-4-yl)-2,3-dihydronaphthalene-1,4-dione
;
2-(benzylsulfanyl)-3-(morpholin-4-yl)-2,3-dihydronaphthalene-1,4-dione
-
2-chloro-N-[5-([2-oxo-2-[(4-sulfamoylphenyl)amino]ethyl]sulfanyl)-1,3,4-thiadiazol-2-yl]acetamide
-
2-chloro-N-[5-([2-oxo-2-[(4-sulfamoylphenyl)amino]ethyl]sulfanyl)-1,3,4-thiadiazol-2-yl]acetamide
-
2-chloro-N-[5-([2-oxo-2-[(4-sulfamoylphenyl)amino]ethyl]sulfanyl)-1,3,4-thiadiazol-2-yl]acetamide
;
2-chloro-N-[5-([2-oxo-2-[(4-sulfamoylphenyl)amino]ethyl]sulfanyl)-1,3,4-thiadiazol-2-yl]acetamide
-
2-hydroxy-2-(2-hydroxy-6-oxocyclohex-2-en-1-yl)-1H-indene-1,3(2H)-dione
-
2-hydroxy-2-(2-hydroxy-6-oxocyclohex-2-en-1-yl)-1H-indene-1,3(2H)-dione
-
2-hydroxy-2-(2-hydroxy-6-oxocyclohex-2-en-1-yl)-1H-indene-1,3(2H)-dione
;
2-hydroxy-2-(2-hydroxy-6-oxocyclohex-2-en-1-yl)-1H-indene-1,3(2H)-dione
-
2-thioxo-3-[(E)-(3,3,5-trimethylcyclohexylidene)amino]-1,3-thiazolidin-4-one
-
2-thioxo-3-[(E)-(3,3,5-trimethylcyclohexylidene)amino]-1,3-thiazolidin-4-one
-
2-thioxo-3-[(E)-(3,3,5-trimethylcyclohexylidene)amino]-1,3-thiazolidin-4-one
;
2-thioxo-3-[(E)-(3,3,5-trimethylcyclohexylidene)amino]-1,3-thiazolidin-4-one
-
3,3'-(4H-1,2,4-triazole-3,5-diyl)bis(4-nitro-1,2,5-oxadiazole)
-
3,3'-(4H-1,2,4-triazole-3,5-diyl)bis(4-nitro-1,2,5-oxadiazole)
-
3,3'-(4H-1,2,4-triazole-3,5-diyl)bis(4-nitro-1,2,5-oxadiazole)
-
3-[(2E)-2-[1-(3,4-dimethoxyphenyl)ethylidene]hydrazinyl]benzoic acid
-
3-[(2E)-2-[1-(3,4-dimethoxyphenyl)ethylidene]hydrazinyl]benzoic acid
-
3-[(2E)-2-[1-(3,4-dimethoxyphenyl)ethylidene]hydrazinyl]benzoic acid
;
3-[(2E)-2-[1-(3,4-dimethoxyphenyl)ethylidene]hydrazinyl]benzoic acid
-
3-[(E)-(2,6-difluorobenzylidene)amino]-2-thioxo-1,3-thiazolidin-4-one
-
3-[(E)-(2,6-difluorobenzylidene)amino]-2-thioxo-1,3-thiazolidin-4-one
-
3-[(E)-(2,6-difluorobenzylidene)amino]-2-thioxo-1,3-thiazolidin-4-one
;
3-[(E)-(2,6-difluorobenzylidene)amino]-2-thioxo-1,3-thiazolidin-4-one
-
3-[(E)-(4-methoxybenzylidene)amino]-2-thioxo-1,3-thiazolidin-4-one
-
3-[(E)-(4-methoxybenzylidene)amino]-2-thioxo-1,3-thiazolidin-4-one
-
3-[(E)-(4-methoxybenzylidene)amino]-2-thioxo-1,3-thiazolidin-4-one
;
3-[(E)-(4-methoxybenzylidene)amino]-2-thioxo-1,3-thiazolidin-4-one
-
4,4'-(phenylmethanediyl)bis[2-(4-chlorophenyl)-5-methyl-2,4-dihydro-3H-pyrazol-3-one]
-
4,4'-(phenylmethanediyl)bis[2-(4-chlorophenyl)-5-methyl-2,4-dihydro-3H-pyrazol-3-one]
-
4,4'-(phenylmethanediyl)bis[2-(4-chlorophenyl)-5-methyl-2,4-dihydro-3H-pyrazol-3-one]
;
4,4'-(phenylmethanediyl)bis[2-(4-chlorophenyl)-5-methyl-2,4-dihydro-3H-pyrazol-3-one]
-
4,4'-[(4-hydroxyphenyl)methanediyl]bis(2-heptyl-5-methyl-2,4-dihydro-3H-pyrazol-3-one)
-
4,4'-[(4-hydroxyphenyl)methanediyl]bis(2-heptyl-5-methyl-2,4-dihydro-3H-pyrazol-3-one)
-
4,4'-[(4-hydroxyphenyl)methanediyl]bis(2-heptyl-5-methyl-2,4-dihydro-3H-pyrazol-3-one)
;
4,4'-[(4-hydroxyphenyl)methanediyl]bis(2-heptyl-5-methyl-2,4-dihydro-3H-pyrazol-3-one)
-
4-nitro-7-[[(1-phenyl-1H-tetrazol-5-yl)sulfanyl]methyl]-2,1,3-benzothiadiazole
-
4-nitro-7-[[(1-phenyl-1H-tetrazol-5-yl)sulfanyl]methyl]-2,1,3-benzothiadiazole
-
4-nitro-7-[[(1-phenyl-1H-tetrazol-5-yl)sulfanyl]methyl]-2,1,3-benzothiadiazole
;
4-nitro-7-[[(1-phenyl-1H-tetrazol-5-yl)sulfanyl]methyl]-2,1,3-benzothiadiazole
-
4-[(1,4-dioxo-1,2,3,4-tetrahydronaphthalen-2-yl)sulfanyl]butanoic acid
-
4-[(1,4-dioxo-1,2,3,4-tetrahydronaphthalen-2-yl)sulfanyl]butanoic acid
-
4-[(1,4-dioxo-1,2,3,4-tetrahydronaphthalen-2-yl)sulfanyl]butanoic acid
;
4-[(1,4-dioxo-1,2,3,4-tetrahydronaphthalen-2-yl)sulfanyl]butanoic acid
-
5,5'-dithiobis(2-nitrobenzoate)
-
0.1 mM, 50.3% inhibition at pH 4.6, irreversible
5-[(E)-benzylideneamino]-6-[(2-hydroxyethyl)amino]pyrimidine-2,4(1H,3H)-dione
-
5-[(E)-benzylideneamino]-6-[(2-hydroxyethyl)amino]pyrimidine-2,4(1H,3H)-dione
-
5-[(E)-benzylideneamino]-6-[(2-hydroxyethyl)amino]pyrimidine-2,4(1H,3H)-dione
;
