Information on EC 4.1.1.15 - Glutamate decarboxylase

Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Specify your search results
Mark a special word or phrase in this record:
Select one or more organisms in this record:
Show additional data
Do not include text mining results
Include (text mining) results (more...)
Include results (AMENDA + additional results, but less precise; more...)


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

EC NUMBER
COMMENTARY
4.1.1.15
-
RECOMMENDED NAME
GeneOntology No.
Glutamate decarboxylase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
L-glutamate = 4-aminobutanoate + CO2
show the reaction diagram
-
-
-
-
L-glutamate = 4-aminobutanoate + CO2
show the reaction diagram
reaction proceeds via radical mechanism
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
decarboxylation
-
-
-
-
decarboxylation
-
-
oxidative deamination
-
-
PATHWAY
KEGG Link
MetaCyc Link
Alanine, aspartate and glutamate metabolism
-
beta-Alanine metabolism
-
Biosynthesis of secondary metabolites
-
Butanoate metabolism
-
GABA shunt
-
glutamate degradation IV
-
glutamate degradation IX (via 4-aminobutyrate)
-
glutamate dependent acid resistance
-
Metabolic pathways
-
Taurine and hypotaurine metabolism
-
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.
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
42 kDa biotin-coupled protein
-
exhibits both glutamine synthetase activity and glutamate decarboxylase activity
65 kDa glutamic acid decarboxylase
-
-
-
-
67 kDa glutamic acid decarboxylase
-
-
-
-
Aspartate 1-decarboxylase
-
-
-
-
Aspartic alpha-decarboxylase
-
-
-
-
Cysteic acid decarboxylase
-
-
-
-
Decarboxylase, glutamate
-
-
-
-
ERT D1
-
-
-
-
GAD
-
-
-
-
GAD
Dugesia japonica SSP
-
-
-
GAD
Q05329, Q99259
-
GAD
Lactobacillus brevis CGMCC
-
-
-
GAD
Lactobacillus brevis IFO12005
A9ZM78
-
-
GAD
Lactobacillus brevis Lb85
-
-
-
GAD
Lactobacillus paracasei NFRI 7415
B1B389
-
-
GAD
Lactobacillus plantarum ATCC 14917
-
-
-
GAD
B2ZX20
-
GAD
Mus musculus B6D2, Mus musculus BALB/c
-
-
-
GAD
Q9AR41
-
GAD
A0EJ89
-
GAD-65
-
-
-
-
GAD-67
-
-
-
-
GAD-alpha
-
-
-
-
GAD-beta
-
-
-
-
GAD-gamma
-
-
-
-
GAD1
Q7XJB3
-
GAD1
-
-
GAD1
-
-
GAD2
-
-
GAD3
-
-
GAD65
-
; isoform
GAD65
Q05329
-
GAD65
-
65 kDa isoform of glutamic acid decarboxylase
GAD65
-
65-kDa isoform of GAD
GAD65
-
65-kilodalton isoform of glutamate decarboxylase
GAD65
Rattus norvegicus LEW-1A
-
-
-
GAD65
-
-
GAD67
Q99259
-
GAD67
-
67 kDa form of the glutamic acid decarboxylase
GADCase
-
-
-
-
gamma-Glutamate decarboxylase
-
-
-
-
GDCase
-
-
-
-
glutamate decarboxylase
-
-
glutamate decarboxylase 1
-
-
glutamate decarboxylase 65
-
-
glutamate decarboxylase 67
-
-
Glutamic acid decarboxylase
-
-
-
-
Glutamic acid decarboxylase
-, Q4PRC2
-
Glutamic acid decarboxylase
-
-
Glutamic acid decarboxylase
Dugesia japonica SSP
-
-
-
Glutamic acid decarboxylase
-
-
Glutamic acid decarboxylase
Q7XJB3
-
Glutamic acid decarboxylase
Q05329, Q99259
-
Glutamic acid decarboxylase
-
-
Glutamic acid decarboxylase
B2ZX20
-
Glutamic acid decarboxylase
Mus musculus BALB/c
-
-
-
Glutamic acid decarboxylase
-
-
Glutamic acid decarboxylase
Rattus norvegicus LEW-1A
-
-
-
Glutamic acid decarboxylase
-
-
glutamic acid decarboxylase 65
-
; isoform
glutamic acid decarboxylase 65
-
65 kDa isoform of glutamic acid decarboxylase
glutamic acid decarboxylase 65
-
-
glutamic acid decarboxylase 67
-
-
glutamic acid decarboxylase 67
-
-
glutamic acid decarboxylase 67
-
-
glutamic acid decarboxylase 67
-
-
glutamic acid decarboxylase 67
-
67 kDa form of the glutamic acid decarboxylase
glutamic acid decarboxylase-65
-
-
glutamic acid decarboxylase-67
-
-
glutamic acid decarboxylase67
Q99259
-
Glutamic decarboxylase
-
-
-
-
L-Aspartate-alpha-decarboxylase
-
-
-
-
L-Glutamate alpha-decarboxylase
-
-
-
-
L-Glutamate decarboxylase
-
-
-
-
L-Glutamate decarboxylase
-
-
L-Glutamic acid decarboxylase
-
-
-
-
L-Glutamic acid decarboxylase
-
-
L-Glutamic acid decarboxylase
Q05329, Q99259
-
L-Glutamic acid decarboxylase
-
-
L-Glutamic decarboxylase
-
-
-
-
MGAD
-
-
-
-
p42
-
exhibits both glutamine synthetase activity and glutamate decarboxylase activity
MGAD
-
membrane-associated form of L-glutamate decarboxylase
additional information
-
GAD belongs to a subset of pyridoxal 5'-phosphate-dependent enzymes classified as group 2
CAS REGISTRY NUMBER
COMMENTARY
9024-58-2
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
strain L. Heynh. Ecotype Columbia, 2 isoenzymes: GAD1 and GAD2
-
-
Manually annotated by BRENDA team
GAD2; gene GAD2
UniProt
Manually annotated by BRENDA team
isoform GAD65, comparison with human isoform GAD65
-
-
Manually annotated by BRENDA team
strain SSP
-
-
Manually annotated by BRENDA team
Dugesia japonica SSP
strain SSP
-
-
Manually annotated by BRENDA team
isozyme GADalpha
-
-
Manually annotated by BRENDA team
alcohol dependent and non-alcohol dependent individuals of Irish origin, male and female
-
-
Manually annotated by BRENDA team
coexpression with murine IL-4 in tobacco
-
-
Manually annotated by BRENDA team
GAD65
UniProt
Manually annotated by BRENDA team
GAD67
UniProt
Manually annotated by BRENDA team
gene GAD1 encodes the isozyme GAD67
-
-
Manually annotated by BRENDA team
gene GAD65
-
-
Manually annotated by BRENDA team
isoform GAD65
-
-
Manually annotated by BRENDA team
isoform GAD65 and GAD67
-
-
Manually annotated by BRENDA team
isoform GAD65, comparison with goldfish isoform GAD65
-
-
Manually annotated by BRENDA team
isoform GAD67, patients diagnosed with major unipolar depression
-
-
Manually annotated by BRENDA team
isozymes GAD65 and GAD67
-
-
Manually annotated by BRENDA team
patients with diabetes and thyroid autoimmune diseases
-
-
Manually annotated by BRENDA team
recombinant isoform GAD67
-
-
Manually annotated by BRENDA team
recombinant isoforms GAD65 and GAD67
-
-
Manually annotated by BRENDA team
smaller isoform of glutamate decarboxylase, GAD65
-
-
Manually annotated by BRENDA team
two isozymes Gad65 and GAd67, male and female Graves' disease patients
-
-
Manually annotated by BRENDA team
type 1 diabetes mellitus patients
-
-
Manually annotated by BRENDA team
IFO 12005
-
-
Manually annotated by BRENDA team
strain IFO12005, gene gadB
A9ZM78
UniProt
Manually annotated by BRENDA team
Lactobacillus brevis CGMCC
-
-
-
Manually annotated by BRENDA team
Lactobacillus brevis IFO12005
strain IFO12005, gene gadB
A9ZM78
UniProt
Manually annotated by BRENDA team
Lactobacillus brevis Lb85
-
-
-
Manually annotated by BRENDA team
gene gadB; strain NFRI 7415, gene gadB
UniProt
Manually annotated by BRENDA team
Lactobacillus paracasei NFRI 7415
gene gadB; strain NFRI 7415, gene gadB
UniProt
Manually annotated by BRENDA team
Lactobacillus plantarum ATCC 14917
-
-
-
Manually annotated by BRENDA team
serovars 1/2a and 4b
-
-
Manually annotated by BRENDA team
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
-
-
Manually annotated by BRENDA team
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
-
-
Manually annotated by BRENDA team
male monkeys
-
-
Manually annotated by BRENDA team
isoform GAD65
-
-
Manually annotated by BRENDA team
Balb/c mice
-
-
Manually annotated by BRENDA team
C57BL/6 mice
-
-
Manually annotated by BRENDA team
gene GAD67
-
-
Manually annotated by BRENDA team
male C57BI/6 mice, genes GAD65 and GAD67 encoding the 65-kDa and the 67-kDa isozymes of glutamic acid decarboxylase
-
-
Manually annotated by BRENDA team
male FVB/NJ mice
SwissProt
Manually annotated by BRENDA team
strain B6D2
-
-
Manually annotated by BRENDA team
Mus musculus B6D2
strain B6D2
-
-
Manually annotated by BRENDA team
Mus musculus BALB/c
Balb/c mice
-
-
Manually annotated by BRENDA team
spleen from Dasypus novemcinctus infected with Mycobacterium leprae
-
-
Manually annotated by BRENDA team
no activity in Lactococcus lactis subsp. cremoris
-
-
-
Manually annotated by BRENDA team
-
Swissprot
Manually annotated by BRENDA team
cultivar Shangshi Jing 315
-
-
Manually annotated by BRENDA team
expression in Bifidobacterium longum
-
-
Manually annotated by BRENDA team
isoform GAD2
UniProt
Manually annotated by BRENDA team
gene PH0937
-
-
Manually annotated by BRENDA team
isoforms GAD65 and GAD67
-
-
Manually annotated by BRENDA team
isoforms GAD65 and GAD67, expression in Sf9/baculovirus system
-
-
Manually annotated by BRENDA team
isozymes GAD67 and GAD65, encoded by different genes
-
-
Manually annotated by BRENDA team
male sprague-dawley rats
-
-
Manually annotated by BRENDA team
male Wistar rats
-
-
Manually annotated by BRENDA team
strain LEW-1A and BB/OK
-
-
Manually annotated by BRENDA team
Rattus norvegicus LEW-1A
strain LEW-1A and BB/OK
-
-
Manually annotated by BRENDA team
serotypes Typhimurium and Enteritidis
-
-
Manually annotated by BRENDA team
ssp. thermophilus Y2, gene gadB
UniProt
Manually annotated by BRENDA team
inbred line DH4866
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
malfunction
-
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
-
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
-
GAD1 plays an important role in responses to abiotic factors and hormone treatments
physiological function
A0EJ89, -
GAD plays a role in hypocotyl and stem development in pine
physiological function
-
possession of the gadD1 gene correlates with a higher degree of tolerance to nisin
-
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
L-alpha-Methylglutamate
?
show the reaction diagram
-
-
-
-
-
L-alpha-methylglutamate + O2
laevulinic acid + NH3
show the reaction diagram
-
-
-
-
?
