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Literature summary for 6.3.2.2 extracted from

  • Griffith, O.W.; Mulcahy, R.T.
    The enzymes of glutathione synthesis: gamma-glutamylcysteine synthetase (1999), Adv. Enzymol. Relat. Areas Mol. Biol., 73, 209-267.
    View publication on PubMed

Activating Compound

Activating Compound Comment Organism Structure
H2O2 induction of enzyme expression, increase in activity in V79 cells independent on transcription level Homo sapiens
H2O2 induction of in enzyme expression and activity Saccharomyces cerevisiae

Application

Application Comment Organism
medicine enzyme inhibitor L-buthionine-S-sulfoximine is used to modulate GSH levels in cancer patients, overview Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
DNA sequence determination and analysis [Candida] boidinii
DNA sequence determination and analysis Escherichia coli
DNA sequence determination and analysis Arabidopsis thaliana
DNA sequence determination and analysis Leishmania tarentolae
DNA sequence determination and analysis, gene Gsc1, expression in and functional complementation of an enzyme-deficient mutant strain Schizosaccharomyces pombe
DNA sequence determination and analysis, gene GSH1 maps to chromosome X, expression in and functional complementation of an enzyme-deficient mutant strain, the yAP-1 responsive element in the promotor of gene GSH1 is involved in transcription of the gene in response to exposure to cadmium or hydrogen peroxide Saccharomyces cerevisiae
DNA sequence determination and analysis, heavy and light subunits, overexpression of catalytic subunit and holoenzyme in Escherichia coli BL21(DE3) Rattus norvegicus
DNA sequence determination and analysis, mapping to chromosome 6p12, heavy and light subunits, overexpression in Escherichia coli, individual or coexpression of the 2 subunits in COS cells, expression patterns, expression of several deletion mutants created fom the 5'-flanking region of the gene in human hepatoblastoma HepG2 cells, overexpression in human leukemia HL-60 cells Homo sapiens
DNA sequence determination and analysis, mapping to chromosome 6p12, heavy and light subunits, overexpression in Escherichia coli, individual or coexpression of the 2 subunits in COS cells, expression patterns, expression of several deletion mutants created fom the 5'-flanking region of the gene in humen hepatoblastoma HepG2 cells, overexpression in human leukemia HL-60 cells Homo sapiens
DNA sequence determination and analysis, mapping to chromosome 9, band D-E, heavy and light subunits Mus musculus
DNA sequence determination and analysis, overexpression in Escherichia coli Trypanosoma brucei

Protein Variants

Protein Variants Comment Organism
H150A site-directed mutagenesis, inactive mutant Rattus norvegicus
K38N site-directed mutagenesis, 50% reduced activity and 2 to 3fold increased Km for L-Glu compared to the wild-type Rattus norvegicus
K38Q site-directed mutagenesis, 50% reduced activity and 2 to 3fold increased Km for L-Glu compared to the wild-type Rattus norvegicus
K38R site-directed mutagenesis, slightly decreased activity Rattus norvegicus
additional information mutation of yAP-1 consensus sequence inhibits binding of yAP-1 protein, rendering the GSH1 promotor nonresponsive to exogenously expressed yAP-1 Saccharomyces cerevisiae
additional information mutational analysis of the 5'-flanking sequence of the heavy subunit, site-directed mutagenesis Homo sapiens

General Stability

General Stability Organism
enzyme is inactivated by freezing Sus scrofa
enzyme is inactivated by freezing Bos taurus
enzyme is inactivated by freezing Ovis aries
enzyme is inactivated by freezing Proteus mirabilis
enzyme is inactivated by freezing [Candida] boidinii
enzyme is inactivated by freezing Mus musculus
enzyme is inactivated by freezing Homo sapiens
enzyme is inactivated by freezing Rattus norvegicus
glycerol is required for enzyme stability during storage Homo sapiens
glycerol is required for enzyme stability during storage Rattus norvegicus
inactivated by freezing Mus musculus
L-glutamate stabilizes the enzyme during purification Rattus norvegicus
L-glutamate stabilizes the enzyme during purification, Homo sapiens
L-glutamate stabilizes the enzyme during purification, Rattus norvegicus
Mn2+ destabilizes the enzyme during purification Homo sapiens
Mn2+ destabilizes the enzyme during purification Rattus norvegicus

