6.3.2.2: glutamate-cysteine ligase
This is an abbreviated version!
For detailed information about glutamate-cysteine ligase, go to the full flat file.
Word Map on EC 6.3.2.2
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6.3.2.2
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ganglion
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retinal
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nerve
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heme
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plexiform
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fiber
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sulfoximine
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dismutase
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coherence
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tomography
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buthionine
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s-transferase
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oxygenase-1
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macular
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erythroid
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quinone
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neuroprotective
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2-related
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amacrine
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cytoprotective
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gssg
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nadph:quinone
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glaucoma
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nf-e2-related
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acuity
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transpeptidase
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sd-oct
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peripapillary
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intravitreal
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nrf2-mediated
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nrf2-dependent
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dentate
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spectral-domain
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nrf2-are
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factor-erythroid
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subgranular
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glutathione-related
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gsh-dependent
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phytochelatins
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l-buthionine-s,r-sulfoximine
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tert-butylhydroquinone
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oxidoreductase-1
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ech-associated
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kelch-like
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nrf2-regulated
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fovea
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biotechnology
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medicine
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perimetry
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synthesis
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gsh-depleting
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agriculture
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drug development
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etdrs
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pharmacology
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spectralis
- 6.3.2.2
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ganglion
- retinal
- nerve
- heme
-
plexiform
- fiber
- sulfoximine
- dismutase
-
coherence
-
tomography
-
buthionine
- s-transferase
- oxygenase-1
-
macular
-
erythroid
- quinone
-
neuroprotective
-
2-related
-
amacrine
-
cytoprotective
- gssg
-
nadph:quinone
- glaucoma
-
nf-e2-related
-
acuity
- transpeptidase
-
sd-oct
-
peripapillary
-
intravitreal
-
nrf2-mediated
-
nrf2-dependent
-
dentate
-
spectral-domain
-
nrf2-are
-
factor-erythroid
-
subgranular
-
glutathione-related
-
gsh-dependent
- phytochelatins
-
l-buthionine-s,r-sulfoximine
- tert-butylhydroquinone
-
oxidoreductase-1
-
ech-associated
-
kelch-like
-
nrf2-regulated
-
fovea
- biotechnology
- medicine
-
perimetry
- synthesis
-
gsh-depleting
- agriculture
- drug development
-
etdrs
- pharmacology
-
spectralis
Reaction
Synonyms
Ace-GCL, Asuc_1947, AtGCL, bifunctional glutathione synthetase, bifunctional GSH synthetase, bifunctional L-glutathione synthetase, gamma -GCS, gamma-ECL, Gamma-ECS, gamma-GC, gamma-GCS, gamma-GCS-GS, gamma-glutamate-cysteine ligase-glutathione synthetase, gamma-glutamate-cysteine ligase/glutathione synthetase, gamma-glutaminylcysteine synthetase, gamma-glutamycysteine synthetase, gamma-glutamyl-cysteine ligase, gamma-Glutamyl-L-cysteine synthetase, gamma-glutamylcysteine ligase, gamma-glutamylcysteine synthase, gamma-Glutamylcysteine synthetase, gamma-glutamylcysteine synthetase-glutathione synthetase, gamma-Glutamylcysteinyl-synthetase, gammaGCS, GCL, GCLC, Gclc-X2, GCLM, GCS, GCSGS, ghF, GLCL, GLCLC, GLCLR, glutamate cysteine ligase, glutamate cysteine ligase gene, glutamate-cysteine ligase, glutamate-cysteine-ligase, glutamate–cysteine ligase, glutathione biosynthesis bifunctional protein GshAB, GSH1, GshA, gshAB, GshF, GshFAp, GshFAs, GSHI, I79_022778, L-glutamate L-cysteine ligase, More, PAD2, PhGshA II, PSHAa0937, StGCL-GS, Synthetase, gamma-glutamylcysteine
ECTree
6.3.2.2 glutamate-cysteine ligaseAdvanced search results
results (
results (Activating Compound
Activating Compound on EC 6.3.2.2 - glutamate-cysteine ligase
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ACTIVATING COMPOUND 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
IMAGE
1-(4-amino-2-methyl-5-pyridimidyl)-methyl-3-(2-chloroethyl)-3-nitrosurea
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induces expression of heavy subunit
2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2-methoxy-1-methylethyl)-acetamide
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i.e. metolachlor, a herbicide that decreases the plant growth and and biomass, induction of enzyme expression, enhanced enzyme activity leads to enhanced detoxification activity
2-chloro-N-(ethoxymethyl)-N-(2-ethyl-6-methylphenyl)-acetamide
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i.e. acetochlor, a herbicide that decreases the plant growth and and biomass, induction of enzyme expression, enhanced enzyme activity leads to enhanced detoxification activity