L-Asp
?
show the reaction diagram
-
3-5% of the activity with L-Glu
-
-
-
L-Asp
?
show the reaction diagram
-
2% of the activity with L-Glu
-
-
-
L-Asp
?
show the reaction diagram
-
Phe or 6-azauracil decrease specificity for L-Glu and increase specificity to L-Asp
-
-
-
L-Cysteic acid
?
show the reaction diagram
-
-
-
-
-
L-Cysteine sulfinic acid
?
show the reaction diagram
-
-
-
-
-
L-Cysteine sulfinic acid
?
show the reaction diagram
-
8% of the activity with L-Glu
-
-
-
L-Glu
4-Aminobutanoate + CO2
show the reaction diagram
-
-
-
-
-
L-Glu
4-Aminobutanoate + CO2
show the reaction diagram
-
-
-
-
-
L-Glu
4-Aminobutanoate + CO2
show the reaction diagram
-
-
-
-
-
L-Glu
4-Aminobutanoate + CO2
show the reaction diagram
-
-
-
-
?
L-Glu
4-Aminobutanoate + CO2
show the reaction diagram
-
-
-
-
-
L-Glu
4-Aminobutanoate + CO2
show the reaction diagram
-
-
-
-
?
L-Glu
4-Aminobutanoate + CO2
show the reaction diagram
-
-
-
-
-
L-Glu
4-Aminobutanoate + CO2
show the reaction diagram
-
-
-
-
?
L-Glu
4-Aminobutanoate + CO2
show the reaction diagram
-
-
-
-
-
L-Glu
4-Aminobutanoate + CO2
show the reaction diagram
-
-
-
-
-
L-Glu
4-Aminobutanoate + CO2
show the reaction diagram
-
-
-
-
-
L-Glu
4-Aminobutanoate + CO2
show the reaction diagram
-
-
-
-
-
L-Glu
4-Aminobutanoate + CO2
show the reaction diagram
-
-
-
-
-
L-Glu
4-Aminobutanoate + CO2
show the reaction diagram
-
-
-
-
-
L-Glu
4-Aminobutanoate + CO2
show the reaction diagram
-
-
-
-
-
L-Glu
4-Aminobutanoate + CO2
show the reaction diagram
-
-
-
-
-
L-Glu
4-Aminobutanoate + CO2
show the reaction diagram
-
-
-
-
-
L-Glu
4-Aminobutanoate + CO2
show the reaction diagram
-
-
-
-
-
L-Glu
4-Aminobutanoate + CO2
show the reaction diagram
-
-
-
-
L-Glu
4-Aminobutanoate + CO2
show the reaction diagram
-
-
-
-
-
L-Glu
4-Aminobutanoate + CO2
show the reaction diagram
-
-
-
-
?
L-Glu
4-Aminobutanoate + CO2
show the reaction diagram
-
-
-
-
-
L-Glu
4-Aminobutanoate + CO2
show the reaction diagram
-
-
-
-
-
L-Glu
4-Aminobutanoate + CO2
show the reaction diagram
-
-
-
-
?
L-Glu
4-Aminobutanoate + CO2
show the reaction diagram
-
-
-
-
?
L-Glu
4-Aminobutanoate + CO2
show the reaction diagram
-
6-azauracil or Phe decrease specificity for L-Glu and increased specificity to L-Asp
-
-
-
L-Glu
4-Aminobutanoate + CO2
show the reaction diagram
-
rate-limiting enzyme involved in the synthesis of gamma-aminobutyric acid
-
-
?
L-Glu
?
show the reaction diagram
-
production of 4-aminobutanoate, which is the major inhibitory neurotransmitter in the mammalian brain
-
-
-
L-Glu
?
show the reaction diagram
-
isoenzyme GAD2 may play a unique role in nitrogen metabolism
-
-
-
L-Glu
?
show the reaction diagram
-
the enzyme is under the control of the asexual developmental cycle
-
-
-
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
-
-
-
-
?
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
-
-
-
-
?
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
-
-
-
-
?
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
P69910
-
-
-
?
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
-
-
-
-
?
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
-
-
-
-
?
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
-
-
-
-
?
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
-
-
-
-
?
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
-
-
-
-
ir
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
-
-
-
-
?
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
-, Q4PRC2
-
-
-
?
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
-
-
-
-
?
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
-
-
-
-
?
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
-
-
-
-
ir
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
-
-
-
-
?
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
-
-
-
-
?
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
-
-
-
-
?
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
-
-
-
-
?
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
-
-
-
-
ir
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
-
-
-
-
?
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
-
-
-
-
?
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
-
-
-
-
?
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
-, Q9AR41
-
-
-
?
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
Q9AR41
-
-
-
?
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
Q05329, Q99259
-
-
-
?
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
Q0GE18
-
-
-
ir
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
B2ZX20
-
-
-
?
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
-
-
-
-
?
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
Q99259
-
-
-
?
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
A9ZM78
-
-
-
?
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
B1B389, -
-
-
-
?
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
-, Q7XJB3
-
-
-
?
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
Q42521
-
-
-
?
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
A0EJ89, -
-
-
-
?
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
-
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
show the reaction diagram
-
GAD is the rate-limiting enzyme for GABA biosynthesis
-
-
?
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
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
show the reaction diagram
-
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
show the reaction diagram
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
show the reaction diagram
-
GAD is the rate-limiting enzyme in neurotransmitter gamma-aminobutyric acid, GABA, biosynthesis
-
-
?
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
-
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
show the reaction diagram
-
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
show the reaction diagram
-
GAD67 is the rate-limiting enzyme of GABA biosynthesis
-
-
?
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
-
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
show the reaction diagram
-
human glutamic acid decarboxylase 65 is a key autoantigen in type 1 diabetes
-
-
?
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
-
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
show the reaction diagram
-
the enzyme activity is higher in hippocampus of old rats compared to young rats
-
-
?
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
-
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
show the reaction diagram
Q0GE18
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
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
-
the reaction does not occur, when L-glutamate concentration is more than 4fold that of L-glutamine
-
-
?
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
Lactobacillus plantarum ATCC 14917
-
-
-
-
?
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
Lactobacillus brevis Lb85
-
-
-
-
?
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
Dugesia japonica SSP
-
-, GAD is the rate-limiting enzyme for GABA biosynthesis
-
-
?
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
Mus musculus BALB/c
-
-
-
-
?
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
Lactobacillus brevis CGMCC
-
-
-
-
ir
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
Lactobacillus brevis IFO12005
A9ZM78
-
-
-
?
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
Lactobacillus paracasei NFRI 7415
B1B389
-
-
-
?
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
-
-
-
-
?
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
Mus musculus B6D2
-
-
-
-
?
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
-
-
-
-
?
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
?
-
-
the activity is closely associated with its developmental status and may represent a link between differentiation events and energy metabolism
-
-
-
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
?
-
-
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
?
-
-
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
?
-
-
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
?
-
-
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
?
-
-
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, 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
?
-
-
GAD65 plays an essential role in neurotransmission, 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
?
-
-
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
?
-
-
susceptibility of GABAergic neurons or GAD transcript regulation within the context of ischemic injury to neocerebral cortex, overview
-
-
-
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
?
-
-
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
?
-
-
the recombinant engineered enzyme shows a broad substrate specificity
-
-
-
additional information
?
-
-
no activity with L-aspartate
-
-
-
additional information
?
-
Mus musculus BALB/c
-
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
?
-
-
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
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
L-Glu
4-Aminobutanoate + CO2
show the reaction diagram
-
rate-limiting enzyme involved in the synthesis of gamma-aminobutyric acid
-
-
?
L-Glu
?
show the reaction diagram
-
production of 4-aminobutanoate, which is the major inhibitory neurotransmitter in the mammalian brain
-
-
-
L-Glu
?
show the reaction diagram
-
isoenzyme GAD2 may play a unique role in nitrogen metabolism
-
-
-
L-Glu
?
show the reaction diagram
-
the enzyme is under the control of the asexual developmental cycle
-
-
-
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
-
-
-
-
?
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
-
-
-
-
?
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
-
-
-
-
?
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
-, Q4PRC2
-
-
-
?
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
-
-
-
-
?
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
-
-
-
-
?
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
-
-
-
-
ir
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
Q0GE18
-
-
-
ir
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
B2ZX20
-
-
-
?
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
A9ZM78
-
-
-
?
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
B1B389, -
-
-
-
?
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
-
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
show the reaction diagram
-
GAD is the rate-limiting enzyme for GABA biosynthesis
-
-
?
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
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
show the reaction diagram
-
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
show the reaction diagram
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
show the reaction diagram
-
GAD is the rate-limiting enzyme in neurotransmitter gamma-aminobutyric acid, GABA, biosynthesis
-
-
?
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
-
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
show the reaction diagram
-
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
show the reaction diagram
-
GAD67 is the rate-limiting enzyme of GABA biosynthesis
-
-
?
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
-
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
show the reaction diagram
-
human glutamic acid decarboxylase 65 is a key autoantigen in type 1 diabetes
-
-
?
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
-
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
show the reaction diagram
-
the enzyme activity is higher in hippocampus of old rats compared to young rats
-
-
?
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
-
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
show the reaction diagram
Dugesia japonica SSP
-
GAD is the rate-limiting enzyme for GABA biosynthesis
-
-
?
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
Mus musculus BALB/c
-
-
-
-
?
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
Lactobacillus brevis IFO12005
A9ZM78
-
-
-
?
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
Lactobacillus paracasei NFRI 7415
B1B389
-
-
-
?
L-glutamate
4-aminobutanoate + CO2
show the reaction diagram
Mus musculus B6D2
-
-
-
-
?
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
?
-
-
the activity is closely associated with its developmental status and may represent a link between differentiation events and energy metabolism
-
-
-
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
?
-
-
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
?
-
-
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
?
-
-
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
?
-
-
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
?
-
-
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, 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
?
-
-
GAD65 plays an essential role in neurotransmission, 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
?
-
-
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
?
-
-
susceptibility of GABAergic neurons or GAD transcript regulation within the context of ischemic injury to neocerebral cortex, overview
-
-
-
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
?
-
-
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
?
-
Mus musculus BALB/c
-
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
?