Inhibitors

Inhibitors Comment Organism Structure
4-methylene-L-glutamate weak, competitive Rattus norvegicus
5-Chloro-4-oxo-L-norvaline irreversible, binding is reduced by L-glutamate, increased by L-alpha-aminobutyrate, and is completely dependent on divalent cations Rattus norvegicus
buthionine sulfone
-
Rattus norvegicus
buthionine sulfoximine
-
Arabidopsis thaliana
buthionine sulfoximine
-
Ascaris suum
buthionine sulfoximine
-
[Candida] boidinii
buthionine sulfoximine
-
Leishmania tarentolae
buthionine sulfoximine
-
Nicotiana tabacum
buthionine sulfoximine
-
Saccharomyces cerevisiae
buthionine sulfoximine
-
Schizosaccharomyces pombe
Chloroacetone
-
Rattus norvegicus
cysteamine rapid inactivation, reversible by thiols Bos taurus
cysteamine rapid inactivation, reversible by thiols Homo sapiens
cysteamine rapid inactivation, reversible by thiols Mus musculus
cysteamine rapid inactivation, reversible by thiols Ovis aries
cysteamine rapid inactivation, reversible by thiols Rattus norvegicus
cysteamine rapid inactivation, reversible by thiols Sus scrofa
D-3-amino-1-chloro-2-pentanone
-
Rattus norvegicus
gamma-methylene-D-glutamate
-
Rattus norvegicus
GSH feedback inhibition Ascaris suum
GSH feedback inhibition Bos taurus
GSH feedback inhibition [Candida] boidinii
GSH feedback inhibition Escherichia coli
GSH feedback inhibition Homo sapiens
GSH feedback inhibition Mus musculus
GSH feedback inhibition Nicotiana tabacum
GSH feedback inhibition Ovis aries
GSH feedback inhibition, competitive to L-Glu Rattus norvegicus
GSH feedback inhibition Sus scrofa
GSH feedback inhibition Trypanosoma brucei
iodoacetamide
-
Rattus norvegicus
L-buthionine sulfone competitive, reversible Rattus norvegicus
L-buthionine-R-sulfoximine
-
Escherichia coli
L-buthionine-R-sulfoximine
-
Homo sapiens
L-buthionine-R-sulfoximine mechanism-based, competitive, reversible Rattus norvegicus
L-buthionine-S-sulfoximine strong inhibition Escherichia coli
L-buthionine-S-sulfoximine strong inhibition Homo sapiens
L-buthionine-S-sulfoximine mechanism-based, ATP-dependent, nearly irreversible inhibition in presence of Mg2+ and ATP, if ATP and Mg2+ are remove the activity is restored Rattus norvegicus
methionine sulfoximine
-
Mus musculus
methionine sulfoximine competitive and reversible Rattus norvegicus
additional information no inhibition by cysteamine or slowly at high concentration Escherichia coli
additional information no inhibition by alpha-ethyl-methionine sulfoximine Mus musculus
additional information inhibition mechanisms, no inhibition by L-homocysteine sulfonate Rattus norvegicus
NO
-
Mus musculus
ophthalmic acid
-
Rattus norvegicus
S-butyl-DL-homocysteine-SR-sulfoximine
-
Mus musculus
S-butyl-DL-homocysteine-SR-sulfoximine
-
Rattus norvegicus
S-nitroso-L-cysteine inactivation, prevented by pretreatment with ATP and L-SR-buthionine sulfoximine in absence of Mg2+ Rattus norvegicus
S-nitroso-L-cysteinylglycine inactivation, prevented by pretreatment with ATP and L-SR-buthionine sulfoximine in absence of Mg2+ Rattus norvegicus
S-sulfo-homocysteine
-
Rattus norvegicus
S-sulfo-L-cysteine
-
Rattus norvegicus
Trinitrobenzene sulfonate inactivates the enzyme Rattus norvegicus

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
additional information
-
additional information kinetics, kinetic mechanism Rattus norvegicus
0.09
-
L-cysteine strain B Escherichia coli
0.1
-
L-cysteine strain W Escherichia coli
0.1
-
ATP strain B Escherichia coli
0.1
-
L-cysteine holoenzyme Homo sapiens
0.13
-
L-cysteine heavy subunit Homo sapiens
0.15
-
L-cysteine
-
Proteus mirabilis
0.16
-
ATP
-
Proteus mirabilis
0.19
-
L-cysteine
-
Nicotiana tabacum
0.2
-
ATP
-
[Candida] boidinii
0.2
-
L-cysteine strain KM Escherichia coli
0.2
-
ATP holoenzyme Rattus norvegicus
0.2
-
L-cysteine heavy subunit and holoenzyme Rattus norvegicus
0.24
-
L-glutamate
-
Trypanosoma brucei
0.31
-
L-alpha-aminobutyrate
-
Ascaris suum
0.4
-
L-cysteine
-
[Candida] boidinii
0.4
-
ATP holoenzyme Homo sapiens
0.41
-
L-cysteine
-
Ascaris suum
0.5
-
L-glutamate strain B Escherichia coli
0.69
-
L-cysteine
-
Trypanosoma brucei
0.7
-
L-glutamate strain W Escherichia coli
0.71
-
ATP
-
Trypanosoma brucei
0.94
-
L-glutamate
-
Ascaris suum
1
-
L-alpha-aminobutyrate
-
Rattus norvegicus
1.3
-
L-alpha-aminobutyrate
-
Escherichia coli
1.4
-
L-glutamate
-
[Candida] boidinii
1.4
-
L-glutamate holoenzyme Rattus norvegicus
1.41
-
ATP
-
Ascaris suum
1.6
-
L-glutamate
-
Proteus mirabilis
1.7
-
L-glutamate strain KM Escherichia coli
1.9
-
L-glutamate holoenzyme Homo sapiens
2.3
-
L-alpha-aminobutyrate
-
Homo sapiens
3.2
-
L-glutamate heavy subunit Homo sapiens
7.3
-
(R)-beta-amino-iso-butyrate
-
Bos taurus
10.4
-
L-glutamate
-
Nicotiana tabacum
13.3
-
(S)-beta-amino-iso-butyrate
-
Bos taurus
18.2
-
L-glutamate heavy subunit Rattus norvegicus

Localization

Localization Comment Organism GeneOntology No. Textmining
cytosol exclusively Sus scrofa 5829
-
cytosol exclusively Bos taurus 5829
-
cytosol exclusively Ovis aries 5829
-
cytosol exclusively Homo sapiens 5829
-
cytosol exclusively Rattus norvegicus 5829
-
cytosol exclusively Mus musculus 5829
-

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required, bound to the erythrocyte enzyme Homo sapiens
Mg2+ required, bound to the kidney enzyme, involved in enzyme phosphorylation, can be substituted by Mn2+ by 25% Rattus norvegicus
Mg2+ required, bound to the kidney enzyme, involved in enzyme phosphorylation, can be substituted by Mn2+ by only 25% Rattus norvegicus
Mn2+ bound to the erythrocyte enzyme Homo sapiens
Mn2+ bound to the kidney enzyme, can substitute for Mg2+ by 25% Rattus norvegicus
Mn2+ bound to the kidney enzyme, can substitute for Mg2+ by only 25% Rattus norvegicus