activator protein 1
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i.e. AP-1, is required for basal expression of the enzyme
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apigenin
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nearly 2fold induction of the heavy subunit gene promotor and heavy subunit expression
cadmium aerosols
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2.4 mg Cd/m3, enhance in the lung the expression of the enzyme's heavy, catalytic subunit gamma-GCS-HS by 4.5fold after 15 min, 8fold after 6 h, increase in enzyme activity and GSH production rate
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cafestol
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coffee component, induction of the enzyme in vivo, especially in the liver up to 2.4fold, increase in expression of both enzyme subunits
caffeic acid
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treatment of the cells with 100 and 500 microg/ml of caffeic acid increases gamma-GCS activities by 1.4- and 1.8fold compared to the control group, respectively. At the same doses of caffeic acid, the treated cells show increased levels of glutathione by 1.7- and 2.7fold compared to the control, respectively
carbon tetrachloride
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a single dose of 1589 mg/kg body weight of carbon tetrachloride causes changes in CGL activity and glutathione content in multiple organs of deer mice. Hepatic GCL activity and GSH content are depleted substantially, renal GCL activity increases. Blood, brain and heart GCL activities increase, whereas GSH contents decrease significantly
ethanol
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feeding in vivo increases the enzyme expression, treatment of hepatocytes induces the expression of only the heavy enzyme subunit
hydrocortisone
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treatment of hepatocytes induces the expression of only the heavy enzyme subunit
Insulin
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treatment of hepatocytes induces the expression of only the heavy enzyme subunit
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kaempferol
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2fold induction of the heavy subunit gene promotor and heavy subunit expression
kahweol
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coffee component, induction of the enzyme in vivo, especially in the liver up to 2.4fold, increase in expression of both enzyme subunits
mcCDC34
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an ubiquitine conjugated protein, induces gamma-glutamylcysteine synthetase expression only in glutathione synthetase-dficient mutants, not in the wild-type
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nitric oxide
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induces expression of heavy and light subunit via direct exposure or interleukin-1 induced
onion extract
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containing flavonoids, which increase the expression of both subunits of the enzyme in COS-1 cells
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oxidative stress
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activation of GCL occurrs within min of treatment and without any change in GCL protein levels, and coincides with an increase in the proportion of GCL catalytic subunit in the holoenzyme form. Likewise, GCL modifier subunit shifts from the monomeric form to holoenzyme and higher molecular weight species. Neither GCL activation, nor the formation of holoenzyme, requires a covalent intermolecular disulfide bridge between GCL catalytic subunit and GCL modifier subunit. In immunoprecipitation studies, a neutralizing epitope associated with enzymatic activity is protected following cellular oxidative stress. Thus, the N-terminal portion of GCL catalytic subunit may undergo a change that stabilizes the GCL holoenzyme. Results suggest a dynamic equilibrium between low- and high-activity forms of GCL, which is altered by transient oxidative stress
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quercetin
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3fold induction of the heavy subunit gene promotor and heavy subunit expression, best at 0.05 mM, induction even of a distal part of the promotor sequence containing only 2 antioxidant-response/electrophile-response elements, i.e. ARE/EpRE
2,3-dimethoxy-1,4-naphthoquinone
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induces expression of heavy and light subunit
2,3-dimethoxy-1,4-naphthoquinone
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induces expression of heavy and light subunit
4-hydroxy-2-nonenal
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i.e. 4-HNE, inductor of enzyme expression, signals through the JNK pathway, most effective at 0.02 mM, time-dependence is different for GCLC and GCLM, overview, also activates the transcription factor complex AP-1 which itself activates expression of both enzyme subunits
4-hydroxy-2-nonenal
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4-hydroxy-2-nonenal causes a rapid dose- and time-dependent increase in A549 cell GCL activity. Maximal activation of GCL occurs at 30 min in response to 50 microM 4-hydroxy-2-nonenal
AP-1
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transcription factor complex including Jun family members, drives expression of both enzyme subunit encoding genes, AP-1 complex is activated by 4-hydroxy-2-nonenal, enzyme induction can be blocked by membrane-permeable peptide-based JNK inhibitor JNKi, but not by inhibitors SB202190 or PD98059
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H2O2
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40-50% increase in intracellular concentration induces enzyme expression 2fold to upregulate GSH production, GSH is required for detoxification, increase is reversible or preventable by peroxide-eliminating substances
H2O2
induction of enzyme expression, increase in activity in V79 cells independent on transcription level
L-cysteine
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varying glutamic acid concentrations from 5 to 80 mM do not affect GCL activities markedly, whereas cysteine concentrations from 2.5 to 40 mM influence GCL activities substantially in a tissue-dependent manner, about 20 mM L-Cys is optimal in the different tissue, overview. After subacute exposure, low doses increases GCL activity and GSH content in liver by 48.3% and 54.4%, respectively. High doses reduce GCL activities significantly in liver and kidney to 31.2% and 43.0% of the control, respectively
L-cysteine