-
-
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
-
-
-
COFACTOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
Calmodulin
-
plus Ca2+, at pH 5.8, activates
Calmodulin
-
stimulation be Ca2+ plus calmodulin, no stimulation by Ca2+ or calmodulin alone
Calmodulin
-
Ca2+/calmodulin-dependent enzyme with calmodulin binding activity
Calmodulin
-
-
Calmodulin
-
-
Calmodulin
A0EJ89, -
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
-
tightly bound
pyridoxal 5'-phosphate
-
contains 2 mol of pyridoxal 5'-phosphate per mol of enzyme; Km: 0.02 mM
pyridoxal 5'-phosphate
-
dependent on
pyridoxal 5'-phosphate
-
activates up to 3.5times
pyridoxal 5'-phosphate
-
Km: 0.00005 mM
pyridoxal 5'-phosphate
-
highly specific as coenzyme
pyridoxal 5'-phosphate
-
Km: 0.00004 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
-
efficient non-covalent binding to the cofactor
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
-
forms an aldimine bond with Lys276
pyridoxal 5'-phosphate
-
Km-value 74 nM, wild-type, 490 nM, mutant with N-terminal deletion of 70 amino acids
pyridoxal 5'-phosphate
-
-
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
-
20% activity in absence
pyridoxal 5'-phosphate
-
no detectable activity in absence
pyridoxal 5'-phosphate
-
Km value 0.0017 mM
pyridoxal 5'-phosphate
-
slight conformational change upon binding to apo-enzyme
pyridoxal 5'-phosphate
-
-
pyridoxal 5'-phosphate
-
-
pyridoxal 5'-phosphate
-
-
pyridoxal 5'-phosphate
-
absolutely required
pyridoxal 5'-phosphate
B2ZX20
-
pyridoxal 5'-phosphate
-
; dependent on
pyridoxal 5'-phosphate
P69910
dependent on
pyridoxal 5'-phosphate
-, Q7XJB3
-
pyridoxal 5'-phosphate
Q42521
-
pyridoxal 5'-phosphate
-
-
pyridoxal 5'-phosphate
-
-
pyridoxal 5'-phosphate
-
-
pyridoxal 5'-phosphate
-
-
pyridoxal 5'-phosphate
-
-
pyridoxal 5'-phosphate
-
-
pyridoxal 5'-phosphate
-
-
pyridoxal 5'-phosphate
A0EJ89, -
-
pyridoxal 5'-phosphate
-
-
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
BaCl2
Q0GE18
activates by 22% at 5 mM
Ca2+
-
plus calmudulin, at pH 5.8, activates
Ca2+
-
stimulation by Ca2+ plus calmodulin, no stimulation by Ca2+ or calmodulin alone
Ca2+
-
Ca2+/calmodulin-dependent enzyme with calmodulin binding activity
Ca2+
B1B389, -
activates to 114% activity at 10 mM
Ca2+
Q9AR41
GAD activity is significantly enhanced in the presence of Ca2+
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+
A0EJ89, -
the addition of Ca2+ to the reaction mix causes an activation of GAD activity of 32%
Ca2+
-
maximum (174%) activity in the presence of 0.6 mM Ca2+
CoCl2
-
1 mM, activation to 128% of control
KBr
-
50 mM, enhances GAD activity in renal cortex homogenate
KCl
-
50 mM, enhances GAD activity in renal cortex homogenate
LiCl
-
50 mM, enhances GAD activity in renal cortex homogenate
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
NaBr
-
50 mM, enhances GAD activity in renal cortex homogenate
NaCl
-
50 mM, enhances GAD activity in renal cortex homogenate
NH4+
B1B389, -
activates to 132% activity at 10 mM
MnCl2
-
1 mM, activation to 133% of control
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
Q0GE18
MgCl2 and NaCl have no effect on enzyme activity
additional information
-
Mn2+ shows no effect on glutamate decarboxylase activity
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
(E)-pent-2-enoic acid
-
20% inhibition at 0.01 mg/ml
-
1-Methylimidazole
-
about 85% residual activity at 5 mM, about 77% residual activity at 10 mM, about 65% residual activity at 20 mM
2,6-pyridine dicarboxylic acid
-
-
2-mercaptoethanol
-
enzyme form I and II from embryos
2-mercaptoethanol
-
1 mM, 79% inhibition
2-Methyl-3,4-didehydroglutamic acid
-
-
2-oxoglutarate
-
-
2-oxoglutarate
-
-
2-oxoglutarate
-
-
3,4,5-Trihydroxybenzoic acid
-
weak
3,4,5-Trihydroxybenzoic acid
-
-
3,4,5-Trihydroxybenzoic acid
-
-
3,4-dihydroxybenzoic acid
-
weak
3,4-dihydroxybenzoic acid
-
-
3,4-dihydroxybenzoic acid
-
-
3,4-dihydroxyphenylacetic acid
-
-
3,5-Dihydroxybenzoic acid
-
weak
3,5-Dihydroxybenzoic acid
-
-
3-Bromopyruvate
-
-
3-Hydroxytyramine
-
-
3-Mercaptopropionic acid
-
-
3-Mercaptopropionic acid
-
-
3-Mercaptopropionic acid
-
-
3-Mercaptopropionic acid
-
-
3-Mercaptopropionic acid
-
-
3-Mercaptopropionic acid
-
; 43% inhibition at 0.1 mM
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
4,5-Dihydroxyisophthalic acid
-
weak
4,5-Dihydroxyisophthalic acid
-
-
4-aminobutanoate
-
-
4-Aminohex-5-ynoic acid
-
-
4-Bromoisophthalic acid
-
-
4-methylimidazole
-
about 75% residual activity at 5 mM, about 70% residual activity at 10 mM, about 58% residual activity at 20 mM
5,5'-dithiobis(2-nitrobenzoate)
-
-
5,5'-dithiobis(2-nitrobenzoate)
-
-
5,5'-dithiobis(2-nitrobenzoate)
-
-
5,5'-dithiobis(2-nitrobenzoate)
-
0.1 mM, 50.3% inhibition at pH 4.6, irreversible
acetate
-
-
Ag+
Q9AR41
58.3% residual activity at 2 mM
AgNO3
-
1 mM, 68% residual activity
AgNO3
Q0GE18
complete inhibition at 5mM
Al3+
Q9AR41
91.2% residual activity at 2 mM
allylglycine
-
-
Aminoethylylisothiouronium bromide
-
-
aminooxyacetic acid
-
-
asiaticoside
-
-
Asp
-
D-Asp, weak
ATP
-
in presence of leupeptin in freshly prepared homogenates. Inhibition of enzyme from homogenates stored without Triton X-100 for 24 h at 4C
Avidin
-
-
-
BaCl2
-
1 mM, 78% inhibition
beta-Methylene-DL-Asp
-
-
betulinic acid
-
27% inhibition at 0.01 mg/ml
bilobalide
-
-
CaCl2
-
1 mM, 31% inhibition
Carbohydrazide
-
-
CdCl2
-
1 mM, 38% inhibition
CH3COOH
Q9AR41
57.4% residual activity at 2 mM
Chelidamic acid
-
weak
Chelidamic acid
-
-
Chloroacetamide
-
no inhibition at pH 4.6, marked inhibition at pH 6.0 or higher
CoCl2
Q0GE18
62% inhibition at 5mM
CuCl2
-
1 mM, 43% inhibition
CuSO4
Q0GE18
93% inhibition at 5mM
Cycloglutamates
-
-
-
cyclosporin A
-
up to 0.3 mM, partial inhibition of activity in homogenate, but not in the supernatant obtained after centrifuging the homogenate
Cys
-
enzyme from embryos
D-erythro-4-fluoroglutamate
-
-
dithiothreitol
-
enzyme from embryos
dithiothreitol
-
1 mM, complete inhibition
DL-4-Amino-4-phosphonobutyrate
-
-
DL-alpha-Aminoadipic acid
-
-
DL-alpha-Methylglutamate
-
-
DL-Penicillamine
-
-
DL-Penicillamine
-
-
EDTA
-
1 mM, 77% inhibition
EDTA
Q9AR41
91.2% residual activity at 2 mM
EGTA
-
0.5 mM, 20% inhibition
Fe2+
-
-
-
FeCl3
-
1 mM, 65% inhibition
FeSO4
Q0GE18
92% inhibition at 5mM
ginsenosides
-
23% inhibition at 0.01 mg/ml, ethanol extract of Panax quinquefolius, different glycoside derivatives, overview
-
Glutamate gamma-hydroxamate
-
weak
Glutarate
-
-
Glutarate
-
inhibits 42% at 1 mM
Hg2+
Q9AR41
37.7% residual activity at 2 mM
HgCl2
-
0.01 mM, 80.1% inhibition at pH 4.6, irreversible
HgCl2
-
1 mM, 89% inhibition
HgCl2
-
1 mM, 31.5% residual activity
hydroxylamine
-
-
isoniazide
B2ZX20
isoniazide-induced seizures are mediated primarily through competition with the cofactor pyridoxal 5'-phosphate resulting in the inhibition of GAD activity
Isonicotinic acid hydrazide
-
-
KI
-
1 mM, 55% residual activity
L-Asn
-
inhibits 4% at 1 mM
L-Asp
-
inhibits 20% at 1 mM
L-aspartate beta-hydroxamate
-
weak
L-Cysteine hydrochloride
-
-
L-cysteine sulfinic acid
-
-
L-erythro-4-fluoroglutamate
-
-
L-Glu
-
substrate inhibition at high concentrations
L-Glu
-
weak
L-Glu
-
inhibits 25% at 1 mM
L-Thiomalic acid
-
-
malate
-
weak
Mercaptosuccinic acid
-
-
Mg2+
Q9AR41
90.1% residual activity at 2 mM
MgCl2
-
1 mM, 46% inhibition
Mn2+
Q9AR41
92.6% residual activity at 2 mM
Na2SO4
Q0GE18
10% inhibition at 5mM
NaCl
B1B389, -
61.5% inhibition at 10 mM
NEM
-
no inhibition at pH 4.6, marked inhibition at pH 6.0 or higher
p-hydroxymercuribenzoate
-
-
p-hydroxymercuribenzoate
-
-
Pb(CH3COO)2
-
1 mM, 37% inhibition
PCMB
-
0.1 mM, 68.5% inhibition at pH 4.6, irreversible
Phenylglyoxal
-
-
reduced glutathione
-
enzyme from embryos
SDS
-
1 mM, 26% inhibition
SDS
Q9AR41
66.9% residual activity at 40 mM
Semicarbazide
-
-
Substituted dicarboxylic acids
-
-
-
Thiocarbohydrazide
-
-
Thioglycollic acid
-
-
Thiomalate
-
-
Thiosemicarbazide
-
-
ursolic acid
-
; 11.2% inhibition at 0.01 mg/ml
valerenic acid
-
20% inhibition at 0.01 mg/ml
Zinc acetate
-
-
ZnCl2
-
1 mM, 37% inhibition
ZnSO4
Q0GE18
80.4% inhibition at 5mM
MnSO4
Q0GE18
88% inhibition at 5mM
additional information
-
-
-
additional information
-
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
-
additional information
-
enzyme inhibition by glutamic acid decarboxylase autoantibodies, overview
-
additional information
-
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
-
additional information
Q0GE18
poor inhibition by LiCl, CaCl2, and KCl. MgCl2 and NaCl have no effect on enzyme activity
-
additional information
-
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%)
-
additional information
-
chronic mild stress leads to 60% reduced enzyme activity in old rats, which is reversible by neuronal nitric oxide synthase inhibitor 7-nitroindazole, overview
-
additional information
-
downregulation of reelin and GAD67 expression by the increase of DNA-methyltransferase 1-mediated hypermethylation of promoters in GABAergic interneurons of the telencephalon
-
additional information
-
identification of inhibitory antibodies, overview
-
additional information
-
the glutamate decarboxylase activity of p42 is not inhibited by high concentrations of Mn2+
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
(NH4)2SO4
-
activates
2-oxoglutarate
-
stimulates
3-Mercaptopropionic acid
-
-
5,5'-dithiobis(2-nitrobenzoic acid)
-
stimulates
ADP
-
2 mM, activation to about 170% of control without detergent. Activation to about 210% of control in presence of 1% Triton X-100
aminooxyacetic acid
-
-
ammonium sulfate
A9ZM78
at 1.8 M
AMP
-
2 mM, activation to about 125% of control without detergent. Activation to about 140% of control in presence of 1% Triton X-100
apocalmodulin
-
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
-
asiaticoside
-
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
-
2 mM, activation to about 150% of control in presence of 1% Triton, inhibition to 20% of control without detergent
bilobalide
-
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
Br-
-
activates
Ca2+
Q5F1L4
48% activation, up to 200% activation in presence of both Ca2+ and calmodulin
Ca2+
-
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
CaCl2
-
0.5 mM, pH 5.6, 45% increase in activity
Calmodulin
Q5F1L4
42% activation, up to 200% activation in presence of both Ca2+ and calmodulin
Calmodulin
-
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
Q42521
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
-
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
Cl-
-
activates
CTP
-
2 mM, activation to about 110% of control without detergent. Activation to about 200% of control in presence of 1% Triton X-100
EDTA
-
2 mM, stimulates
F-
-
activates
Glutarate
-
stimulates
GTP
-
2 mM, activation to about 125% of control without detergent. Activation to about 190% of control in presence of 1% Triton X-100
I-
-
activates
UTP
-
2 mM, activation to about 140% of control without detergent. Activation to about 190% of control in presence of 1% Triton X-100
L-Gln
-
activates 18% at 1 mM
additional information