Molecular Weight [Da]

Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
30500
-
1 * 72700, heavy catalytic subunit, + 1 * 30500, light regulatory subunit, SDS-PAGE Mus musculus
30600
-
1 * 72600, heavy catalytic subunit, + 1 * 30600, light regulatory subunit, SDS-PAGE Rattus norvegicus
30700
-
1 * 72800, heavy catalytic subunit, + 1 * 30700, light regulatory subunit, SDS-PAGE Homo sapiens
31000
-
1 * 73000, about, heavy catalytic subunit, + 1 * 31000, about, light regulatory subunit, SDS-PAGE Sus scrofa
31000
-
1 * 73000, about, heavy catalytic subunit, + 1 * 31000, about, light regulatory subunit, SDS-PAGE Bos taurus
31000
-
1 * 73000, about, heavy catalytic subunit, + 1 * 31000, about, light regulatory subunit, SDS-PAGE Ovis aries
34000
-
2 * 34000 Nicotiana tabacum
49300
-
x * 49300, catalytic subunit Acidithiobacillus ferrooxidans
58200
-
1 * 58200 Escherichia coli
59900
-
1 * 59900, catalytic unit Arabidopsis thaliana
60000
-
2 * 60000, SDS-PAGE [Candida] boidinii
60000
-
1 * 60000, about Proteus mirabilis
71400
-
x * 71400, catalytic subunit Schizosaccharomyces pombe
72600
-
1 * 72600, heavy catalytic subunit, + 1 * 30600, light regulatory subunit, SDS-PAGE Rattus norvegicus
72700
-
1 * 72700, heavy catalytic subunit, + 1 * 30500, light regulatory subunit, SDS-PAGE Mus musculus
72800
-
1 * 72800, heavy catalytic subunit, + 1 * 30700, light regulatory subunit, SDS-PAGE Homo sapiens
73000
-
1 * 73000, about, heavy catalytic subunit, + 1 * 31000, about, light regulatory subunit, SDS-PAGE Sus scrofa
73000
-
1 * 73000, about, heavy catalytic subunit, + 1 * 31000, about, light regulatory subunit, SDS-PAGE Bos taurus
73000
-
1 * 73000, about, heavy catalytic subunit, + 1 * 31000, about, light regulatory subunit, SDS-PAGE Ovis aries
77500
-
1 * 77500, catalytic unit Trypanosoma brucei
78100
-
1 * 78100, catalytic unit Leishmania tarentolae
78300
-
x * 78300, catalytic subunit Saccharomyces cerevisiae
100000
-
kidney enzyme, native PAGE Rattus norvegicus

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + L-Glu + L-Cys Sus scrofa rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview ADP + phosphate + gamma-L-Glu-L-Cys
-
ir
ATP + L-Glu + L-Cys Bos taurus rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview ADP + phosphate + gamma-L-Glu-L-Cys
-
ir
ATP + L-Glu + L-Cys Ovis aries rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview ADP + phosphate + gamma-L-Glu-L-Cys
-
ir
ATP + L-Glu + L-Cys Nicotiana tabacum rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview ADP + phosphate + gamma-L-Glu-L-Cys
-
ir
ATP + L-Glu + L-Cys Proteus mirabilis rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview ADP + phosphate + gamma-L-Glu-L-Cys
-
ir
ATP + L-Glu + L-Cys Ascaris suum rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview ADP + phosphate + gamma-L-Glu-L-Cys
-
ir
ATP + L-Glu + L-Cys [Candida] boidinii rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview ADP + phosphate + gamma-L-Glu-L-Cys
-
ir
ATP + L-Glu + L-Cys Xenopus sp. rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview ADP + phosphate + gamma-L-Glu-L-Cys
-
ir
ATP + L-Glu + L-Cys Saccharomyces cerevisiae rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview ADP + phosphate + gamma-L-Glu-L-Cys
-
ir
ATP + L-Glu + L-Cys Escherichia coli rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview ADP + phosphate + gamma-L-Glu-L-Cys
-
ir
ATP + L-Glu + L-Cys Trypanosoma brucei rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview ADP + phosphate + gamma-L-Glu-L-Cys
-
ir
ATP + L-Glu + L-Cys Arabidopsis thaliana rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview ADP + phosphate + gamma-L-Glu-L-Cys
-
ir
ATP + L-Glu + L-Cys Acidithiobacillus ferrooxidans rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview ADP + phosphate + gamma-L-Glu-L-Cys
-
ir
ATP + L-Glu + L-Cys Leishmania tarentolae rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview ADP + phosphate + gamma-L-Glu-L-Cys
-
ir
ATP + L-Glu + L-Cys Schizosaccharomyces pombe rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview ADP + phosphate + gamma-L-Glu-L-Cys
-
ir
ATP + L-Glu + L-Cys Rattus norvegicus rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview ADP + phosphate + gamma-L-Glu-L-Cys
-
ir
ATP + L-Glu + L-Cys Mus musculus rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview ADP + phosphate + gamma-L-Glu-L-Cys
-
ir
ATP + L-Glu + L-Cys Homo sapiens rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview ADP + phosphate + gamma-L-Glu-L-Cys
-
ir
additional information Sus scrofa GSH synthesis is controlled by the amount of enzyme, L-cysteine and by feedback inhibition exerted by GSH ?
-
?
additional information Bos taurus GSH synthesis is controlled by the amount of enzyme, L-cysteine and by feedback inhibition exerted by GSH ?
-
?
additional information Ovis aries GSH synthesis is controlled by the amount of enzyme, L-cysteine and by feedback inhibition exerted by GSH ?
-
?
additional information Mus musculus GSH synthesis is controlled by the amount of enzyme, L-cysteine and by feedback inhibition exerted by GSH ?
-
?
additional information Homo sapiens GSH synthesis is controlled by the amount of enzyme, L-cysteine and by feedback inhibition exerted by GSH, enzyme overexpression provides resistance to melphalan and other drugs, overview, protection of cancer cells by increased GSH levels ?
-
?
additional information Rattus norvegicus GSH synthesis is controlled by the amount of enzyme, L-cysteine and by feedback inhibition exerted by GSH, regulation by dephosphorylation/phosphorylation ?
-
?
additional information Trypanosoma brucei most of the GSH produced in this pathway is converted to trypanothione ?
-
?