5-[(E)-benzylideneamino]-6-[(2-hydroxyethyl)amino]pyrimidine-2,4(1H,3H)-dione
-
5-[(E)-[[1-(2-chlorobenzyl)-1H-indol-3-yl]methylidene]amino]-1,3-dihydro-2H-benzimidazol-2-one
-
5-[(E)-[[1-(2-chlorobenzyl)-1H-indol-3-yl]methylidene]amino]-1,3-dihydro-2H-benzimidazol-2-one
-
5-[(E)-[[1-(2-chlorobenzyl)-1H-indol-3-yl]methylidene]amino]-1,3-dihydro-2H-benzimidazol-2-one
;
5-[(E)-[[1-(2-chlorobenzyl)-1H-indol-3-yl]methylidene]amino]-1,3-dihydro-2H-benzimidazol-2-one
-
5-[[5-hydroxy-3-methyl-1-(4-methylphenyl)-1H-pyrazol-4-yl]methylidene]-1,3-diphenyl-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
-
5-[[5-hydroxy-3-methyl-1-(4-methylphenyl)-1H-pyrazol-4-yl]methylidene]-1,3-diphenyl-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
-
5-[[5-hydroxy-3-methyl-1-(4-methylphenyl)-1H-pyrazol-4-yl]methylidene]-1,3-diphenyl-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
;
5-[[5-hydroxy-3-methyl-1-(4-methylphenyl)-1H-pyrazol-4-yl]methylidene]-1,3-diphenyl-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
-
6,11-dioxo-5a,6,11,11a-tetrahydronaphtho[2',3':4,5][1,3]thiazolo[3,2-a]pyridin-12-ium
-
6,11-dioxo-5a,6,11,11a-tetrahydronaphtho[2',3':4,5][1,3]thiazolo[3,2-a]pyridin-12-ium
-
6,11-dioxo-5a,6,11,11a-tetrahydronaphtho[2',3':4,5][1,3]thiazolo[3,2-a]pyridin-12-ium
;
6,11-dioxo-5a,6,11,11a-tetrahydronaphtho[2',3':4,5][1,3]thiazolo[3,2-a]pyridin-12-ium
-
methyl 2-[[(2-methylimidazo[1,2-a]pyridin-3-yl)carbonyl]amino]benzoate
-
methyl 2-[[(2-methylimidazo[1,2-a]pyridin-3-yl)carbonyl]amino]benzoate
-
methyl 2-[[(2-methylimidazo[1,2-a]pyridin-3-yl)carbonyl]amino]benzoate
;
methyl 2-[[(2-methylimidazo[1,2-a]pyridin-3-yl)carbonyl]amino]benzoate
-
N-[4,7-dioxo-6-(phenylamino)-4,7-dihydro-2,1,3-benzoxadiazol-5-yl]acetamide
-
N-[4,7-dioxo-6-(phenylamino)-4,7-dihydro-2,1,3-benzoxadiazol-5-yl]acetamide
-
N-[4,7-dioxo-6-(phenylamino)-4,7-dihydro-2,1,3-benzoxadiazol-5-yl]acetamide
;
N-[4,7-dioxo-6-(phenylamino)-4,7-dihydro-2,1,3-benzoxadiazol-5-yl]acetamide
-
N-[4,7-dioxo-6-(piperidin-1-yl)-4,7-dihydro-2,1,3-benzoxadiazol-5-yl]acetamide
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N-[4,7-dioxo-6-(piperidin-1-yl)-4,7-dihydro-2,1,3-benzoxadiazol-5-yl]acetamide
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N-[4,7-dioxo-6-(piperidin-1-yl)-4,7-dihydro-2,1,3-benzoxadiazol-5-yl]acetamide
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N-[4,7-dioxo-6-(piperidin-1-yl)-4,7-dihydro-2,1,3-benzoxadiazol-5-yl]acetamide
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additional information
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the glutamate decarboxylase activity of p42 is not inhibited by high concentrations of Mn2+
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additional information
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ionomycin inhibits the expression of the full-length enzyme, but not of the truncated mutant, while mu-calpain and calpastatin inhibit the truncated enzyme, but not the full-length wild-type enzyme in the synaptosome, overview
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additional information
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enzyme inhibition by glutamic acid decarboxylase autoantibodies, overview
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additional information
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aasiaticoside does not inhibit GAD activity even at the highest dose of 0.03 mg/ml. Allylglycine does not inhibit GAD activity even at the highest dose of 0.1 mM; asiaticoside does not inhibit GAD activity even at the highest dose of 0.03 mg/ml, allylglycine exhibits no enzyme inhibition even at the highest dose of 0.1 mM; minor inhibition is seen with the ethanol extract of Panax quinquefolius (23%), betulinic acid (27%), and valerenic acid (20%); minor inhibition is seen with the ethanol extract of Panax quinquefolius (ginsenosides) (23%)