-
6-azauracil and Phe decrease specificity for L-Glu and increased specificity to L-Asp
-
additional information
-
a model to link neuronal excitation and activation of L-glutamate decarboxylase by Ca2+-dependent phosphatase
-
additional information
A9ZM78
sodium glutamate is essential for tetramer formation and its activation
-
additional information
-
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
-
additional information
-
AD67 immunoreactivity in the hippocampal CA1 region is significantly increased 24 h after ischemia/reperfusion
-
additional information
-
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
-
additional information
B2ZX20
increased GAD expression in taurine-fed mice
-
additional information
-
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
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
5.2
-
cysteine sulfinic acid
-
-
1.04
-
L-alpha-Methylglutamate
-
pH 4.6, 25C
5.4
-
L-cysteic acid
-
-
0.174
-
L-Glu
-
enzyme form alpha
0.451
-
L-Glu
-
enzyme form beta
0.5
1.7
L-Glu
-
from pH 5.8 to pH 7.8 the Km decreases from 1.7 mM at pH 5.8 to 0.5 mM at pH 7.8
0.5
1.9
L-Glu
-
at pH 4.6
0.6
-
L-Glu
-
pH 7.8
0.7
-
L-Glu
-
-
1.15
-
L-Glu
-
pH 5.0, 37C
1.237
-
L-Glu
-
gamma-form
1.28
-
L-Glu
-
pH 6.8
1.3
-
L-Glu
-
-
1.3
-
L-Glu
-
6*His-tagged GAD67, crude extract; GAD65 after cleavage with protease factor Xa
1.37
-
L-Glu
-
-
1.4
-
L-Glu
-
6*His-tagged GAD65; GAD67 after cleavage with protease factor Xa
1.59
-
L-Glu
-
-
1.6
-
L-Glu
-
-
2.2
-
L-Glu
-
-
2.5
-
L-Glu
-
GAD67-GST fusion protein expressed in Escherichia coli
2.7
-
L-Glu
-
-
2.9
-
L-Glu
-
GAD65-GST fusion protein expressed in Escherichia coli
3.2
-
L-Glu
-
-
5.6
-
L-Glu
-
-
8.3
-
L-Glu
-
-
22
-
L-Glu
-
-
0.0274
-
L-glutamate
Q9AR41
-
0.18
-
L-glutamate
-
isoform GAD67, treated with trypsin, which also increases vmax value by 31%
0.3
-
L-glutamate
-
isoform GAD67
0.5
-
L-glutamate
-
mutant with N-terminal deletion of 90 amino acids, pH 7.2
0.67
-
L-glutamate
-
isoform GAD67, lacking aminoterminal 70 amino acids, presence of apocalmodulin
0.69
-
L-glutamate
-
mutant with N-terminal deletion of 70 amino acids, pH 7.2
0.69
-
L-glutamate
-
isoform GAD67, lacking aminoterminal 70 amino acids; isoform GAD67, presence of apocalmodulin
0.71
-
L-glutamate
-
wild-type, pH 7.2
0.71
-
L-glutamate
-
isoform GAD67
1
-
L-glutamate
A9ZM78
pH 4.6, 37C, native enzyme
1.33
-
L-glutamate
-
isoform GAD65, treated with trypsin, which also increases vmax value by 33%
1.4
-
L-glutamate
A9ZM78
pH 4.6, 37C, recombinant enzyme
1.44
-
L-glutamate
-
isoform GAD65
1.51
-
L-glutamate
P69910
mutant enzyme H465A, in 0.2 M pyridine/HCl buffer, pH 4.6, at 37C
1.61
-
L-glutamate
P69910
mutant enzyme DELTAHT, in 0.2 M pyridine/HCl buffer, pH 4.6, at 37C
1.9
-
L-glutamate
-
recombinant enzyme, in acetate buffer (20 mM, pH 4.8), at 40C
2.2
-
L-glutamate
-
in 0.2 M phosphate buffer (pH 7.0) containing 0.1 mM pyridoxal 5'-phosphate, at 25C
2.3
-
L-glutamate
Q0GE18
pH 4.0, 40C
2.32
-
L-glutamate
P69910
wild type enzyme, in 0.2 M pyridine/HCl buffer, pH 4.6, at 37C
5
-
L-glutamate
B1B389, -
pH 5.0, 37C
32.3
-
L-glutamate
-
pH 5.6, 40C
additional information
-
additional information
-
Km-values depending on buffer
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
9.53
-
L-alpha-Methylglutamate
-
pH 4.6, 25C
0.41
-
L-Glu
-
GAD65 after cleavage with protease factor Xa
1.8
-
L-Glu
-
6*His-tagged GAD65; GAD65-GST fusion protein expressed in Escherichia coli
6.2
-
L-Glu
-
GAD67 after cleavage with protease factor Xa
7
-
L-Glu
-
-
7.7
-
L-Glu
-
GAD67-GST fusion protein expressed in Escherichia coli
16.24
-
L-glutamate
P69910
mutant enzyme DELTAHT, in 0.2 M pyridine/HCl buffer, pH 4.6, at 37C
20.75
-
L-glutamate
P69910
mutant enzyme H465A, in 0.2 M pyridine/HCl buffer, pH 4.6, at 37C
24.85
-
L-glutamate
P69910
wild type enzyme, in 0.2 M pyridine/HCl buffer, pH 4.6, at 37C
kcat/KM VALUE [1/mMs-1]
kcat/KM VALUE [1/mMs-1] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
10.08
-
L-glutamate
P69910
mutant enzyme DELTAHT, in 0.2 M pyridine/HCl buffer, pH 4.6, at 37C
12211
10.71
-
L-glutamate
P69910
wild type enzyme, in 0.2 M pyridine/HCl buffer, pH 4.6, at 37C
12211
13.74
-
L-glutamate
P69910
mutant enzyme H465A, in 0.2 M pyridine/HCl buffer, pH 4.6, at 37C
12211
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.5
-
NO
-
pH 7.3, 25C, GAD65, recombinant enzyme expressed in Escherichia coli; pH 7.3, 25C, GAD67, recombinant enzyme expressed in Escherichia coli
0.29
-
O2
-
pH 7.3, 25C, GAD67, recombinant enzyme expressed in Escherichia coli
0.46
-
O2
-
pH 7.3, 25C, GAD56, recombinant enzyme expressed in Escherichia coli
IC50 VALUE [mM]
IC50 VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0123
-
3-Mercaptopropionic acid
-
; at 37C; at 37C, pH not specified in the publication
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0.0011
-
-
purified native enzyme
0.009
-
-
crude extract, in 50 mM PBS buffer, pH 5.6, at 40C
0.039
-
-
mutant with N-terminal deletion of 70 amino acids, pH 7.2
0.041
-
-
mutant with N-terminal deletion of 90 amino acids, pH 7.2
0.216
-
-
wild-type, pH 7.2
0.462
-
-
-
1.37
-
-
-
1.85
-
-
GAD67
1.96
-
-
GAD65
2.57
-
-
-
2.76
-
-
-
2.956
-
-
-
3.25
-
-
-
7.666
-
-
after 851.7fold purification, in 50 mM PBS buffer, pH 5.6, at 40C
7.68
-
Q9AR41
-
15
-
Q9AR41
wild-type, pH 7.0, 30C, absence of Ca2+/calmodulin
16.7
-
B1B389, -
purified recombinant enzyme
17.3
-
Q9AR41
wild-type, pH 7.0, 30C, presence of Ca2+/calmodulin
67.9
-
-
-
103.5
-
Q0GE18
purified enzyme
148.4
-
-
-
197
-
Q9AR41
wild-type, pH 6.0, 30C, presence of Ca2+/calmodulin
199
-
Q9AR41
wild-type, pH 6.0, 30C, absence of Ca2+/calmodulin
223.4
-
-
pH 5.6, 40C
605
-
Q9AR41
mutant lacking 31 C-terminal amino acids, pH 7.0, 30C, presence of Ca2+/calmodulin
641
-
Q9AR41
mutant lacking 31 C-terminal amino acids, pH 7.0, 30C, absence of Ca2+/calmodulin
685
-
Q9AR41
wild-type, pH 5.0, 30C, absence of Ca2+/calmodulin
710
-
Q9AR41
wild-type, pH 5.0, 30C, presence of Ca2+/calmodulin
2719
-
Q9AR41
mutant lacking 31 C-terminal amino acids, pH 6.0, 30C, presence of Ca2+/calmodulin
2775
-
Q9AR41
mutant lacking 31 C-terminal amino acids, pH 6.0, 30C, absence of Ca2+/calmodulin
4670
-
Q9AR41
mutant lacking 31 C-terminal amino acids, pH 5.0, 30C, absence of Ca2+/calmodulin
4850
-
Q9AR41
mutant lacking 31 C-terminal amino acids, pH 5.0, 30C, presence of Ca2+/calmodulin
additional information
-
-
-
additional information
-
-
-
additional information
-
-
-
additional information
-
-
-
additional information
-
-
radiometric assay
additional information
-
-
-
additional information
-
-
-
additional information
-
-
-
additional information
-
-
enzyme activity in hippocampi of young and old rats
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
3.8
4.6
P69910
at mildly alkaline pH GadB is inactive
4
-
-
activity in conidia
4.2
4.6
A9ZM78
native enzyme
4.5
5
A9ZM78
recombinant His-tagged enzyme
5.5
5.8
-
-
5.5
-
Q42521
maximal turnover in the absence of calmodulin
5.5
-
Q9AR41
-
5.6
-
-
-
5.8
-
-
-
5.8
-
A0EJ89, -
-
6
-
Q42521
maximum activity at about pH 6
6.4
6.5
-
-
6.6
-
-
-
6.8
-
-
-
7
7.5
-
broad
7
-
-
-
7
-
-
-
7.4
-
-
-
8
-
-
recombinant engineered enzyme
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
3.3
5.8
-
pH 3.3: about 20% of maximal activity, pH 3.5: about 65% of maximal activity, pH 5.2: about 55% of maximal activity, pH 5.8: about 20% of maximal activity
3.5
5.2
Q0GE18
pH 3.5: about 40% of maximal activity, pH 4.5: about 65% of maximal activity, pH 5.0: about 50% of maximal activity pH 5.2: about 40% of maximal activity
3.5
6
B1B389, -
-
4
6.5
-
pH 4.0: about 75% of maximal activity, pH 6.5: about 55% of maximal activity
4
-
-
40% residual activity
4.5
6
-
pH 4.5: about 50% of maximal activity, pH 6.0: about 75% of maximal activity
4.5
7
-
about 25% of maximal activity at pH 4.5 and pH 7.0
5
9
Q9AR41
retains 80% of its original activity in the pH range 5-9
5.2
7.8
-
pH 5.2: about 55% of maximal activity, pH 7.8: about 35% of maximal activity
6
7.5
-
pH 6.0: about 80% of maximal activity, pH 7.5: about 65% of maximal activity
6
7.8
-
pH 6.0: about 65% of maximal activity, pH 7.8: about 35% of maximal activity
6.4
7.8
-
pH 6.4: about 50% of maximal activity, pH 7.8: about 70% of maximal activity
9
-
-
20% residual activity
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
30
-
-
activity in conidia
30
-
A9ZM78
native enzyme
37
42
-
GAD65-GST fusion protein expressed in Escherichia coli
37
-
-
assay at
39
43
-
6*His-tagged GAD65; GAD65 after cleavage with protease factor Xa
40
-
-
-
40
-
Q9AR41
-
43
50
-
6*His-tagged GAD67, crude extract; GAD67-GST fusion protein expressed in Escherichia coli
45
50
-
GAD67 after cleavage with protease factor Xa
97
-
-
above, recombinant engineered enzyme
TEMPERATURE RANGE
TEMPERATURE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
15
42
-
15C: 65% of maximal activity, 42C: about 55% of maximal activity
30
50
Q9AR41
retains 78 and 69% of its maximum activity at 30 and 50C, respectively
40
80
Q0GE18
about 40% of maximal activity at 40C and 80C
60
-
-
13% residual activity
pI VALUE
pI VALUE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5.4
-
-
calculated from amino acid sequence
5.7
-
-
calculated from amino acid sequence
5.7
-
A0EJ89, -
calculated from amino acid sequence
6.8
-
-
at the position of 42 kDa four protein spots with the pI-values 6.8, 6.9, 7.1, and 7.3 are found, isoelectric focusing
6.9
-
-
at the position of 42 kDa four protein spots with the pI-values 6.8, 6.9, 7.1, and 7.3 are found, isoelectric focusing
7.1
-
-
at the position of 42 kDa four protein spots with the pI-values 6.8, 6.9, 7.1, and 7.3 are found, isoelectric focusing
7.3
-
-
at the position of 42 kDa four protein spots with the pI-values 6.8, 6.9, 7.1, and 7.3 are found, isoelectric focusing
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
basolateral
Manually annotated by BRENDA team
-
areas implicated in agression control including anterior hypothalamus, medial and central amygdaloid nuclei, lateral septum
Manually annotated by BRENDA team
-
both full length enzyme and a shorter form with aminoterminal deletion
Manually annotated by BRENDA team
-
enzyme transcripts are detected largely in medial and ventral regions of telencephalon, nucleus preopticus, nucelus recessus lateralis of the hypothalamus, and Purkinje cell layer of the cerebellum. GABA-transamainase activity is significanlty higher than total glutamic acid decarboxylase activity in the brain
Manually annotated by BRENDA team
-
fetal brain: GAD67, adult brain: GAD67 and GAD65
Manually annotated by BRENDA team
-
somatosensory cortex
Manually annotated by BRENDA team
Q05329, Q99259
;
Manually annotated by BRENDA team
-
immunoreactive neurons in the hippocampal CA1 region at various age stages, in 1-year-old dogs in the stratum oriens, in 6-year-old dogs in the CA1 region, but scarcely found in the CA1 region in 10-year-old dogs
Manually annotated by BRENDA team
Mus musculus B6D2, Mus musculus BALB/c
-
-
-
Manually annotated by BRENDA team
Q99259
anterior cingulate cortex and superior temporal brain cortex