Organism

Organism UniProt Comment Textmining
Acidithiobacillus ferrooxidans Q56277
-
-
Arabidopsis thaliana P46309
-
-
Ascaris suum
-
-
-
Bos taurus
-
-
-
Escherichia coli P0A6W9 strain W, strain B, strain KM
-
Homo sapiens P48506 heavy, catalytic subunit
-
Homo sapiens P48507 light, regulatory subunit
-
Leishmania tarentolae P90557
-
-
Mus musculus A0A0H2UNM8 light, regulatory subunit
-
Mus musculus P97494 heavy, catalytic subunit
-
Nicotiana tabacum
-
-
-
no activity in Entamoeba histolytica
-
-
-
no activity in Giardia sp.
-
-
-
Ovis aries
-
-
-
Proteus mirabilis
-
-
-
Rattus norvegicus P19468 heavy, catalytic subunit
-
Rattus norvegicus P48508 light, regulatory subunit
-
Saccharomyces cerevisiae P32477
-
-
Schizosaccharomyces pombe Q09768
-
-
Sus scrofa
-
-
-
Trypanosoma brucei Q26820
-
-
Xenopus sp.
-
-
-
[Candida] boidinii
-
-
-

Posttranslational Modification

Posttranslational Modification Comment Organism
phosphoprotein the heavy, catalytic subunit can be phosphorylated by dibutyrl cAMP in hepatocytes, and by protein kinase C, protein kinase A, and Ca2+/calmodulin-dpendent kinas II on serine and threonine residues in presence of Mg2+, regulatory role of dephosphorylation/phosphorylation in vivo Rattus norvegicus

Purification (Commentary)

Purification (Comment) Organism
-
Proteus mirabilis
-
Saccharomyces cerevisiae
-
Escherichia coli
from erythrocyte Ovis aries
from erythrocyte, from malignant astrocytoma cell line, recombinant from Escherichia coli to homogeneity Homo sapiens
from kidney, liver and erythrocytes, recombinant catalytic subunit and holoenzyme from Escherichia coli to homogeneity Rattus norvegicus
from lens Bos taurus
from liver Sus scrofa
from liver Xenopus sp.
from reproductive tissue Ascaris suum
partially Nicotiana tabacum
recombinant from Escherchia coli to homogeneity Trypanosoma brucei

Reaction

Reaction Comment Organism Reaction ID
ATP + L-glutamate + L-cysteine = ADP + phosphate + gamma-L-glutamyl-L-cysteine enzyme-bound reaction intermediate is a gamma-glutamyl-phosphate, active site cysteine, catalytic mechanism and substrate binding Bos taurus
ATP + L-glutamate + L-cysteine = ADP + phosphate + gamma-L-glutamyl-L-cysteine enzyme-bound reaction intermediate is a gamma-glutamyl-phosphate, active site cysteine, catalytic mechanism, active site and substrate binding, Lys38 is an active site residue in the glutamyl binding site, His150 is essential for activity Rattus norvegicus
ATP + L-glutamate + L-cysteine = ADP + phosphate + gamma-L-glutamyl-L-cysteine enzyme-bound reaction intermediate is a gamma-glutamyl-phosphate, active site cysteine, mechanism Sus scrofa
ATP + L-glutamate + L-cysteine = ADP + phosphate + gamma-L-glutamyl-L-cysteine enzyme-bound reaction intermediate is a gamma-glutamyl-phosphate, active site cysteine, mechanism Ovis aries
ATP + L-glutamate + L-cysteine = ADP + phosphate + gamma-L-glutamyl-L-cysteine enzyme-bound reaction intermediate is a gamma-glutamyl-phosphate, active site cysteine, mechanism Homo sapiens
ATP + L-glutamate + L-cysteine = ADP + phosphate + gamma-L-glutamyl-L-cysteine enzyme-bound reaction intermediate is a gamma-glutamyl-phosphate, active site cysteine, mechanism Mus musculus
ATP + L-glutamate + L-cysteine = ADP + phosphate + gamma-L-glutamyl-L-cysteine no conserved cysteine residue in the active site Escherichia coli
ATP + L-glutamate + L-cysteine = ADP + phosphate + gamma-L-glutamyl-L-cysteine no conserved cysteine residue in the active site Leishmania tarentolae