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additional information
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under acidic conditions, glutamate/4-aminobutanoate antiport is impaired in minimal media but not in rich ones
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additional information
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glutamate reduces the expression of isozymes GAD65 and GAD67, glutamate's suppressing effect on GAD protein isoforms is significantly attenuated by preincubation with the cysteine protease inhibitor N-acetyl-L-leucyl-L-leucyl-L-norleucinal via blockade of calpain and cathepsin protease activities, overview
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additional information
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downregulation of reelin and GAD67 expression by the increase of DNA-methyltransferase 1-mediated hypermethylation of promoters in GABAergic interneurons of the telencephalon
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additional information
inhibitor screening, overview; inhibitor screening, overview
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additional information
inhibitor screening, overview; inhibitor screening, overview
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additional information
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ionomycin inhibits the expression of the full-length enzyme, but not of the truncated mutant, while mu-calpain and calpastatin inhibit the truncated enzyme, but not the full-length wild-type enzyme in the synaptosome, overview
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additional information
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chronic mild stress leads to 60% reduced enzyme activity in old rats, which is reversible by neuronal nitric oxide synthase inhibitor 7-nitroindazole, overview
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additional information
poor inhibition by LiCl, CaCl2, and KCl. MgCl2 and NaCl have no effect on enzyme activity
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ADP
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2 mM, activation to about 170% of control without detergent. Activation to about 210% of control in presence of 1% Triton X-100
AMP
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2 mM, activation to about 125% of control without detergent. Activation to about 140% of control in presence of 1% Triton X-100
apocalmodulin
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isoform GAD65, up to 60% activation, truncated isoform DAD67, up to 141% activation, no significant activation of GST-GAD67. Activation is due to an increase in affinity for cofactor pyridoxal 5'-phosphate
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asiaticoside
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20% activation at 0.01 mg/ml; an increase in GAD65 activity by 22% is observed with asiaticoside; an increase in GAD65 activity by 4.5% is observed with asiaticoside
ATP
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2 mM, activation to about 150% of control in presence of 1% Triton, inhibition to 20% of control without detergent
bilobalide
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20% activation at 0.01 mg/ml; an increase in GAD65 activity by 17.8% is observed with bilobalide; an increase in GAD65 activity by approximately 18% is observed with bilobalide
CTP
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2 mM, activation to about 110% of control without detergent. Activation to about 200% of control in presence of 1% Triton X-100
GTP
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2 mM, activation to about 125% of control without detergent. Activation to about 190% of control in presence of 1% Triton X-100