Manually annotated by BRENDA team
-
Purkinje cells and cerebellar cortex
Manually annotated by BRENDA team
-
cerebrospinal fluid elicits physiopathological effects on cerebellar GABA synapses in vitro, cerebrospinal fluid IgG-induced depressive effects are abolished by absorption of GAD-antibodies using recombinant GAD. Furthermore, forskolin, an activator of cAMP, recovers the cerebrospinal fluid IgG-induced reduction of GABA release
Manually annotated by BRENDA team
-
cerebellar dentate nuclei
Manually annotated by BRENDA team
Mus musculus BALB/c
-
-
-
Manually annotated by BRENDA team
-
germination of conidia in the submerged culture leads to temporary decrease in GAD activity. After prolonged cultivation, the activity displays quasi-oscillatory changes. High activity in the stationary phase
Manually annotated by BRENDA team
-
the enzyme is most abundantly expressed in the corn ears
Manually annotated by BRENDA team
-
2 enzyme form: I and II
Manually annotated by BRENDA team
-
glutamic acid decarboxylase in E18 embryonic hippocampal neurons
Manually annotated by BRENDA team
-
initial segment
Manually annotated by BRENDA team
-
glutamic acid decarboxylase in E18 embryonic hippocampal neurons
Manually annotated by BRENDA team
-
the enzyme activity is higher in hippocampus of old rats compared to young rats
Manually annotated by BRENDA team
-
intraperitoneal treatment with gamma-aminobutanaote B agonist baclofen reduces mRNA levels of isoform GAD67 approximately 2fold and gamma-aminobutanaote transaminase approximately 2fold
Manually annotated by BRENDA team
-
isoform GAD65, mainly in middle and upper portions of villi, GAD65 is not found in goblet cells, and GAD67 is not detected in jejunum at all
Manually annotated by BRENDA team
-
the renal enzyme differs from the brain and pancreatic enzyme by its strong binding to membranes that is not influenced by detergents
Manually annotated by BRENDA team
-
mononuclear leukocyte, isoform GAD65 is expressed with its C-terminal end truncated
Manually annotated by BRENDA team
-
nerve terminal
Manually annotated by BRENDA team
-
including brain and ventral nerve cords, distribution pattern of GAD protein and mRNA, dotted expression pattern, a few cells located in both the head and pharynx regions express DjGAD mRNA, overview
Manually annotated by BRENDA team
-
two isoforms ofGAD, GAD67and GAD65
Manually annotated by BRENDA team
Dugesia japonica SSP
-
including brain and ventral nerve cords, distribution pattern of GAD protein and mRNA, dotted expression pattern, a few cells located in both the head and pharynx regions express DjGAD mRNA, overview
-
Manually annotated by BRENDA team
-
in lateral reticular nucleus of thalamus, co-localization of glutamate decarboxylase and phosphate-activiated glutaminase within most neuronal cell bodies
Manually annotated by BRENDA team
-
glutamic acid decarboxylase in E18 embryonic hippocampal neurons
Manually annotated by BRENDA team
Q05329, Q99259
;
Manually annotated by BRENDA team
-
GABAergic neurons
Manually annotated by BRENDA team
-
DjGAD-immunopositive neurons in the anterior region, distribution pattern of GAD protein and mRNA, dotted expression pattern, a few cells located in both the head and pharynx regions express DjGAD mRNA, overview
Manually annotated by BRENDA team
-
Purkinje and GABAergic dentate neurons
Manually annotated by BRENDA team
-
GABAergic neurons, non-pyramidal cells of types A-C, and principal cells
Manually annotated by BRENDA team
-
GABAergic interneuron
Manually annotated by BRENDA team
Dugesia japonica SSP
-
DjGAD-immunopositive neurons in the anterior region, distribution pattern of GAD protein and mRNA, dotted expression pattern, a few cells located in both the head and pharynx regions express DjGAD mRNA, overview
-
Manually annotated by BRENDA team
-
of the hypothalamus, isoform GAD65 is significantly more abundant than isoform GAD67
Manually annotated by BRENDA team
Rattus norvegicus LEW-1A
-
-
-
Manually annotated by BRENDA team
-
part of olfactory cortex
Manually annotated by BRENDA team
-
orbitofrontal, anterior cingulate, and dorsolateral
Manually annotated by BRENDA team
-
1 enzyme form
Manually annotated by BRENDA team
Q5F1L4
mainly in root of seedling grown under phosphorous deprivation conditions
Manually annotated by BRENDA team
A0EJ89, -
highest expression
Manually annotated by BRENDA team
Q5F1L4
of non-germinated brown rice
Manually annotated by BRENDA team
-, Q7XJB3
germinating seed, GAD1 protein is observed in seeds of various states such as developing, matured and soaking
Manually annotated by BRENDA team
Q5F1L4
mainly in root of seedling grown under phosphorous deprivation conditions
Manually annotated by BRENDA team
Rattus norvegicus LEW-1A
-
enzyme degradation kinetics
-
Manually annotated by BRENDA team
-
highest expression
Manually annotated by BRENDA team
-
intraperitoneal treatment with gamma-aminobutanaote A agonist muscimol decreases mRNA of isoform GAD65 approximately 10fold, gamma-aminobutanaote transaminase approximately 15fold and tyrosine hydroxylase approximately 3fold
Manually annotated by BRENDA team
-
the 58-kDa GAD65, N-terminal 69 amino acids truncated form of full-length GAD65 protein, is developmentally expressed during post-natal testis maturation
Manually annotated by BRENDA team
-
lateral reticular nucleus of thalamus, co-localization of glutamate decarboxylase and phosphate-activiated glutaminase within most neuronal cell bodies
Manually annotated by BRENDA team
additional information
-
spleen from Dasypus novemcinctus infected with Mycobacterium leprae
Manually annotated by BRENDA team
additional information
-
quantitative immunohistochemic analysis GAD-immunoreactive neuropils of GAD65 and GAD67 isozymes in brains of depressed and healthy individuals, overview
Manually annotated by BRENDA team
additional information
-
GAD67 tissue expression pattern in exercised and nonexercised rats, overview
Manually annotated by BRENDA team
additional information
Q05329, Q99259
GAD67 is evenly distributed throughout the cell
Manually annotated by BRENDA team
additional information
-
GAD67 is evenly distributed throughout the cell
Manually annotated by BRENDA team
additional information
-
immunohistochemic analysis of isozyme distributions, overview
Manually annotated by BRENDA team
additional information
-
GAD65, GAD67, PPD and vGAT mRNA levels in the striatum and GABAA receptor alpha1 subunit mRNA levels in the substantia nigra, pars reticulata, and striatum in rats with single or subchroninc application of unilateral 6-hydroxydopamine lesion, overview
Manually annotated by BRENDA team
additional information
-
localization study, overview
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
Q05329, Q99259
-
Manually annotated by BRENDA team
-
localized exclusively in cytoplasm at neutral pH, but is recruited to the membrane when the pH falls
Manually annotated by BRENDA team
-
more than 90% of GAD activity occurs in the cytosolic fraction. Isoform GAD67 is exclusively expressed in the cytosolic fraction
Manually annotated by BRENDA team
Q05329, Q99259
palmitoylated GAD65 co-localizes with Rab5 in Golgi membranes and axons, and Rab5 regulates the trafficking of palmitoylated GAD65 from Golgi membranes to axons in an endosomal trafficking pathway
Manually annotated by BRENDA team
-
palmitoylated GAD65 co-localizes with Rab5 in Golgi membranes and axons, and Rab5 regulates the trafficking of palmitoylated GAD65 from Golgi membranes to axons in an endosomal trafficking pathway
Manually annotated by BRENDA team
Q05329, Q99259
palmitoylated GAD65 co-localizes with Rab5 in Golgi membranes and axons, and Rab5 regulates the trafficking of palmitoylated GAD65 from Golgi membranes to axons in an endosomal trafficking pathway
Manually annotated by BRENDA team
-
palmitoylated GAD65 co-localizes with Rab5 in Golgi membranes and axons, and Rab5 regulates the trafficking of palmitoylated GAD65 from Golgi membranes to axons in an endosomal trafficking pathway
Manually annotated by BRENDA team
-
bound to, highest specific activity is present in mitochondrial/vacuolar organellar fraction
Manually annotated by BRENDA team
-
localized exclusively in cytoplasm at neutral pH, but is recruited to the membrane when the pH falls
Manually annotated by BRENDA team
-
the renal enzyme differs from the brain and pancreatic enzyme by its strong binding to membranes that is not influenced by detergents
Manually annotated by BRENDA team
-
three distinct moieties of glutamate decarboxylase localize to membrane compartments, an amphiphilic GAD65 homodimer, an amphiphilic GAD65/67 heterodimer, tethered to membranes via the GAD65 subunit and a hydrophilic GAD67 homodimer, which associates with membranes by a distinct mechanism
Manually annotated by BRENDA team
-
the enzyme can become membrane-associated though interactions with a member of the heat shock protein 70 family, heat shock cognate 70, which is then anchored to synaptic vesicles through interactions with an intrinsic synaptic vesicle protein, cysteine string protein
Manually annotated by BRENDA team
-
targeting of the processed enzyme
Manually annotated by BRENDA team
-
isoform GAD65 is localized to the membrane fraction
Manually annotated by BRENDA team
-
external surface of mitochondrion
Manually annotated by BRENDA team
additional information
Q05329, Q99259
GAD67 is evenly distributed throughout the cell
-
Manually annotated by BRENDA team
additional information
-
subcellular localization study, overview
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
30500
-
-
gel filtration
42000
-
-
SDS-PAGE
43000
-
-
gel filtration
48000
-
Q9AR41
SDS-PAGE
56100
-
-
calculated from amino acid sequence
57000
-
-, Q7XJB3
SDS-PAGE
58000
-
-
SDS-PAGE, N-terminal 69 amino acids truncated form of full-length GAD65 protein
65000
-
-
SDS-PAGE
65000
-
-
full-length GAD65 protein, SDS-PAGE
66000
-
-
gel filtration
78000
-
-
gel filtration
85000
-
-
high speed sedimentation equilibrium
86000
-
-
gel filtration
91000
-
-
gel filtration
100000
-
-
gel filtration
103600
-
Q0GE18
gel filtration
110000
-
-
gel filtration
110000
-
-
nondenaturing PAGE
110000
-
A9ZM78
recombinant enzyme, pH 7.0, gel filtration
110000
-
B1B389, -
gel filtration
110000
-
-
gel filtration
118000
-
-
nondenaturing PAGE
120000
-
-
gradient PAGE
120000
-
-
enzyme form II from embryo, sucrose density gradient centrifugation
120000
-
-
gel filtration
140000
-
-
nondenaturing PAGE
153000
-
-
gel filtration
220000
-
-
equilibrium sedimentation
256000
-
-
enzyme form I from embryo, sucrose density gradient centrifugation
300000
-
-
gel filtration
300000
-
-
gel filtration, absence of Ca2+/calmodulin
310000
-
-
equilibrium sedimentation
310000
-
-
root enzyme
310000
-
Q42521
static light-scattering
340000
-
-
gel filtration
342000
-
Q42521
calculated from amino acid sequence
580000
-
-
gel filtration, absence of Ca2+/calmodulin
680000
-
-
gel filtration, presence of Ca2+/calmodulin
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 40000, SDS-PAGE in presence of 4 M urea and 2-mercaptoethanol; x * 40000 + x * 80000, SDS-PAGE
?