Source Tissue

Source Tissue Comment Organism Textmining
astrocytoma cell malignant cell line Homo sapiens
-
brain
-
Homo sapiens
-
brain
-
Rattus norvegicus
-
colon
-
Homo sapiens
-
erythrocyte
-
Ovis aries
-
erythrocyte
-
Homo sapiens
-
erythrocyte
-
Rattus norvegicus
-
heart
-
Homo sapiens
-
kidney
-
Sus scrofa
-
kidney
-
Bos taurus
-
kidney
-
Ovis aries
-
kidney
-
Homo sapiens
-
kidney
-
Rattus norvegicus
-
kidney
-
Mus musculus
-
lens
-
Bos taurus
-
liver
-
Sus scrofa
-
liver
-
Bos taurus
-
liver
-
Ovis aries
-
liver
-
Xenopus sp.
-
liver
-
Homo sapiens
-
liver
-
Rattus norvegicus
-
liver
-
Mus musculus
-
lung
-
Homo sapiens
-
macrophage
-
Mus musculus
-
additional information expression patterns of both subunits in the tissues, overview, 2 transcript different in size for both the heavy and light subunit occur in the tissues, some tumors overexpress only the heavy subunit rather than the holoenzyme Homo sapiens
-
additional information expression patterns of both subunits in the tissues, overview, 2 transcripts different in size for both the heavy and light subunit occur in the tissues, some tumors overexpress only the heavy subunit rather than the holoenzyme Homo sapiens
-
ovary
-
Homo sapiens
-
pancreas
-
Homo sapiens
-
peripheral blood
-
Homo sapiens
-
placenta
-
Homo sapiens
-
prostate
-
Homo sapiens
-
reproductive system
-
Ascaris suum
-
skeletal muscle
-
Homo sapiens
-
small intestine
-
Homo sapiens
-
spleen
-
Homo sapiens
-
testis
-
Homo sapiens
-
thymus
-
Homo sapiens
-

Specific Activity [micromol/min/mg]

Specific Activity Minimum [µmol/min/mg] Specific Activity Maximum [µmol/min/mg] Comment Organism
additional information
-
-
Rattus norvegicus
0.001
-
native COS cells Homo sapiens
0.013
-
-
[Candida] boidinii
0.014
-
transformed COS cells expressing both the recombinant subunits at equal amounts Homo sapiens
0.038
-
transformed COS cells expressing the recombinant catalytic subunit Homo sapiens
25
-
purified enzyme Rattus norvegicus
25
-
purified recombinant enzyme Homo sapiens

Storage Stability

Storage Stability Organism
-20°C, purified enzyme, 25% glycerol, indefinitely stable Sus scrofa
-20°C, purified enzyme, 25% glycerol, indefinitely stable Bos taurus
-20°C, purified enzyme, 25% glycerol, indefinitely stable Ovis aries
-20°C, purified enzyme, 25% glycerol, indefinitely stable Homo sapiens
-20°C, purified enzyme, 25% glycerol, indefinitely stable Rattus norvegicus
-80°C, enzyme is very stable at Escherichia coli
-80°C, enzyme is very stable at Arabidopsis thaliana

