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Literature summary for 6.3.2.2 extracted from

  • Wild, A.C.; Mulcahy, R.T.
    Regulation of gamma-glutamylcysteine synthetase subunit gene expression: insights into transcriptional control of antioxidant defenses (2000), Free Radic. Res., 32, 281-301.
    View publication on PubMed

Activating Compound

Activating Compound Comment Organism Structure
1-(4-amino-2-methyl-5-pyridimidyl)-methyl-3-(2-chloroethyl)-3-nitrosurea induces expression of heavy subunit Homo sapiens
2,3-dimethoxy-1,4-naphthoquinone induces expression of heavy and light subunit Homo sapiens
2,3-dimethoxy-1,4-naphthoquinone induces expression of heavy and light subunit Rattus norvegicus
4-hydroxy-2-nonenal induces expression of heavy and light subunit Homo sapiens
6-Hydroxydopamine induces expression of heavy subunit Homo sapiens
adriamycin induces expression of heavy subunit Mus musculus
AP-1 transcription factor induces enzyme expression Mus musculus
AP-1 transcription factor induces enzyme expression Homo sapiens
AP-1 transcription factor induces enzyme expression Rattus norvegicus
apocynin induces expression of heavy subunit Homo sapiens
beta-naphthoflavone induces expression of heavy subunit Homo sapiens
buthionine sulfoximine induces expression of heavy and light subunit Homo sapiens
buthionine sulfoximine induces expression of heavy and light subunit Rattus norvegicus
butylated hydroxyanisole induces expression of heavy and light subunit Homo sapiens
butylated hydroxytoluene induces expression of heavy subunit Homo sapiens
cigarette smoke condensate induces expression of heavy subunit Homo sapiens
diethyl maleate induces expression of heavy and light subunit Homo sapiens
erythropoietin induces expression of heavy subunit Homo sapiens
Ethacrynic acid induces expression of heavy subunit Homo sapiens
ethoxyquin induces expression of heavy subunit Homo sapiens
H2O2 induces expression of heavy and light subunit Homo sapiens
interleukin-1 beta induces expression of heavy subunit Mus musculus
iodoacetamide induces expression of heavy subunit Homo sapiens
menadione induces expression of heavy and light subunit Homo sapiens
methylmercuric hydroxide induces expression of heavy subunit Mus musculus
methylmercuric hydroxide induces expression of heavy subunit Rattus norvegicus
additional information effect of miscellaneous treatments on enzyme mRNA expression, overview Rattus norvegicus
additional information ionization radiation induces expression of heavy subunit, effect of miscellaneous treatments on enzyme mRNA expression, overview Mus musculus
additional information 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 Homo sapiens
nitric oxide induces expression of heavy and light subunit via direct exposure or interleukin-1 induced Rattus norvegicus
oltipraz induces expression of heavy subunit Homo sapiens
oxidized low density lipoprotein induces expression of heavy subunit Homo sapiens
phorone induces expression of heavy subunit Homo sapiens
Prostaglandin A2 induces expression of heavy subunit Homo sapiens
pyrrolidine dithiocarbamate induces expression of heavy and light subunit Mus musculus
tert-butyl hydroquinone induces expression of heavy and light subunit Rattus norvegicus
tert-butylhydroquinone induces expression of heavy and light subunit Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
DNA sequence determination and analysis, 2 genes encode the 2 subunits, chromosomal mapping to 6p12 and 1p21, constitutive expression, expression of the heavy subunit alone or in combination with the light subunit in mammalian cells reveals that the regulatory subunit improves the activity, genetic regulation involving AP-1, overview, expression of several constructs in HepG2 cells, signaling for enzyme expression Homo sapiens
DNA sequence determination and analysis, genetic regulation involving AP-1, overview Saccharomyces cerevisiae
genetic regulation involving AP-1, constitutive expression, overview Rattus norvegicus
the 2 subunits are encoded by 2 different genes and are located on chromosomes 9D-E and 3HI-3, genetic regulation involving AP-1, constitutive expression, overview Mus musculus

Inhibitors

Inhibitors Comment Organism Structure
ciprofibrate inhibits expression of heavy subunit Rattus norvegicus
diquat inhibits expression of heavy subunit Rattus norvegicus
GSH feedback inhibition, acts on the heavy catalytic subunit Homo sapiens
GSH feedback inhibition, acts on the heavy catalytic subunit Mus musculus
GSH feedback inhibition, acts on the heavy catalytic subunit Rattus norvegicus
GSH feedback inhibition Saccharomyces cerevisiae
L-methionine inhibits expression of heavy subunit Rattus norvegicus
lipopolysaccharides inhibits expression of heavy subunit Rattus norvegicus
additional information protein-supplemented diet inhibits expression of heavy subunit Rattus norvegicus
NF-kappaB inhibits induction of enzyme expression by other substances, e.g. buthionine sulfoximine or tert-butylhydroquinone Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
additional information
-
additional information kinetics, recombinant enzyme Homo sapiens
1.4
-
L-glutamate holoenzyme Rattus norvegicus
18.2
-
L-glutamate catalytic subunit Rattus norvegicus