-
x * 51350, SDS-PAGE
?
-
x * 56000, isoenzyme GAD2, SDS-PAGE; x * 58000, isoenzyme GAD1, SDS-PAGE
?
Q5F1L4
x * 56000-58000, SDS-PAGE
?
-
x * 52500, SDS-PAGE, x * 52000, calculated
?
-
x * 65000, SDS-PAGE
?
-
x * 53000, SDS-PAGE
?
-
x * 67000, SDS-PAGE
?
-
x * 56200, calculated from amino acid sequence; x * 61000, His-tagged enzyme, SDS-PAGE
?
A0EJ89, -
x * 56000, SDS-PAGE; x * 57200, calculated from amino acid sequence
?
Lactobacillus plantarum ATCC 14917
-
x * 53000, SDS-PAGE
-
dimer
-
2 * 43000, SDS-PAGE
dimer
-
2 * 67000, SDS-PAGE
dimer
-
2 * 44000, high speed equilibrium sedimentation after treatment with 6 M guanidine HCl and 0.1 M beta-mercaptoethanol
dimer
-
2 * 59000, SDS-PAGE
dimer
-
2 * 60000, SDS-PAGE
dimer
-
2 * 74000, SDS-PAGE
dimer
-
dimer-forming interactions are mediated mainly by carboxyl-terminal domain
dimer
-
crystallization data
dimer
-
2 * 40000, SDS-PAGE
dimer
A9ZM78
2 * 54000, inactive, recombinant His-tagged enzyme, SDS-PAGE
dimer
B1B389, -
2 * 57000, SDS-PAGE
dimer
Q0GE18
2 * 46900, SDS-PAGE
dimer
Lactobacillus brevis IFO12005
-
2 * 54000, inactive, recombinant His-tagged enzyme, SDS-PAGE
-
dimer
Lactobacillus paracasei NFRI 7415
-
2 * 57000, SDS-PAGE
-
hexamer
-
6 * 50000
hexamer
-
6 * 58000, SDS-PAGE, gel filtration in presence of SDS
hexamer
-
-
hexamer
-
6 * 48000, SDS-PAGE
homodimer
-
gel filtration
homohexamer
Q42521
X-ray crystallography, 6 * 57066, amino acid sequence
homooctamer
-
native PAGE
homotetramer
-
native PAGE
monomer
-
1 * 33200, SDS-PAGE
oligomer
-
x * 58000, SDS-PAGE of full-length enzyme
tetramer
A9ZM78
4 * 54000, ammonium sulfate-activated, recombinant His-tagged enzyme, SDS-PAGE
tetramer
Lactobacillus brevis IFO12005
-
4 * 54000, ammonium sulfate-activated, recombinant His-tagged enzyme, SDS-PAGE
-
monomer
-
1 * 42000, SDS-PAGE
additional information
-
both isoform GAD65 and GAD67 in vivo build up a protein complex with apocalmodulin
additional information
-
N-terminal segments of both GAD65 and GAD67 are exposed and flexible
additional information
Q9AR41
the C-terminal extension of enzyme plays a role as a strong autoinhibitory domain. Truncation causes the enzyme to act constitutively, with higher activity than wild-type both in vitro and in vivo
additional information
A9ZM78
sodium glutamate is essential for tetramer formation and its activation
additional information
-
mapping of T cell epitopes on GAD65, overview
additional information
Q05329, Q99259
25 and 44 kDa GAD through differential GAD67 RNA splicing, the 25 kDa is enzymatically inactive and is present usually early in the development, the 44 kDa GAD is enzymatically active
additional information
-
25 and 44 kDa GAD through differential GAD67 RNA splicing, the 25 kDa is enzymatically inactive and is present usually early in the development, the 44 kDa GAD is enzymatically active
additional information
Lactobacillus brevis IFO12005
-
sodium glutamate is essential for tetramer formation and its activation
-
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
phosphoprotein
-
isoform GAD65 is activated by phosphorylation, GAD67 is inhibited by phosphorylation. Phosphorylation of GAD67 occurs at T91
phosphoprotein
Q05329, Q99259
protein kinase A is responsible for phosphorylation and inhibition of GAD67 activity, while calcineurin is the phosphatase responsible for dephosphorylation and activation of GAD67
proteolytic modification
-
the purified recombinant GAD67 is cleaved by mu-calpain at specific sites in Ca2+-dependent manner. In brain synaptosomal preparation, GAD67 is cleaved to its truncated form by an endogenous protease which is inhibited by specific calpain inhibitors. In mu-calpain knockout mice, the level of tGAD in the brain is greatly reduced compared with the wild type. When mu-calpain gene is silenced by siRNA, the level of tGAD is also markedly reduced compared to the control group. Mu-calpain is activated by neuronal stimulation and Ca2+-influx. Calpastatin inhibits GAD67 processing, overview
proteolytic modification
Q05329, Q99259
conversion of full-length GAD65 to truncated GAD65 is not the result of random post-mortem degradation, but that it is an intracellular process that is highly regulated. The cleavage is mediated by calpain, a Ca2+-dependent cysteine protease
lipoprotein
-
palmitoylation of cysteines 30 and 45 is critical for post-Golgi trafficking of GAD65 to presynaptic sites and for its relative dendritic exclusion, leading to the presynaptic clustering of GAD65
phosphoprotein
-
protein kinase A is responsible for phosphorylation and inhibition of GAD67 activity, while calcineurin is the phosphatase responsible for dephosphorylation and activation of GAD67
proteolytic modification
-
the purified recombinant GAD67 is cleaved by mu-calpain at specific sites in Ca2+-dependent manner. In brain synaptosomal preparation, GAD67 is cleaved to its truncated form by an endogenous protease which is inhibited by specific calpain inhibitors. In mu-calpain knockout mice, the level of tGAD in the brain is greatly reduced compared with the wild type. When mu-calpain gene is silenced by siRNA, the level of tGAD is also markedly reduced compared to the control group. Mu-calpain is activated by neuronal stimulation and Ca2+-influx. Calpastatin inhibits GAD67 processing, calpains inhibit the GAD cleavage in vivo, mutational analysis, overview
proteolytic modification
-
conversion of full-length GAD65 to truncated GAD65 is not the result of random post-mortem degradation, but that it is an intracellular process that is highly regulated. The cleavage is mediated by calpain, a Ca2+-dependent cysteine protease
lipoprotein
-
palmitoylation of cysteines 30 and 45 is critical for post-Golgi trafficking of GAD65 to presynaptic sites and for its relative dendritic exclusion, leading to the presynaptic clustering of GAD65
phosphoprotein
-
protein kinase A is responsible for phosphorylation and inhibition of GAD67 activity, while calcineurin is the phosphatase responsible for dephosphorylation and activation of GAD67
proteolytic modification
-
the purified recombinant GAD67 is cleaved by mu-calpain at specific sites in Ca2+-dependent manner. In brain synaptosomal preparation, GAD67 is cleaved to its truncated form by an endogenous protease which is inhibited by specific calpain inhibitors. In mu-calpain knockout mice, the level of tGAD in the brain is greatly reduced compared with the wild type. When mu-calpain gene is silenced by siRNA, the level of tGAD is also markedly reduced compared to the control group. Mu-calpain is activated by neuronal stimulation and Ca2+-influx. Calpastatin inhibits GAD67 processing, overview
proteolytic modification
-
conversion of full-length GAD65 to truncated GAD65 is not the result of random post-mortem degradation, but that it is an intracellular process that is highly regulated. The cleavage is mediated by calpain, a Ca2+-dependent cysteine protease
lipoprotein
Q05329, Q99259
palmitoylation of cysteines 30 and 45 is critical for post-Golgi trafficking of GAD65 to presynaptic sites and for its relative dendritic exclusion, leading to the presynaptic clustering of GAD65
additional information
-
the enzyme undergoes posttranslational processing
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
sitting drop vapor diffusion method, using 100 mM sodium acetate pH 5.5, 720 mM sodium formate, 9% (w/v) PEG 8000, and 9% (w/v) PEG 1000
Q42521
isoform GadB, native and reduced, vapour diffusion method
-
isozyme GADalpha in complex with L-glutarate
-
N-terminally truncated mutants of both isoform GAD65 and GAD67. GAD67 shows a thethered loop covering the active site, providing a catalytic environment that sustains 4-aminobutanoate production. In isoform GAD65, the same catalytic loop is inherently mobile promoting a side reaction that results in cofactor release and enzyme autoinactivation
-
UV/Vis spectra show a strong peak for holo-enzyme at 308 nm and a weak peak at 336 nm. Apo-enzyme has a 20% increase in fluorescence emission at 308 nm. Holo-enzyme shows a greater beta-sheet content than apo-enzyme, but both have a similar alpha-helix content
-
pH STABILITY
pH STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
3.5
6
B1B389, -
purified recombinant enzyme, the enzyme is stable within a pH range of pH 4.5 to pH 5.0, but is unstable below pH 4.0 and above pH 5.5
3.5
-
Q0GE18
purified enzyme, loss of about 35% activity at 40C after 5 h
4
-
-
24 h, 8C, 60% loss of activity
4
-
Q0GE18
purified enzyme, 40C, loss of 3% activity after 1 h, and of 10% activity after 5 h; purified enzyme, maximally stable at pH 4.0
4.5
8
-
-
5
7
-
24 h, 8C, stable
5.5
-
Q0GE18
purified enzyme, loss of about 40% activity at 40C after 5 h
7
-
-
25C, 2 h, stable
7
-
Q42521
Gad1 is not completely inactive at physiological pH and its residual activity is essential for normal plant development
7
-
-
the GAD activity determined at pH 7.0 in the absence of Ca2+/calmodulin is about 70% of the maximal activity at 5.6
8
-
-
24 h, 8C, 90% loss of activity
10
-
Q9AR41
beyond pH range 5.0-9.0 a sharp decline in enzyme stability is observed, and negligible activity is detected at pH above 10
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0
50
-
1 h, stable in this range
20
40
B1B389, -
purified recombinant enzyme, stable
25
-
-
pH 7.0, 2 h, stable
37
-
-
10 min, little loss of activity
37
-
-
pH 7.0, 1 h, 35% loss of activity
37
-
-
half-life of the recombinant enzyme is 1.27-2.35 h, unaffected by autoantibodies against the enzyme
40
-
-
stable up to
40
-
Q0GE18
purified enzyme, pH 4.0, loss of 10% activity after 5 h, stable below
45
-
-
45 min, 78% loss of activity
50
-
-
50% loss of activity after 24 min
50
-
-
pH 7.0, 30 min, 90% loss of activity
50
-
-
fairly unstable above
50
-
Q0GE18
purified enzyme, pH 4.0, loss of 3% activity after 1 h
51
-
-
transition temperature of wild-type enzyme
55
-
-
transition temperature of mutant enzyme K276H
60
70
Q9AR41
the enzyme is significantly inactivated when the temperature is increased to 60C, with 36 and 49% of the original activity being lost after 30 and 60 min of incubation respectively, and is completely inactivated at 70C
60
-
-
10 min, over 50% loss of activity
60
-
Q0GE18
purified enzyme, pH 4.0, loss of about 15% activity after 5 h
62
-
-
transition temperature of mutant enzyme K276A
70
-
-
1 h, 85% loss of activity
80
-
-
10 min, complete inactivation
80
-
Q0GE18
purified enzyme, pH 4.0, loss of about 50% activity after 5 h
85
-
-
purified recombinant enzyme, stable
95
-
-
purified recombinant enzyme, half-life is 3 h
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
by entrapping Escherichia coli glutamate decarboxylase into sodium alginate and carrageenan gel beads, the activity of immobilized GAD remains 85% during the initial five batches and the activity still remains 50% at the tenth batch
-
limited proteolysis by trypsin shows that the mutant enzyme is more resistant to proteolytic degradation than the wild-type enzyme
-
stability is optimal over 3 months, in lyophilized form at 20C
-
the recombinant human enzyme injected into LEW.1A rats shows a half-life of 2.77 h
-
using RNA polymerase sigma factor (RpoS) or glutathione transferase as fusion expression partners, the solubility of the enzyme significantly increases.