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + alpha-methyl-DL-glutamate + L-alpha-aminobutyrate
-
Rattus norvegicus ADP + phosphate + alpha-methyl-DL-glutamyl-L-alpha-aminobutyrate
-
ir
ATP + beta-glutamate + L-alpha-aminobutyrate
-
Rattus norvegicus ADP + phosphate + beta-glutamyl-L-alpha-aminobutyrate
-
ir
ATP + beta-methyl-DL-glutamate + L-alpha-aminobutyrate
-
Rattus norvegicus ADP + phosphate + beta-methyl-DL-glutamyl-L-alpha-aminobutyrate
-
ir
ATP + D-Glu + L-alpha-aminobutyrate
-
Rattus norvegicus ADP + phosphate + gamma-D-Glu-L-alpha-aminobutyrate
-
ir
ATP + DL-alpha-aminomethylglutarate + L-alpha-aminobutyrate
-
Rattus norvegicus ADP + phosphate + DL-alpha-aminomethylglutaryl-L-alpha-aminobutyrate
-
ir
ATP + DL-alpha-aminomethylsuccinate + L-alpha-aminobutyrate
-
Rattus norvegicus ADP + phosphate + DL-alpha-aminomethylsuccinyl-L-alpha-aminobutyrate
-
ir
ATP + DL-beta-aminoadipate + L-alpha-aminobutyrate
-
Rattus norvegicus ADP + phosphate + DL-beta-aminoadipyl-L-alpha-aminobutyrate
-
ir
ATP + L-Glu
-
Rattus norvegicus ADP + phosphate + 5-oxoproline
-
ir
ATP + L-Glu + (R)-beta-amino-iso-butyrate 2fold less reactive as the S-isomer Bos taurus ADP + phosphate + gamma-L-Glu-(R)-beta-amino-iso-butyrate
-
ir
ATP + L-Glu + (S)-beta-amino-iso-butyrate 2fold as reactive as the R-isomer Bos taurus ADP + phosphate + gamma-L-Glu-(S)-beta-amino-iso-butyrate
-
ir
ATP + L-Glu + beta-chloro-L-alanine
-
Rattus norvegicus ADP + phosphate + gamma-L-Glu-beta-chloro-L-alanine
-
ir
ATP + L-Glu + DL-allylglycine
-
Rattus norvegicus ADP + phosphate + gamma-L-Glu-DL-allylglycine
-
ir
ATP + L-Glu + DL-beta-amino-iso-butyrate
-
Rattus norvegicus ADP + phosphate + gamma-L-Glu-DL-beta-amino-iso-butyrate
-
ir
ATP + L-Glu + Gly
-
Rattus norvegicus ADP + phosphate + gamma-L-Glu-Gly
-
ir
ATP + L-Glu + L-2-aminobutanoate
-
Escherichia coli ADP + phosphate + gamma-L-Glu-2-aminobutanoate
-
?
ATP + L-Glu + L-alanine
-
Rattus norvegicus ADP + phosphate + gamma-L-Glu-L-alanine
-
ir
ATP + L-Glu + L-alpha-aminobutyrate
-
Bos taurus ADP + phosphate + gamma-L-Glu-L-alpha-aminobutyrate
-
ir
ATP + L-Glu + L-alpha-aminobutyrate
-
Ascaris suum ADP + phosphate + gamma-L-Glu-L-alpha-aminobutyrate
-
ir
ATP + L-Glu + L-alpha-aminobutyrate
-
Rattus norvegicus ADP + phosphate + gamma-L-Glu-L-alpha-aminobutyrate
-
ir
ATP + L-Glu + L-alpha-aminobutyrate
-
Homo sapiens ADP + phosphate + gamma-L-Glu-L-alpha-aminobutyrate
-
ir
ATP + L-Glu + L-alpha-aminoheptanoate
-
Rattus norvegicus ADP + phosphate + gamma-L-Glu-L-alpha-aminoheptanoate
-
ir
ATP + L-Glu + L-Cys
-
Sus scrofa ADP + phosphate + gamma-L-Glu-L-Cys
-
ir
ATP + L-Glu + L-Cys
-
Bos taurus ADP + phosphate + gamma-L-Glu-L-Cys
-
ir
ATP + L-Glu + L-Cys
-
Ovis aries ADP + phosphate + gamma-L-Glu-L-Cys
-
ir
ATP + L-Glu + L-Cys
-
Nicotiana tabacum ADP + phosphate + gamma-L-Glu-L-Cys
-
ir
ATP + L-Glu + L-Cys
-
Proteus mirabilis ADP + phosphate + gamma-L-Glu-L-Cys
-
ir
ATP + L-Glu + L-Cys
-
Ascaris suum ADP + phosphate + gamma-L-Glu-L-Cys
-
ir
ATP + L-Glu + L-Cys
-
[Candida] boidinii ADP + phosphate + gamma-L-Glu-L-Cys
-
ir
ATP + L-Glu + L-Cys
-
Xenopus sp. ADP + phosphate + gamma-L-Glu-L-Cys
-
ir
ATP + L-Glu + L-Cys
-
Saccharomyces cerevisiae ADP + phosphate + gamma-L-Glu-L-Cys
-
ir
ATP + L-Glu + L-Cys
-
Escherichia coli ADP + phosphate + gamma-L-Glu-L-Cys
-
ir
ATP + L-Glu + L-Cys
-
Rattus norvegicus ADP + phosphate + gamma-L-Glu-L-Cys
-
ir
ATP + L-Glu + L-Cys
-
Trypanosoma brucei ADP + phosphate + gamma-L-Glu-L-Cys
-
ir
ATP + L-Glu + L-Cys
-
Arabidopsis thaliana ADP + phosphate + gamma-L-Glu-L-Cys
-
ir
ATP + L-Glu + L-Cys
-
Acidithiobacillus ferrooxidans ADP + phosphate + gamma-L-Glu-L-Cys
-
ir
ATP + L-Glu + L-Cys
-
Leishmania tarentolae ADP + phosphate + gamma-L-Glu-L-Cys
-
ir
ATP + L-Glu + L-Cys
-
Mus musculus ADP + phosphate + gamma-L-Glu-L-Cys
-
ir
ATP + L-Glu + L-Cys
-
Schizosaccharomyces pombe ADP + phosphate + gamma-L-Glu-L-Cys
-
ir
ATP + L-Glu + L-Cys
-
Homo sapiens ADP + phosphate + gamma-L-Glu-L-Cys
-
ir
ATP + L-Glu + L-Cys rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview Sus scrofa ADP + phosphate + gamma-L-Glu-L-Cys
-
ir
ATP + L-Glu + L-Cys rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview Bos taurus ADP + phosphate + gamma-L-Glu-L-Cys
-
ir
ATP + L-Glu + L-Cys rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview Ovis aries ADP + phosphate + gamma-L-Glu-L-Cys
-
ir
ATP + L-Glu + L-Cys rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview Nicotiana tabacum ADP + phosphate + gamma-L-Glu-L-Cys
-
ir
ATP + L-Glu + L-Cys rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview Proteus mirabilis ADP + phosphate + gamma-L-Glu-L-Cys
-
ir
ATP + L-Glu + L-Cys rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview Ascaris suum ADP + phosphate + gamma-L-Glu-L-Cys
-
ir
ATP + L-Glu + L-Cys rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview [Candida] boidinii ADP + phosphate + gamma-L-Glu-L-Cys
-
ir
ATP + L-Glu + L-Cys rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview Xenopus sp. ADP + phosphate + gamma-L-Glu-L-Cys
-
ir
ATP + L-Glu + L-Cys rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview Saccharomyces cerevisiae ADP + phosphate + gamma-L-Glu-L-Cys
-
ir
ATP + L-Glu + L-Cys rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview Escherichia coli ADP + phosphate + gamma-L-Glu-L-Cys
-
ir
ATP + L-Glu + L-Cys rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview Trypanosoma brucei ADP + phosphate + gamma-L-Glu-L-Cys
-
ir
ATP + L-Glu + L-Cys rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview Arabidopsis thaliana ADP + phosphate + gamma-L-Glu-L-Cys
-
ir
ATP + L-Glu + L-Cys rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview Acidithiobacillus ferrooxidans ADP + phosphate + gamma-L-Glu-L-Cys
-
ir
ATP + L-Glu + L-Cys rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview Leishmania tarentolae ADP + phosphate + gamma-L-Glu-L-Cys
-
ir
ATP + L-Glu + L-Cys rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview Schizosaccharomyces pombe ADP + phosphate + gamma-L-Glu-L-Cys
-
ir
ATP + L-Glu + L-Cys rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview Rattus norvegicus ADP + phosphate + gamma-L-Glu-L-Cys
-
ir
ATP + L-Glu + L-Cys rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview Mus musculus ADP + phosphate + gamma-L-Glu-L-Cys
-
ir
ATP + L-Glu + L-Cys rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview Homo sapiens ADP + phosphate + gamma-L-Glu-L-Cys
-
ir
ATP + L-Glu + L-homocysteine
-
Rattus norvegicus ADP + phosphate + gamma-L-Glu-L-homocysteine
-
ir
ATP + L-Glu + L-homoserine
-
Rattus norvegicus ADP + phosphate + gamma-L-Glu-L-homoserine
-
ir
ATP + L-Glu + L-norleucine
-
Rattus norvegicus ADP + phosphate + gamma-L-Glu-L-norleucine
-
ir
ATP + L-Glu + L-norvaline
-
Rattus norvegicus ADP + phosphate + gamma-L-Glu-L-norvaline
-
ir
ATP + L-Glu + L-serine
-
Rattus norvegicus ADP + phosphate + gamma-L-Glu-L-serine
-
ir
ATP + L-Glu + L-threonine
-
Rattus norvegicus ADP + phosphate + gamma-L-Glu-L-threonine
-
ir
ATP + L-Glu + L-threonine allo-L-threonine is a 5fold better substrate than L-threonine Bos taurus ADP + phosphate + gamma-L-Glu-L-threonine
-
ir
ATP + L-Glu + S-methyl-L-cysteine
-
Rattus norvegicus ADP + phosphate + gamma-L-Glu-S-methyl-L-cysteine
-
ir
ATP + N-methyl-L-glutamate + L-alpha-aminobutyrate
-
Rattus norvegicus ADP + phosphate + N-methyl-L-glutamyl-L-alpha-aminobutyrate
-
ir
ATP + threo-beta-hydroxy-DL-glutamate + L-alpha-aminobutyrate
-
Rattus norvegicus ADP + phosphate + threo-beta-hydroxy-DL-glutamyl-L-alpha-aminobutyrate
-
ir
ATP + threo-gamma-hydroxy-L-glutamate + L-alpha-aminobutyrate
-
Rattus norvegicus ADP + phosphate + threo-gamma-hydroxy-L-glutamyl-L-alpha-aminobutyrate
-
ir
additional information substrate specificity Escherichia coli ?
-
?
additional information substrate specificity Homo sapiens ?
-
?
additional information substrate specificity, beta-alanine, (R,S)-beta-amino-n-butyrate, and (R,S)-alpha-ethyl-beta-alanine are no substrates Bos taurus ?
-
?
additional information the enzyme forms gamma-glutamyl-Tris in Tris buffers, substrate specificity, the L-glutamate analogues L-alpha-aminoadipate, L-asparate, glutarate, gamma-aminobutyrate, and gamma-methyl-DL-glutamate are poor substrates, beta-alanine, RS-beta-amino-n-butyrate, and RS-alpha-ethyl-beta-alanine are no substrates Rattus norvegicus ?
-
?
additional information GSH synthesis is controlled by the amount of enzyme, L-cysteine and by feedback inhibition exerted by GSH Sus scrofa ?
-
?
additional information GSH synthesis is controlled by the amount of enzyme, L-cysteine and by feedback inhibition exerted by GSH Bos taurus ?
-
?
additional information GSH synthesis is controlled by the amount of enzyme, L-cysteine and by feedback inhibition exerted by GSH Ovis aries ?
-
?
additional information GSH synthesis is controlled by the amount of enzyme, L-cysteine and by feedback inhibition exerted by GSH Mus musculus ?
-
?
additional information GSH synthesis is controlled by the amount of enzyme, L-cysteine and by feedback inhibition exerted by GSH, enzyme overexpression provides resistance to melphalan and other drugs, overview, protection of cancer cells by increased GSH levels Homo sapiens ?
-
?
additional information GSH synthesis is controlled by the amount of enzyme, L-cysteine and by feedback inhibition exerted by GSH, regulation by dephosphorylation/phosphorylation Rattus norvegicus ?
-
?
additional information most of the GSH produced in this pathway is converted to trypanothione Trypanosoma brucei ?
-
?