Metals/Ions

Metals/Ions Comment Organism Structure
Cu2+ induces expression of heavy subunit Homo sapiens
sodium arsenite induces expression of heavy subunit Homo sapiens
Zn2+ induces expression of heavy subunit Homo sapiens

Molecular Weight [Da]

Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
31000
-
1 * 73000, about, catalytic subunit, + 1 * 31000, about, regulatory subunit, SDS-PAGE Mus musculus
31000
-
1 * 73000, about, catalytic subunit, + 1 * 31000, about, regulatory subunit, SDS-PAGE Homo sapiens
31000
-
1 * 73000, about, catalytic subunit, + 1 * 31000, about, regulatory subunit, SDS-PAGE Rattus norvegicus
73000
-
1 * 73000, about, catalytic subunit, + 1 * 31000, about, regulatory subunit, SDS-PAGE Mus musculus
73000
-
1 * 73000, about, catalytic subunit, + 1 * 31000, about, regulatory subunit, SDS-PAGE Homo sapiens
73000
-
1 * 73000, about, catalytic subunit, + 1 * 31000, about, regulatory subunit, SDS-PAGE Rattus norvegicus
78200
-
-
Saccharomyces cerevisiae

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + L-Glu + L-Cys Mus musculus rate-limiting step in glutathione biosynthesis, regulation mechanism ADP + phosphate + gamma-L-Glu-L-Cys
-
ir
ATP + L-Glu + L-Cys Rattus norvegicus rate-limiting step in glutathione biosynthesis, regulation mechanism ADP + phosphate + gamma-L-Glu-L-Cys
-
ir
ATP + L-Glu + L-Cys Saccharomyces cerevisiae rate-limiting step in glutathione biosynthesis, regulation mechanism ADP + phosphate + gamma-L-Glu-L-Cys
-
ir
ATP + L-Glu + L-Cys Homo sapiens rate-limiting step in glutathione biosynthesis, regulation mechanism and model ADP + phosphate + gamma-L-Glu-L-Cys
-
ir

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
2 subunits encoded by 2 genes
-
Mus musculus
-
2 subunits encoded by 2 genes
-
Rattus norvegicus
-
2 subunits encoded by 2 genes
-
Saccharomyces cerevisiae
-
gene GSH1
-

Source Tissue

Source Tissue Comment Organism Textmining
erythrocyte
-
Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + L-Glu + L-Cys
-
Mus musculus 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
-
Rattus norvegicus 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 rate-limiting step in glutathione biosynthesis, regulation mechanism Mus musculus ADP + phosphate + gamma-L-Glu-L-Cys
-
ir
ATP + L-Glu + L-Cys rate-limiting step in glutathione biosynthesis, regulation mechanism Rattus norvegicus ADP + phosphate + gamma-L-Glu-L-Cys
-
ir
ATP + L-Glu + L-Cys rate-limiting step in glutathione biosynthesis, regulation mechanism Saccharomyces cerevisiae ADP + phosphate + gamma-L-Glu-L-Cys
-
ir
ATP + L-Glu + L-Cys rate-limiting step in glutathione biosynthesis, regulation mechanism and model Homo sapiens ADP + phosphate + gamma-L-Glu-L-Cys
-
ir

Subunits

Subunits Comment Organism
dimer 1 * 73000, about, catalytic subunit, + 1 * 31000, about, regulatory subunit, SDS-PAGE Mus musculus
dimer 1 * 73000, about, catalytic subunit, + 1 * 31000, about, regulatory subunit, SDS-PAGE Homo sapiens
dimer 1 * 73000, about, catalytic subunit, + 1 * 31000, about, regulatory subunit, SDS-PAGE Rattus norvegicus
monomer 1 * 78200 Saccharomyces cerevisiae
More the holoenzyme consists of a heavy catalytic and a light regulatory subunit, i.e. gamma-GCSh and gamma-GCSl Mus musculus
More the holoenzyme consists of a heavy catalytic and a light regulatory subunit, i.e. gamma-GCSh and gamma-GCSl Homo sapiens
More the holoenzyme consists of a heavy catalytic and a light regulatory subunit, i.e. gamma-GCSh and gamma-GCSl Rattus norvegicus

Synonyms

Synonyms Comment Organism
gamma-Glutamylcysteine synthetase
-
Mus musculus
gamma-Glutamylcysteine synthetase
-
Homo sapiens
gamma-Glutamylcysteine synthetase
-
Rattus norvegicus
GCS
-
Mus musculus
GCS
-
Homo sapiens
GCS
-
Rattus norvegicus
GLCL
-
Mus musculus
GLCL
-
Homo sapiens
GLCL
-
Rattus norvegicus
GSH1
-
Saccharomyces cerevisiae

Cofactor

Cofactor Comment Organism Structure
ATP
-
Mus musculus
ATP
-
Homo sapiens
ATP
-
Rattus norvegicus
ATP
-
Saccharomyces cerevisiae

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
1.8
-
GSH catalytic subunit Rattus norvegicus
8.2
-
GSH holoenzyme Rattus norvegicus