Literature summary for 6.3.2.2 extracted from

Franklin, C.C.; Backos, D.S.; Mohar, I.; White, C.C.; Forman, H.J.; Kavanagh, T.J.
Structure, function, and post-translational regulation of the catalytic and modifier subunits of glutamate cysteine ligase (2008), Mol. Aspects Med., 30, 86-98.

Search for more literature for 6.3.2.2

Activating Compound

Activating Compound	Comment	Organism	Structure
additional information	subunit GCLM increases the Vmax and Kcat of subunit GCLC, and decreases the Km for glutamate and ATP	Mus musculus
additional information	subunit GCLM increases the Vmax and Kcat of subunit GCLC, and decreases the Km for glutamate and ATP	Homo sapiens
additional information	subunit GCLM increases the Vmax and Kcat of subunit GCLC, and decreases the Km for glutamate and ATP	Rattus norvegicus

Protein Variants

Protein Variants	Comment	Organism
additional information	construction of Gclc and Gclm transgenic mice designed to conditionally overexpress GCL in the liver, conditional Gcl transgene expression in these mice promotes resistance to acetaminophen-induced liver injury	Mus musculus
additional information	GCLC and GCLM polymorphisms increase disease susceptibility in humans, overview	Homo sapiens

Inhibitors

Inhibitors	Comment	Organism	Structure
buthionine sulfoximine	GCL mediates the phosphorylation of buthionine sulfoximine, which is required for its tight and irreversible binding to the active site of GCL	Homo sapiens
buthionine sulfoximine	GCL mediates the phosphorylation of buthionine sulfoximine, which is required for its tight and irreversible binding to the active site of GCL	Mus musculus
buthionine sulfoximine	GCL mediates the phosphorylation of buthionine sulfoximine, which is required for its tight and irreversible binding to the active site of GCL	Rattus norvegicus
glutathione	feedback inhibition, subunit GCLM increases the Ki for GSH-mediated feedback inhibition of GCL, competitive to glutamate	Homo sapiens
glutathione	feedback inhibition, subunit GCLM increases the Ki for GSH-mediated feedback inhibition of GCL, competitive to glutamate	Mus musculus
glutathione	feedback inhibition, subunit GCLM increases the Ki for GSH-mediated feedback inhibition of GCL, competitive to glutamate	Rattus norvegicus
additional information	oxidative stress dramatically affects GCL holoenzyme formation and activity	Homo sapiens
additional information	oxidative stress dramatically affects GCL holoenzyme formation and activity	Mus musculus
additional information	oxidative stress dramatically affects GCL holoenzyme formation and activity	Rattus norvegicus

Localization

Localization	Comment	Organism	GeneOntology No.	Textmining
cytosol	-	Mus musculus	5829	-
cytosol	-	Homo sapiens	5829	-
cytosol	-	Rattus norvegicus	5829	-
membrane	-	Mus musculus	16020	-
membrane	-	Homo sapiens	16020	-
membrane	-	Rattus norvegicus	16020	-
mitochondrion	-	Mus musculus	5739	-
mitochondrion	-	Homo sapiens	5739	-
mitochondrion	-	Rattus norvegicus	5739	-
additional information	while GCLC and GCLM are generally considered to be cytosolic proteins there is evidence that they may exhibit altered subcellular localization in certain circumstances	Mus musculus	-	-
additional information	while GCLC and GCLM are generally considered to be cytosolic proteins there is evidence that they may exhibit altered subcellular localization in certain circumstances	Homo sapiens	-	-
additional information	while GCLC and GCLM are generally considered to be cytosolic proteins there is evidence that they may exhibit altered subcellular localization in certain circumstances	Rattus norvegicus	-	-

Metals/Ions

Metals/Ions	Comment	Organism	Structure
Mg2+	-	Arabidopsis thaliana
Mg2+	required	Drosophila melanogaster
Mg2+	required	Mus musculus
Mg2+	required	Homo sapiens
Mg2+	required	Rattus norvegicus

Molecular Weight [Da]

Molecular Weight [Da]	Molecular Weight Maximum [Da]	Comment	Organism
31000	-	1 * 73000, about, GCLC, + 1 * 31000, about, GCLM	Mus musculus
31000	-	1 * 73000, about, GCLC, + 1 * 31000, about, GCLM	Homo sapiens
31000	-	1 * 73000, about, GCLC, + 1 * 31000, about, GCLM	Rattus norvegicus
73000	-	1 * 73000, about, GCLC, + 1 * 31000, about, GCLM	Mus musculus
73000	-	1 * 73000, about, GCLC, + 1 * 31000, about, GCLM	Homo sapiens
73000	-	1 * 73000, about, GCLC, + 1 * 31000, about, GCLM	Rattus norvegicus