Subunits

Subunits Comment Organism
? x * 49300, catalytic subunit Acidithiobacillus ferrooxidans
? x * 71400, catalytic subunit Schizosaccharomyces pombe
? x * 78300, catalytic subunit Saccharomyces cerevisiae
dimer 2 * 60000, SDS-PAGE [Candida] boidinii
dimer 2 * 34000 Nicotiana tabacum
dimer 1 * 72600, heavy catalytic subunit, + 1 * 30600, light regulatory subunit, SDS-PAGE Rattus norvegicus
dimer 1 * 72700, heavy catalytic subunit, + 1 * 30500, light regulatory subunit, SDS-PAGE Mus musculus
dimer 1 * 72800, heavy catalytic subunit, + 1 * 30700, light regulatory subunit, SDS-PAGE Homo sapiens
dimer 1 * 73000, about, heavy catalytic subunit, + 1 * 31000, about, light regulatory subunit, SDS-PAGE Sus scrofa
dimer 1 * 73000, about, heavy catalytic subunit, + 1 * 31000, about, light regulatory subunit, SDS-PAGE Bos taurus
dimer 1 * 73000, about, heavy catalytic subunit, + 1 * 31000, about, light regulatory subunit, SDS-PAGE Ovis aries
monomer 1 * 58200 Escherichia coli
monomer 1 * 59900, catalytic unit Arabidopsis thaliana
monomer 1 * 60000, about Proteus mirabilis
monomer 1 * 77500, catalytic unit Trypanosoma brucei
monomer 1 * 78100, catalytic unit Leishmania tarentolae
More quarternary structure Ovis aries
More quarternary structure Mus musculus
More quarternary structure, the heavy subunit monomer may be essentially nonfunctional under physiological conditions Rattus norvegicus
More quarternary structure, the heavy subunit monomer may be essentially nonfunctional under physiological conditions Homo sapiens
More quaternary structure Sus scrofa
More quaternary structure Bos taurus
More quaternary structure Mus musculus
More the recombinant heavy subunit contains a 55 kDa insert which may function as the small subunit Trypanosoma brucei
More the recombinant heavy subunit contains a 55 kDa insert which may function as the small subunit Leishmania tarentolae