-
freezing-thawing leads to the partial increase of activity in the conidial homogenate
-
ATP and phosphate together with chlorides stabilize renal GAD
-
inactivation by repeated freezing and thawing
-
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-20C, stable for several months without loss of activity
-
-20C, enzyme concentration of at least 3 mg/ml, under argon, in 100 mM potassium phosphate buffer containing 2 mM 2-aminoethylisothiouronium bromide and 0.4 mM pyridoxal 5'-phosphate
-
-80C, 3 months. rGAD67/65 is stable
-
0C, slight decrease in activity after 2 days
-
-20C, stable for up to 1 month
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
Mono-Q column chromatography, hydroxylapatite column chromatography, and gel filtration
-
recombinant isoenzymes
-
CaM agarose column chromatography and Superdex 200 gel filtration
Q42521
DEAE-Sepharose column chromatography
P69910
in polyethylene glycol (PEG) and sodium sulfate aqueous two-phase system. The optimum system obtained for GAD purification is composed of PEG 4000, tie line length of 63.5%, a volume ratio of 2.31, a loading sample concentration of 0.4 g/ml, which produces a GAD recovery of 90% with the purification fold of 73. The purification fold declines from 71.73 to 23.27 with the addition of 1 mM NaCl
-
mutant enzymes K276A and K276H
-
centricon-100 gel filtration
-
glutathione Sepharose 4B column chromatography
-, Q7XJB3
amylose resin column chromatography, glutathione Sepharose 4B resin column chromatography; glutathione sepharose 4B resin column chromatography and amylose resin column chromatography; recombinant tagged enzyme from Escherichia coli strain DH5alpha
-
isoform GAD65 and GAD67 expressed in Escherichia coli as fusion protein with glutathione-S-transferase and 6*His-tagged isoforms GAD65 and GAD67 expressed in Saccharomyces cerevisiae
-
large-scale purification of GAD65 and GAD67
-
partial
-
recombinant His-tagged enzyme from Escherichia coli strain Rosetta-gami B (DE3) by nickel affinity chromatography
A9ZM78
recombinant enzyme 27fold from Escherichia coli strain DH5alpha by ammoniumn sulfate fractionation, hydrophobic interaction and anion exchange chromatography
B1B389, -
native enzyme 550fold from brain by ammonium sulfate fractionation, hydrophobic interaction chromatography inpresence of benzamidine, ultrafiltration, anion exchange chromatography, and gel filtration
-
ammonium sulfate fractionation, DEAE Sepharose column chromatography, and Superdex 200 gel filtration
Q9AR41
ammonium sulfate precipitation, DEAE-Sepharose column chromatography, and Superdex 200 gel filtration
-
from rice germ
-
Ni-NTA column chromatography
A0EJ89, -
recombinant enzyme by ammonium sulfate fractionation, hydrophobic interaction chromatography, and dialysis
-
native enzyme 22fold to homogeneity by ammonium sulfate fractionation, precipitation in N-methylpiperazine, anion exchange and hydrophobic interaction chromatography, and gel filtration
Q0GE18
3 enzyme form: alpha, beta and gamma
-
His binding resin column chromatography
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
expression in Escherichia coli
-
expressed in Escherichia coli BL21(DE3) cells
Q42521
gene GAD1, DNA and amino acid sequence determination and analysis, genotyping; gene GAD2, DNA and amino acid sequence determination and analysis, genotyping
-, Q4PRC2
expression as maltose binding protein-fusion protein
-
gene DjGAD, DNA and amino acid sequence determination and analysis
-
expressed in Escherichia coli BL21(DE3) cells
-
truncated enzyme, recloned into the Escherichia coli expression vector pET11a, the N-terminal 77-84 amino acid residues encoded by the cloned gene have been deleted
-
expressed in Escherichia coli JM109 cells
-, Q7XJB3
6*His-tagged isoforms GAD65 and GAD67 expressed in Saccharomyces cerevisiae
-
a hybrid cDNA is created by fusing a cDNA for amino acids 1-101 of GAD67 to a human cDNA for amino acids 96-585 of GAD65. The recombinant rGAD67/65 protein is expressed in yeast and has equivalent immunoreactivity to mammalian brain GAD with diabetes sera
-
creation of a hybrid form of GAD consisting of amino acids 1-101 of the human GAD67 protein fused to amino acids 96-585 of the human GAD65 protein, and modification of this to include a C-terminal hexa-His tag sequence. The hybrid GAD67/65-H6 is expressed in two yeast hosts: constitutively under the control of the plasmid oxidase promoter PGK1 in Saccharomyces cerevisiae, and inducibly under the control of the chromosomal alcohol oxidase promoter AOX1 in Pichia pastoris. The hybrid GAD67/65 is isolated at high specific activity and moderate yield, and the addition of the His6 tag sequence of the choice of the yeast strain does not appreciably affect enzyme activity, percentage recovery of GAD, protein purification or utility in diagnosis of diabetes in terms of specificity and sensitivity to the various sera
-
expressed in Escherichia coli; expressed in Escherichia coli DH5alpha cells; gene gadB, expression in Escherichia coli strain DH5alpha using plasmids pMAL-c2X and the pGEX-3X and fusion to the maltose binding protein or GST, cytoplasmic targeting, overview
-
expression as glutathione S-transferase-fusion protein
-
expression in Sacchaormyces cerevisiae, His-tag
-
Expression of aggregation-prone deletion mutant protein (amino acids 448-585) using RNA polymerase sigma factor (RpoS) or glutathione S-transferase as fusion partners in Escherichia coli strain BL21 (DE3).
-
expression of GAD65
-
expression of labeled GAD65 in CHO cells
-
expression of the full-length and truncated mutant enzymes, expression analysis
-
gene GAD1, genomic organization, the gene located within chromosome 2q31 encodes the isozyme GAD67
-
gene GAD65, recombinant expression of full-length human GAD65 in Chlamydomonas reinhardtii strain 137c chloroplast genome under the control of the Chlamydomonas reinhardtii chloroplast rbcL promoter and 5'- and 3'-UTRs by particle bombardment
-
genotyping and expression analysis of isozyme GAD1 and GAD2 genes in individuals from Ireland and North Ireland, detailed overview
-
GST-GAD fusion protein expressed in Escherichia coli
-
recombinant expression of isozyme GAD65 using the Spodoptera frugiperda transfection method
-
expressed in Corynebacterium glutamicum strain ATCC 13032
-
expressed in Escherichia coli BL21(DE3) cells
-
expression in Bacillus subtilis
-
gene gadB, DNA and amin acid sequence determination and analysis, expression of the His-tagged enzyme in Escherichia coli strains Rosetta-gami B (DE3) ad JM109
A9ZM78
gene gadB, DNA and amin acid sequence determination and analysis, expression in Escherichia coli strain DH5alpha
B1B389, -
expressed in Lactobacillus sakei strain B2-16
-
expression of the full-length and truncated mutant enzymes, expression analysis
-
GAD67 gene fragments from a TT2 cell genomic library, overexpression of the coding sequence of the EGFP-poly(A) gene in TT2 ES cells
-
gene GAD67, expression analysis
-
genes GAd65 and GAD67, expression analysis in brain tissues
-
expression in Escherichia coli
-
expression in Escherichia coli
-
expressed in Escherichia coli BL21-codonPlus-(DE3)-RIL cells
A0EJ89, -
recombinant expression and sequence comparisons
-
expression of deletion mutant (rGAD65)C45A/DELTA1-38 and (rGAD65)DELTA1-101, expression in COS-7 cells
-
expression of the full-length and truncated mutant enzymes, expression analysis
-
GAD65 and GAD67 expression analysis in embryo and adult hippocampi
-
gene GAD67, cloning of four GAD67 transcripts, GAD67-C1, -C2, -C3, and -C4, produced by alternative splicing and polyadenlyation and translating a GAD protein with truncated pyridoxal 5'-phosphate binding domain, which leads to a lack of glutamate decarboxylase activity, expression in HEK-293 cells
-
genes GAd65 and GAD67, expression analysis in brain tissues
-
tissue expression pattern of GAD67, overview
-
gene gadB, DNA and amino acid sequence determination and analysis
Q0GE18
expressed in Escherichia coli BL21(DE3) cells
-
EXPRESSION
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
glutamic acid decarboxylase67 mRNA expression is decreased in multiple brain areas of patients with schizophrenia and mood disorders
Q99259
when ginseng seedlings are exposed to chilling stresses at 4C, the GAD mRNA level is slightly induced at 1 h and 4 h, with 2.81 and 2.74fold higher than the control plants, the expression level then rapidly peaks at 8 h with 5.94fold induction. Heat stress (37C) causes a rapid induction of GAD to 3.05fold at 1 h post-treatment. Anoxia stress triggers the response of GAD at early stage. A significant induction (6.94fold) of gene is observed at 1 h post treatment.