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
ATP + L-glutamate + L-cysteine	Drosophila melanogaster	-	ADP + phosphate + gamma-L-glutamyl-L-cysteine	-	?
ATP + L-glutamate + L-cysteine	Arabidopsis thaliana	-	ADP + phosphate + gamma-L-glutamyl-L-cysteine	-	?
ATP + L-glutamate + L-cysteine	Mus musculus	first rate-limiting step in GSH biosynthesis, GCL is a major determinant of cellular GSH levels, pathway overview	ADP + phosphate + gamma-L-glutamyl-L-cysteine	-	?
ATP + L-glutamate + L-cysteine	Homo sapiens	first rate-limiting step in GSH biosynthesis, GCL is a major determinant of cellular GSH levels, pathway overview	ADP + phosphate + gamma-L-glutamyl-L-cysteine	-	?
ATP + L-glutamate + L-cysteine	Rattus norvegicus	first rate-limiting step in GSH biosynthesis, GCL is a major determinant of cellular GSH levels, pathway overview	ADP + phosphate + gamma-L-glutamyl-L-cysteine	-	?
additional information	Mus musculus	post-translational regulation of GCL, overview	?	-	?
additional information	Rattus norvegicus	post-translational regulation of GCL, overview	?	-	?
additional information	Homo sapiens	post-translational regulation of GCL, overview. GCLC and GCLM polymorphisms increase disease susceptibility in humans, overview	?	-	?

Organism

Organism	UniProt	Comment	Textmining
Arabidopsis thaliana	-	-	-
Drosophila melanogaster	-	-	-
Homo sapiens	-	genes gclC and gclM encoding the two subunits of the enzyme	-
Mus musculus	-	genes gclC and gclM encoding the two subunits of the enzyme	-
Rattus norvegicus	-	genes gclC and gclM encoding the two subunits of the enzyme	-

Posttranslational Modification

Posttranslational Modification	Comment	Organism
lipoprotein	myristoylation is responsible for regulation of GCL subunit subcellular localization to membranes and mitochondria, overview	Mus musculus
lipoprotein	myristoylation is responsible for regulation of GCL subunit subcellular localization to membranes and mitochondria, overview	Homo sapiens
lipoprotein	myristoylation is responsible for regulation of GCL subunit subcellular localization to membranes and mitochondria, overview	Rattus norvegicus
additional information	post-translational modifications of GCLC, e.g. phosphorylation, myristoylation, caspase-mediated cleavage, have modest effects on GCL activity	Mus musculus
additional information	post-translational modifications of GCLC, e.g. phosphorylation, myristoylation, caspase-mediated cleavage, have modest effects on GCL activity	Homo sapiens
additional information	post-translational modifications of GCLC, e.g. phosphorylation, myristoylation, caspase-mediated cleavage, have modest effects on GCL activity	Rattus norvegicus
phosphoprotein	phosphorylation plays an important role in regulating GCL activity in vivo, phosphorylation of GCLC occurs on serine and threonine residues in vitro and the phosphorylation sites are likely identical for all three kinases protein kinase C, PKC, cAMP-dependent protein kinase, PKA, or Ca2+-calmodulin-dependent protein kinase II, CMKII	Mus musculus
phosphoprotein	phosphorylation plays an important role in regulating GCL activity in vivo, phosphorylation of GCLC occurs on serine and threonine residues in vitro and the phosphorylation sites are likely identical for all three kinases protein kinase C, PKC, cAMP-dependent protein kinase, PKA, or Ca2+-calmodulin-dependent protein kinase II, CMKII	Homo sapiens
phosphoprotein	phosphorylation plays an important role in regulating GCL activity in vivo, phosphorylation of GCLC occurs on serine and threonine residues in vitro and the phosphorylation sites are likely identical for all three kinases protein kinase C, PKC, cAMP-dependent protein kinase, PKA, or Ca2+-calmodulin-dependent protein kinase II, CMKII	Rattus norvegicus
proteolytic modification	caspase-mediated cleavage of GCLC, overview	Mus musculus
proteolytic modification	caspase-mediated cleavage of GCLC, overview	Homo sapiens
proteolytic modification	caspase-mediated cleavage of GCLC, overview	Rattus norvegicus