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varying glutamic acid concentrations from 5 to 80 mM do not affect GCL activities markedly, whereas cysteine concentrations from 2.5 to 40 mM influence GCL activities substantially in a tissue-dependent manner, about 20 mM L-Cys is optimal in the different tissue, overview. Low doses activate high doses inhibits the enzyme
L-cysteine
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varying glutamic acid concentrations from 5 to 80 mM do not affect GCL activities markedly, whereas cysteine concentrations from 2.5 to 40 mM influence GCL activities substantially in a tissue-dependent manner, about 20 mM L-Cys is optimal in the different tissue, overview. Low doses activate high doses inhibits the enzyme
pyrrolidine dithiocarbamate
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time-, dose-, and Cu2+-dependent induction and increase in expression levels of the 2 subunits of the enzyme in HepG2 cells, mechanism, can be partially blocked by N-acetylcysteine and by copper chelator bathocuproine disulfonic acid
tert-butylhydroquinone
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i.e. TBH, exerts a dose- and time-dependent increase in the mRNA level and promotor activity of the 2 genes encoding the enzyme subunits
additional information
In response to redox environment, AtGCL undergoes a reversible conformational change that modulates the enzymatic activity of the monomer
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additional information
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In response to redox environment, AtGCL undergoes a reversible conformational change that modulates the enzymatic activity of the monomer
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additional information
both GCLC gene expression and total GSH levels increase 4 and 1.5fold, respectively, in response to hyperthermal stress, overview
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additional information
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both GCLC gene expression and total GSH levels increase 4 and 1.5fold, respectively, in response to hyperthermal stress, overview
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additional information
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multiple cis- and trans-elements have up-regulating effect on expression of the heavy catalytic subunit and of the regulatory light subunit, ionization radiation induces expression of heavy subunit, overview, effect of miscellaneous treatments on enzyme mRNA expression, overview
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additional information
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no increase in gene promotor activity by myricetin and sugar conjugates of quercetin, quercetin-3-glucoside and quercetin-3-rhamnoglucoside
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additional information
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no induction of enzyme production in HepG2 cells by overexpression of human cytochrome 3A4
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additional information
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extracts of Ginkgo biloba induces GCL catalytic subunit, GCLC, in HepG2 and Hep1c1c7 cell lines
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additional information
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resveratrol and 4-hydroxy-2-nonenal both increases GSH and the mRNA contents of both the catalytic GCLC and modulatory GCLM subunit of GCL, both agents show synergictic effects when applied together, overview. The cis-element Nrf2/EpRE signalling is involved in resveratrol-mediated induction of GCL genes
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additional information
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subunit GCLM increases the Vmax and Kcat of subunit GCLC, and decreases the Km for glutamate and ATP
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additional information
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the enzyme is induced by 4-hydroxy-2-nonenal through the c-Jun N-terminal kinase pathway, the regulation involves SHP-1, the protein-tyrosine phosphatase SH" domain containing phosphatase-1 in HBE1 cells, mechanism, overview
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additional information
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under low glucose levels insulin induces an approximate 2fold increase in expression of gamma-glutamylcysteine ligase catalytic subunit GCLc mRNA and protein, which does not lead to increased GSH levels in the cell
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additional information
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ionization radiation induces expression of heavy subunit, effect of miscellaneous treatments on enzyme mRNA expression, overview
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additional information
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induction of Gclc by homocysteine, ARE4 plays a direct role in mediating the induction, Nrf2 signalling is critical in homocysteine-induced activation of ARE4, overview
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additional information
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subunit GCLM increases the Vmax and Kcat of subunit GCLC, and decreases the Km for glutamate and ATP
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additional information
GCL forms a homodimer under oxidizing conditions, and is activated more than threefold
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additional information
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GCL forms a homodimer under oxidizing conditions, and is activated more than threefold
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additional information
high activity in 100-300 mM Tris buffer
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additional information
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effect of miscellaneous treatments on enzyme mRNA expression, overview
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additional information
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two-thirds partial hepatectomy increases the enzyme expression
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additional information
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GCLC expression is 3fold up-regulated 1 h after induction of edematous pancreatitis
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additional information
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subunit GCLM increases the Vmax and Kcat of subunit GCLC, and decreases the Km for glutamate and ATP
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