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Literature summary for 6.3.2.2 extracted from

  • Sikalidis, A.K.; Mazor, K.M.; Lee, J.I.; Roman, H.B.; Hirschberger, L.L.; Stipanuk, M.H.
    Upregulation of capacity for glutathione synthesis in response to amino acid deprivation: regulation of glutamate-cysteine ligase subunits (2014), Amino Acids, 46, 1285-1296.
    View publication on PubMedView publication on EuropePMC

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + L-glutamate + L-cysteine Mus musculus
-
ADP + phosphate + L-glutamyl-L-cysteine
-
?
ATP + L-glutamate + L-cysteine Homo sapiens
-
ADP + phosphate + L-glutamyl-L-cysteine
-
?
ATP + L-glutamate + L-cysteine Rattus norvegicus
-
ADP + phosphate + L-glutamyl-L-cysteine
-
?
ATP + L-glutamate + L-cysteine Rattus norvegicus Sprague-Dawley
-
ADP + phosphate + L-glutamyl-L-cysteine
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-
Mus musculus
-
-
-
Rattus norvegicus
-
-
-
Rattus norvegicus Sprague-Dawley
-
-
-

Source Tissue

Source Tissue Comment Organism Textmining
Hep-G2/C3A cell
-
Mus musculus
-
Hep-G2/C3A cell
-
Homo sapiens
-
liver
-
Rattus norvegicus
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + L-glutamate + L-cysteine
-
Mus musculus ADP + phosphate + L-glutamyl-L-cysteine
-
?
ATP + L-glutamate + L-cysteine
-
Homo sapiens ADP + phosphate + L-glutamyl-L-cysteine
-
?
ATP + L-glutamate + L-cysteine
-
Rattus norvegicus ADP + phosphate + L-glutamyl-L-cysteine
-
?
ATP + L-glutamate + L-cysteine
-
Rattus norvegicus Sprague-Dawley ADP + phosphate + L-glutamyl-L-cysteine
-
?

Subunits

Subunits Comment Organism
More the enzyme consists of a catalytic (GCLC) and a modifier (GCLM) subunit Mus musculus
More the enzyme consists of a catalytic (GCLC) and a modifier (GCLM) subunit Homo sapiens
More the enzyme consists of a catalytic (GCLC) and a modifier (GCLM) subunit Rattus norvegicus

Synonyms

Synonyms Comment Organism
GCL
-
Mus musculus
GCL
-
Homo sapiens
GCL
-
Rattus norvegicus

Cofactor

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

Expression

Organism Comment Expression
Homo sapiens actinomycin D and cycloheximide suppress enzyme expression down
Rattus norvegicus actinomycin D and cycloheximide suppress enzyme expression down
Mus musculus actinomycin D and cycloheximide suppress enzyme expression. Using GCLC knockout murine embryonic fibroblasts, addition of cysteine to catalytic subunit GCLC null cells results in a marked decrease in regulatory subunit GCLM mRNA levels despite the absence of GSH. Addition of GSH similarly reduces GCLM mRNA abundance down
Homo sapiens catalytic subunit GCLC protein levels do not increase, whereas regulatory subunit GCLM protein levels increase in the cells cultured in cysteine-deficient medium additional information
Homo sapiens both the glutamate-cysteine ligase catalytic (GCLC) and modifier (GCLM) subunit mRNA levels are upregulated in response to a lack of cysteine or other essential amino acids, independent of GSH levels up
Rattus norvegicus both the glutamate-cysteine ligase catalytic (GCLC) and modifier (GCLM) subunit mRNA levels are upregulated in response to a lack of cysteine or other essential amino acids, independent of GSH levels. In liver of rats fed sulfur amino acid-deficient diets, induction of ATF4 and phosphorylation of eIF2alpha are associated with higher levels of GCLC and GCLM mRNA up
Mus musculus both the glutamate-cysteine ligase catalytic (GCLC) and modifier (GCLM) subunit mRNA levels are upregulated in response to a lack of cysteine or other essential amino acids, independent of GSH levels. The upregulation does not occur in MEFs lacking GCN2, i.e. general control non-derepressible 2, also known as eIF2a kinase 4, or in cells expressing mutant eIF2alpha lacking the eIF2alpha kinase Ser51 phosphorylation site, indicating that expression of both GCLC and GCLM is mediated by the GCN2/ATF4 stress response pathway up

General Information

General Information Comment Organism
malfunction using GCLC knockout murine embryonic fibroblasts, addition of cysteine to catalytic subunit GCLC null cells results in a marked decrease in regulatory subunit GCLM mRNA levels despite the absence of GSH Mus musculus
physiological function expression of both glutamate-cysteine ligase catalytic and modifier subunit is mediated by the GCN2/ATF4 stress response pathway. Regulation of modifier subunit GCLM expression may be mediated by changes in the abundance of mRNA stabilizing or destabilizing proteins. Upregulation of GCLM levels in response to low cysteine levels may serve to protect the cell in the face of a future stress requiring GSH as an antioxidant or conjugating/detoxifying agent Mus musculus
physiological function expression of both glutamate-cysteine ligase catalytic and modifier subunit is mediated by the GCN2/ATF4 stress response pathway. Regulation of modifier subunit GCLM expression may be mediated by changes in the abundance of mRNA stabilizing or destabilizing proteins. Upregulation of GCLM levels in response to low cysteine levels may serve to protect the cell in the face of a future stress requiring GSH as an antioxidant or conjugating/detoxifying agent Homo sapiens
physiological function expression of both glutamate-cysteine ligase catalytic and modifier subunit is mediated by the GCN2/ATF4 stress response pathway. Regulation of modifier subunit GCLM expression may be mediated by changes in the abundance of mRNA stabilizing or destabilizing proteins. Upregulation of GCLM levels in response to low cysteine levels may serve to protect the cell in the face of a future stress requiring GSH as an antioxidant or conjugating/detoxifying agent Rattus norvegicus