Source Tissue

Source Tissue	Comment	Organism	Textmining
hepatocyte	-	Mus musculus	-
hepatocyte	-	Rattus norvegicus	-
kidney	-	Rattus norvegicus	-
liver	-	Mus musculus	-
liver	-	Rattus norvegicus	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
ATP + L-glutamate + L-cysteine	-	Drosophila melanogaster	ADP + phosphate + gamma-L-glutamyl-L-cysteine	-	?
ATP + L-glutamate + L-cysteine	-	Arabidopsis thaliana	ADP + phosphate + gamma-L-glutamyl-L-cysteine	-	?
ATP + L-glutamate + L-cysteine	first rate-limiting step in GSH biosynthesis, GCL is a major determinant of cellular GSH levels, pathway overview	Mus musculus	ADP + phosphate + gamma-L-glutamyl-L-cysteine	-	?
ATP + L-glutamate + L-cysteine	first rate-limiting step in GSH biosynthesis, GCL is a major determinant of cellular GSH levels, pathway overview	Homo sapiens	ADP + phosphate + gamma-L-glutamyl-L-cysteine	-	?
ATP + L-glutamate + L-cysteine	first rate-limiting step in GSH biosynthesis, GCL is a major determinant of cellular GSH levels, pathway overview	Rattus norvegicus	ADP + phosphate + gamma-L-glutamyl-L-cysteine	-	?
ATP + L-glutamate + L-cysteine	GCL-mediated phosphorylation of L-glutamate creating the activated enzyme-bound gamma-glutamylphosphate intermediate	Mus musculus	ADP + phosphate + gamma-L-glutamyl-L-cysteine	-	?
ATP + L-glutamate + L-cysteine	GCL-mediated phosphorylation of L-glutamate creating the activated enzyme-bound gamma-glutamylphosphate intermediate	Homo sapiens	ADP + phosphate + gamma-L-glutamyl-L-cysteine	-	?
ATP + L-glutamate + L-cysteine	GCL-mediated phosphorylation of L-glutamate creating the activated enzyme-bound gamma-glutamylphosphate intermediate	Rattus norvegicus	ADP + phosphate + gamma-L-glutamyl-L-cysteine	-	?
additional information	post-translational regulation of GCL, overview	Mus musculus	?	-	?
additional information	post-translational regulation of GCL, overview	Rattus norvegicus	?	-	?
additional information	post-translational regulation of GCL, overview. GCLC and GCLM polymorphisms increase disease susceptibility in humans, overview	Homo sapiens	?	-	?
additional information	purified rat kidney GCL holoenzyme is capable of undergoing autophosphorylation, the phosphorylation is specific for the GCLC subunit, no phosphorylation of the GCLM subunit	Rattus norvegicus	?	-	?

Subunits

Subunits	Comment	Organism
dimer	1 * 73000, about, GCLC, + 1 * 31000, about, GCLM	Mus musculus
dimer	1 * 73000, about, GCLC, + 1 * 31000, about, GCLM	Homo sapiens
dimer	1 * 73000, about, GCLC, + 1 * 31000, about, GCLM	Rattus norvegicus
dimer	GCL reveals two redox-sensitive intramolecular disulfide bonds, CC1 and CC2, located at the homodimer interface that regulate plant GCL activity	Arabidopsis thaliana
More	GCL is a heterodimeric protein composed of catalytic GCLC and modifier GCLM subunits that are expressed from different genes, the catalytic subunit GCLC contains the active site responsible for the ATP-dependent bond formation between the amino group of cysteine and the gamma-carboxyl group of glutamate, the modifier subunit GCLM through direct interaction with GCLC acts to increase the catalytic efficiency of GCLC. GCL subunit protein structures, overview. GCLM is quite sensitive to aggregation in vitro in the absence of GCLC	Mus musculus
More	GCL is a heterodimeric protein composed of catalytic GCLC and modifier GCLM subunits that are expressed from different genes, the catalytic subunit GCLC contains the active site responsible for the ATP-dependent bond formation between the amino group of cysteine and the gamma-carboxyl group of glutamate, the modifier subunit GCLM through direct interaction with GCLC acts to increase the catalytic efficiency of GCLC. GCL subunit protein structures, overview. GCLM is quite sensitive to aggregation in vitro in the absence of GCLC	Homo sapiens
More	GCL is a heterodimeric protein composed of catalytic GCLC and modifier GCLM subunits that are expressed from different genes, the catalytic subunit GCLC contains the active site responsible for the ATP-dependent bond formation between the amino group of cysteine and the gamma-carboxyl group of glutamate, the modifier subunit GCLM through direct interaction with GCLC acts to increase the catalytic efficiency of GCLC. GCL subunit protein structures, overview. GCLM is quite sensitive to aggregation in vitro in the absence of GCLC	Rattus norvegicus
trimer	-	Drosophila melanogaster

Synonyms

Synonyms	Comment	Organism
gamma-glutamylcysteine ligase	-	Arabidopsis thaliana
GCL	-	Drosophila melanogaster
GCL	-	Mus musculus
GCL	-	Homo sapiens
GCL	-	Rattus norvegicus
GCL	-	Arabidopsis thaliana
glutamate cysteine ligase	-	Drosophila melanogaster
glutamate cysteine ligase	-	Mus musculus
glutamate cysteine ligase	-	Homo sapiens
glutamate cysteine ligase	-	Rattus norvegicus

Cofactor

Cofactor	Comment	Organism	Structure
ATP	-	Arabidopsis thaliana
ATP	required	Drosophila melanogaster
ATP	required	Mus musculus
ATP	required	Homo sapiens
ATP	required	Rattus norvegicus

Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.

Release 2023.1 (January 2023)