Synonyms

Synonyms Comment Organism
gamma-GCS
-
Sus scrofa
gamma-GCS
-
Bos taurus
gamma-GCS
-
Ovis aries
gamma-GCS
-
Nicotiana tabacum
gamma-GCS
-
Proteus mirabilis
gamma-GCS
-
Ascaris suum
gamma-GCS
-
[Candida] boidinii
gamma-GCS
-
Xenopus sp.
gamma-GCS
-
Saccharomyces cerevisiae
gamma-GCS
-
Escherichia coli
gamma-GCS
-
Rattus norvegicus
gamma-GCS
-
Trypanosoma brucei
gamma-GCS
-
Arabidopsis thaliana
gamma-GCS
-
Acidithiobacillus ferrooxidans
gamma-GCS
-
Leishmania tarentolae
gamma-GCS
-
Mus musculus
gamma-GCS
-
Schizosaccharomyces pombe
gamma-GCS
-
Homo sapiens
gamma-Glutamylcysteine synthetase
-
Sus scrofa
gamma-Glutamylcysteine synthetase
-
Bos taurus
gamma-Glutamylcysteine synthetase
-
Ovis aries
gamma-Glutamylcysteine synthetase
-
Nicotiana tabacum
gamma-Glutamylcysteine synthetase
-
Proteus mirabilis
gamma-Glutamylcysteine synthetase
-
Ascaris suum
gamma-Glutamylcysteine synthetase
-
[Candida] boidinii
gamma-Glutamylcysteine synthetase
-
Xenopus sp.
gamma-Glutamylcysteine synthetase
-
Saccharomyces cerevisiae
gamma-Glutamylcysteine synthetase
-
Escherichia coli
gamma-Glutamylcysteine synthetase
-
Rattus norvegicus
gamma-Glutamylcysteine synthetase
-
Trypanosoma brucei
gamma-Glutamylcysteine synthetase
-
Arabidopsis thaliana
gamma-Glutamylcysteine synthetase
-
Acidithiobacillus ferrooxidans
gamma-Glutamylcysteine synthetase
-
Leishmania tarentolae
gamma-Glutamylcysteine synthetase
-
Mus musculus
gamma-Glutamylcysteine synthetase
-
Schizosaccharomyces pombe
gamma-Glutamylcysteine synthetase
-
Homo sapiens

Cofactor

Cofactor Comment Organism Structure
ATP
-
Nicotiana tabacum
ATP
-
Proteus mirabilis
ATP
-
Ascaris suum
ATP
-
[Candida] boidinii
ATP
-
Xenopus sp.
ATP
-
Saccharomyces cerevisiae
ATP
-
Escherichia coli
ATP
-
Trypanosoma brucei
ATP
-
Arabidopsis thaliana
ATP
-
Acidithiobacillus ferrooxidans
ATP
-
Leishmania tarentolae
ATP
-
Schizosaccharomyces pombe
ATP the gamma-phosphate is located close to the glutamate binding site by the glycine-rich P-loop, built by the motif M(A/G)FGMGXXCLQ, to facilitate the formation of the enzyme-bound reaction intermediate gamma-glutamyl-phosphate Sus scrofa
ATP the gamma-phosphate is located close to the glutamate binding site by the glycine-rich P-loop, built by the motif M(A/G)FGMGXXCLQ, to facilitate the formation of the enzyme-bound reaction intermediate gamma-glutamyl-phosphate Bos taurus
ATP the gamma-phosphate is located close to the glutamate binding site by the glycine-rich P-loop, built by the motif M(A/G)FGMGXXCLQ, to facilitate the formation of the enzyme-bound reaction intermediate gamma-glutamyl-phosphate Ovis aries
ATP the gamma-phosphate is located close to the glutamate binding site by the glycine-rich P-loop, built by the motif M(A/G)FGMGXXCLQ, to facilitate the formation of the enzyme-bound reaction intermediate gamma-glutamyl-phosphate Homo sapiens
ATP the gamma-phosphate is located close to the glutamate binding site by the glycine-rich P-loop, built by the motif M(A/G)FGMGXXCLQ, to facilitate the formation of the enzyme-bound reaction intermediate gamma-glutamyl-phosphate Rattus norvegicus
ATP the gamma-phosphate is located close to the glutamate binding site by the glycine-rich P-loop, built by the motif M(A/G)FGMGXXCLQ, to facilitate the formation of the enzyme-bound reaction intermediate gamma-glutamyl-phosphate Mus musculus

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
additional information
-
additional information the Ki for GSH is tissue-dependent Rattus norvegicus
0.06
-
buthionine sulfone
-
Rattus norvegicus
0.11
-
GSH
-
Ascaris suum
0.15
-
L-buthionine-R-sulfoximine
-
Rattus norvegicus
0.42
-
GSH
-
Nicotiana tabacum
1
-
GSH heavy subunit Homo sapiens
1.1
-
GSH
-
Trypanosoma brucei
1.8
-
GSH heavy subunit Rattus norvegicus
1.8
-
GSH heavy subunit, the Ki for GSH is tissue-dependent Rattus norvegicus
2
-
GSH about, strain B Escherichia coli
2.3
-
GSH
-
Rattus norvegicus
2.3
-
GSH the Ki for GSH is tissue-dependent Rattus norvegicus
2.5
-
4-methylene-L-glutamate
-
Rattus norvegicus
2.7
-
S-sulfo-homocysteine
-
Rattus norvegicus
3.1
-
GSH
-
[Candida] boidinii
3.3
-
GSH holoenzyme Homo sapiens
4
-
GSH about, strain KM Escherichia coli
7.75
-
5-Chloro-4-oxo-L-norvaline
-
Rattus norvegicus
8.2
-
GSH holoenzyme Rattus norvegicus
12.5
-
ophthalmic acid noncompetitive Rattus norvegicus