UTP
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2 mM, activation to about 140% of control without detergent. Activation to about 190% of control in presence of 1% Triton X-100
Ca2+
48% activation, up to 200% activation in presence of both Ca2+ and calmodulin
Ca2+
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24fold activation of wild-type in presence of both Ca2+ and calmodulin. For mutant lacking 19 amino acids at N-terminus, 12.9fold activation. Mutant lacking 9 amino acids at C-terminus, complete loss of activation
Calmodulin
activates Gad1 in a unique way by relieving two C-terminal autoinhibition domains of adjacent active sites, forming a 393 kDa Gad-Ca2+/calmodulin complex with a 1:3 stoichiometry
Calmodulin
42% activation, up to 200% activation in presence of both Ca2+ and calmodulin
Calmodulin
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at a separate concentration of Ca2+ and calmodulin of 0.2 mM and 150 nM, the rice bran GAD is significantly enhanced 3fold. Addition of exogenous EGTA or TFP efficiently inhibited the stimulatory effect of Ca2+/CaM complex
Calmodulin
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24fold activation of wild-type in presence of both Ca2+ and calmodulin. For mutant lacking 19 amino acids at N-terminus, 12.9fold activation. Mutant lacking 9 amino acids at C-terminus, complete loss of activation
additional information
sodium glutamate is essential for tetramer formation and its activation
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additional information
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AD67 immunoreactivity in the hippocampal CA1 region is significantly increased 24 h after ischemia/reperfusion
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additional information
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nicotine decreases inhibitory DNA-methyltransferase 1 mRNA and protein and increases GAD67 expression in the mouse frontal cortex, it diminishes the level of cytosine-5-methylation in the GAD67 promoter and prevents the methionine-induced hypermethylation of the same promoter. Nicotine effects are prevented by pretreatment with mecamylamine, overview
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6-azauracil and Phe decrease specificity for L-Glu and increased specificity to L-Asp
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additional information
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stromal cell-derived factor alpha, SDF1alpha, rapidly induces the expression of the early growth response gene Egr1, a transcription factor involved in activity-dependent neuronal responses, in a concentration-dependent manner, which increases the expression of GAD67 at both the mRNA and protein levels, and increases the amount and neurite localization of gamma-aminobutyric acid, GABA, in neurons already expressing GABA. SDF1alpha-induced Egr1/GAD67 expression is mediated by the G protein-coupled CXCR4 receptor and activation of the ERK pathway, overview
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additional information
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increased GAD or vGAT mRNA levels after acute SKF-81297 occurr in striatonigral neurons. Subchronic SKF-81297 induces significant increases in striatal GAD67, GAD65, preprodynorphin, and vGAT mRNA levels and decreases in nigral alpha1 mRNA levels. In the striatum contralateral to the 6-OHDA lesion, subchronic but not acute SKF-81297 induced a significant increase in GAD65 mRNA levels
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additional information
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a model to link neuronal excitation and activation of L-glutamate decarboxylase by Ca2+-dependent phosphatase
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1.04