-
GAD expression is induced in response to the production of compression wood and GAD increases during day 14 and 82 after germination in the hypocotyl
A0EJ89, -
exposure of cell cultures to intermittent hypoxia decreases GAD67 activity. intermittent hypoxia-evoked decrease in GAD67 activity is caused by increased cAMP - protein kinase A - dependent phosphorylation of GAD67, but not as a result of changes in either GAD67 mRNA or protein expression
-
GAD65 gene expression is dynamically regulated at multiple levels during post-natal testis maturation, GAD65 protein is presented in Leydig cells of day 1 testis, primary spermatocytes and spermatids of postnatal of day 90 testis
-
in the herpes simplex virus-GAD group, GAD67 mRNA and protein levels are significantly increased in the L6-S1 dorsal root ganglia
-
subchronic L-DOPA administration (6 mg/kg) is paralleled by a significant increase in mRNA levels of the two isoforms of glutamic acid decarboxylase (GAD67 and GAD65), 1 mg/kg 2-methyl-6-(phenylethynyl)-pyridine completely reverses the effects of L-DOPA on GAD67 and GAD65 and reduces the increases in mRNA levels
-
GAD1 gene is upregulated and GAD activity is increased in the leaves and roots after treatment with 0.1 mM ABA, 0.1 mM methyl jasmonate, 0.8% (w/v) NaCl, 20% (w/v) polyethylene glycol, or cold stress
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
H465A
P69910
the mutant is active at pH well above 5.7 and shows 78% of wild type specific activity in 0.2 M pyridine/HCl buffer, pH 4.6, at 37C in the presence of 0.1 mM pyridoxal 5'-phosphate
K276A
-
no decarboxylation of L-Glu. Transition temperature is 11C higher than that of the wild-type enzyme. Limited proteolysis by trypsin shows that the mutant enzyme is more resistant to proteolytic degradation than the wild-type enzyme. Mutant enzyme contains very little pyridoxal 5'-phosphate
C30A
Q05329, Q99259
mutation of Cys30 to Ala abolishes the presynaptic clustering of GAD65 in primary hippocampal neurons
T91A
-
abolishes phosphorylation by protein kinase A and subsequent inhibition of enzyme activity
T91D
-
mimics the inhibiting effect of enzyme phosphorylation
DELTAC9
-
9 amino acid C-terminal deletion mutant, no formation of complexes larger than 340 kDa, no activation by Ca2+/calmodulin. The ability to bind calmodulin in the presence of Ca2+ is retained, and mutant may be purified by calmodulin affinity chroamtography. 12% of wild-type activity at pH 5.8
K496A/K497A
Q42521
the mutant displays a substantial loss of enzymatic activity, at the pH optimum, the activity of the double mutant is reduced about 3fold
additional information
-, Q4PRC2
determination of single nucleotide polymorphisms in gene GAD1, i.e. A1005G and A399C, genotypes and allele frequencies, overview; determination of single nucleotide polymorphism T1095C in gene GAD2, genotype and allele frequency, overview
K276H
-
no decarboxylation of L-Glu. Transition temperature is 4C higher than that of the wild-type enzyme. Mutant enzyme contains no pyridoxal 5'-phosphate
additional information
P69910
the mutant GadBDELTAHT (His465 of GadB is deleted together with the last residue in the polypeptide chain, Thr466) is active at pH well above 5.7 and shows 52% of wild type specific activity in 0.2 M pyridine/HCl buffer, pH 4.6, at 37C in the presence of 0.1 mM pyridoxal 5'-phosphate
C45A
Q05329, Q99259
mutation of Cys30 to Ala abolishes the presynaptic clustering of GAD65 in primary hippocampal neurons
additional information
-
creation of a hybrid form of GAD consisting of amino acids 1-101 of the human GAD67 protein fused to amino acids 96-585 of the human GAD65 protein, and modification of this to include a C-terminal hexa-His tag sequence. The hybrid GAD67/65-H6 is expressed in two yeast hosts: consitutively under the control of the plasmid oxidase promoter PGK1 in Saccharomyces cerevisiae, and inducibly under the control of the chromosomal alcohol oxidase promoter AOX1 in Pichia pastoris. The hybrid GAD67/65 is isolated at high specific activity and moderate yield, and the addition of the His6 tag sequence of the choice of the yeast strain does not appreciably affect enzyme activity, percentage recovery of GAD, protein purification or utility in diagnosis of diabetes in terms of specificity and sensitivity to the various sera
additional information
-
a hybrid cDNA is created by fusing a cDNA for amino acids 1-101 of GAD67 to a human cDNA for amino acids 96-585 of GAD65. The recombinant rGAD67/65 protein is expressed in yeast and has equivalent immunoreactivity to mammalian brain GAD with diabetes sera. rGAD67/65 has enzymatic properties similar to that of the mixed isoforms of GAD preparations from mammalian brain
additional information
-
expression and characterization of naturally occurring shorter forms of enzyme. Isoform GAD67 with N-terminal deletion of 70 or 90 amino acids has about 20% of wild-type activity
additional information
-
crystallization data of N-terminally truncated isoform GAD67, expressing amino acids 90-594, catalytically active, and of N-terminally truncated isoform GAD65 expressing amino acids 84-585
additional information
-
construction of a truncated enzyme version
additional information
-
detection of a naturally occuring mutant with nine single nucleotide polymorphisms spanning the promoter region of the GAD1 gene to the 3'-UTR
additional information
-
construction of transgenic Chlamydomonas reinhardtii expressing the human enzyme in chloroplasts, expression analysis and immunohistochemic protein detection, overview
T91E
-
mimics the inhibiting effect of enzyme phosphorylation
additional information
-
isoform GAD65 knock-out mice show upregulated level of vesicular gamma-aminobutanoate transporter, and no change in the synaptic vesicles-associated isoform GAD67. In mutant mice, synaptic vesicles transport cytosolic gamma-aminobutanoate much more efficiently than wild-type
additional information
-
construction of cerebellum-selective GAD67-knockout mice, selective GAD67 deletion in the cerebellum iss achieved using a Cre-loxP strategy. GABA level is reduced to 16-44% in the cerebellum but not in the cerebrum, inhibitory synaptic transmission to Purkinje cells is seriously impaired, however, the morphology of Purkinje cells and the density of synaptic terminals in the cerebellar cortex appears unaffected, phenotype, overview
additional information
-
targeted ablation of the GAD65 gene in Gad65-/- mice results in a pronounced context-independent, intramodal generalization of auditory fear memory during long-term/24 h or 14 d but not short-term/30 min memory retrieval, phenotype analysis, overview
additional information
-
construction of cells overexpressing the GFP-tagged enzyme in membranes of cell somata, dendrites, axons and synaptic terminals of dentate neurons, subcellular localization, correlation to the amount of voltage-gated potassium channels Kv3.1b and Kv3.3, overview
additional information
-
construction of GFP-tagged GAD67 overexpressing mutant mice
additional information
Q9AR41
mutant lacking 31 amino acids at C-terminal extension shows 40fold higher activity than wild-type at physiological pH value. Rice plants overexpressing the mutant enzyme have aberrant phenotypes such as dwarfism, etiolated leaves, and sterility
DELTAN18
-
18 amino acid N-terminal deletion mutant, activation by Ca2+/calmodulin is reduced by about 50%. 40% of wild-type activity at pH 5.8
additional information
-
development of a hyperthermostable enzyme for industrial applications, overview
additional information
-
construction of a truncated enzyme version
additional information
-
the recombinant human enzyme injected into LEW.1A rats shows a half-life of 2.77 h
additional information
-
construction of a C-terminal 44-kDa truncated GAD, i.e. GAD44. GAD25 corresponds to the putative regulatory domain of the full-length protein, GAD44 contains the cofactor-binding site and enzymatic activity for synthesis of gamma-butyric acid
additional information
Rattus norvegicus LEW-1A
-
the recombinant human enzyme injected into LEW.1A rats shows a half-life of 2.77 h
-
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
medicine
-
injection of gamma-aminobutanoate agonists baclofen and muscimol increases luteinising hormone in serum after 6 h. Intraperitoneal treatment with gamma-aminobutanaote A agonist muscimol decreases mRNA of isoform GAD65 approximately 10fold, gamma-aminobutanaote transaminase approximately 15fold and tyrosine hydroxylase approximately 3fold in telencephalon. Intraperitoneal treatment with gamma-aminobutanaote B agonist baclofen reduces mRNA levels of isoform GAD67 approximately 2fold and gamma-aminobutanaote transaminase approximately 2fold in hypothalamus
medicine
-
incubation of rat hippocampal slices with the potassium channel antagonis tetraethyl ammonium results in widespread excitotoxic death of pyramidal and granule cell neurons. Treatment with bacterial enzyme significantly reduces excitotoxicity induced by tetraethyl ammonium without showing neurotoxicity. Targeting of enzyme to the interior of synaptic vesicles may enhance its potency as a neuroprotectant
analysis
-
the diabetes autoantibody standardization program, DASP, aims to improve and standardize measurement of autoantibodies, e.g. glutamic acid decarboxylase autoantibodies and islet antigen-2, against associated with type 1 diabetes, overview
diagnostics
-
the enzyme is useful in diagnostics of type I diabetes mellitus, detection of autoantibodies by RSR-ELISA with Ca2+-free plasma samples, method development, overview
diagnostics
-
GAD65 is a predictive marker for the insulin depletion in diabetes mellitus
diagnostics
-
GAD-involving latent autoimmune type 1 diabetes can be distinguished from type 2 diabetes by detection of anti-GAD antibodies, oerview
diagnostics
-
the enzyme is a potential important marker for the prediction and diagnosis of type 1 diabetes
diagnostics
-
type 1 diabetes, T1D, patients and Stiff Person Syndrome, SPS, patients show a specific lack of anti-Ids to disease-associated GAD65Ab epitopes, autoantibodies to glutamate decarboxylase 65 are a major characteristic for type 1 diabetes and and Stiff PersonSyndrome patients
medicine
-
the autoantibody profile in a variety of patients with diabetes and thyroid autoimmune diseases is probed by a set of GAD65/67 variants: GAD65, GAD65/67 hybrids spanning residues 1-95, 96-444 and 445-585, deltaGAD65, a truncated GAD65 spanning residues 69-585 and GAD67. DeltaGAD65 and GAD65 detect 137 and 125 positive patients, respectively. The hybrids react with 113 sera and in 3 cases disclosed cryptic epitopes. Eighteen patients react with GAD67, indicating GAD65-GAD67 cross-reactivity
medicine
-
positivity for either GAD65 or ICA512/IA-2 Ab is a highly sensitive marker of type 1 diabetes in the pediatric age group
medicine
-
mutation screen of isoform GAD67 in patients diagnosed with major unipolar depression shows a significant within-gene linkage disequilibrium. A common genetic variation within the GAD67 gene does not play a major role in predisposition to unipolar depression
medicine
-
enzyme plus murine IL-4 expressed in tobacco and fed to nonobese diabetic mice protects from diabetes. Feeding enhances levels of IgG1 anti-enzyme antibodies, increases splenocyte IL-4/IFN-gamma cytokine responses and produces protective regulatory T-cells
pharmacology
-
the enzyme is a potential important marker for the prediction and diagnosis of type 1 diabetes, and for the development of antigen-specific therapies for the treatment of type 1 diabetes
nutrition
-
use of Bacillus subtilis strain expressing L-glutamate decarboxylase from Lactobacillus brevis for preparation of Korean fermented soybean product Chungkukjang results in significantly higher levels of gamma-aminobutanoate in products
food industry
-
the specific inhibition of GAD activity or a reduction in the levels of free glutamate may prevent the growth of otherwise resistant GAD+ bacteria in foods where low pH and/or nisin is used as a preservative
food industry
-
the specific inhibition of GAD activity or a reduction in the levels of free glutamate may prevent the growth of otherwise resistant GAD+ bacteria in foods where low pH and/or nisin is used as a preservative
-
food industry
-
the specific inhibition of GAD activity or a reduction in the levels of free glutamate may prevent the growth of otherwise resistant GAD+ bacteria in foods where low pH and/or nisin is used as a preservative
food industry
-
the specific inhibition of GAD activity or a reduction in the levels of free glutamate may prevent the growth of otherwise resistant GAD+ bacteria in foods where low pH and/or nisin is used as a preservative
-
medicine
-
hamsters treated with low-dose cocaine throughout adolescence show significant differences to control in enzyme immunoreaction in anterior hypothalamus, medial and central amygdaloid nuclei, lateral septum
medicine
-
glutamic acid specific T-cells play a key role in type I diabetes. Isolation of several populations of glutamic acid decarboxylase peptide-specific T-cells from diabetes-prone non-obese and diabetes-resistant mice. The repertoire of T cells specific for these peptides is biased toward Tr cells that inhibit diabetes rather than toward pathogenic T cells that induce diabetes
synthesis
-
expression of enzyme in Bifidobacterium longum in medium containing monosodium glutamate, significant increase in production of gamma-aminobutyric acid
analysis
-
most important application of glutamate decarboxylase antibodies is to identify those neurons and neuronal projections that use 4-aminobutanoate as their neurotransmitter by immunocytochemical visualization
medicine
-
eight hours following kainate- or pilocarpine-induced seizure of piriform cortex, severe neuronal damage is observed accompanied by significant decreases in enzyme protein. In layer II of the central pirifiorm cortex, significant increase in isoforms GAD65 and GAD67 mRNA is determined
medicine
-
herpes simplex virus -based GAD gene transfer to bladder afferent pathways represents an approach for treatment of neurogenic detrusor overactivity