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Literature summary for 6.3.2.2 extracted from

  • Dickinson, D.A.; Iles, K.E.; Watanabe, N.; Iwamoto, T.; Zhang, H.; Krzywanski, D.M.; Forman, H.J.
    4-Hydroxynonenal induces glutamate cysteine ligase through JNK in HBE1 cells (2002), Free Radic. Biol. Med., 33, 974-987.
    View publication on PubMed
Search for more literature for 6.3.2.2

Activating Compound

Activating Compound Comment Organism Structure
4-hydroxy-2-nonenal 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 Homo sapiens
AP-1 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 Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + L-Glu + L-Cys Homo sapiens regulation and signaling in GSH de novo synthesis pathway ADP + phosphate + gamma-L-Glu-L-Cys
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 ?

Organism

Organism UniProt Comment Textmining
Homo sapiens
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 enzyme consists of a catalytic GCLC and a modulatory GCLM subunit encoded by 2 separate gcl genes
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Source Tissue

Source Tissue Comment Organism Textmining
cell culture
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 Homo sapiens
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HBE-1 cell immortalized bronchial epithelial cells from a healthy individual Homo sapiens
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Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + L-Glu + L-Cys combines glutamate and cysteine through the gamma carboxylmoiety rather than the alpha carboxyl moiety found in protein amide bonds, imparting resistance to proteolytic degradation Homo sapiens ADP + phosphate + gamma-L-Glu-L-Cys
-
 ?
ATP + L-Glu + L-Cys regulation and signaling in GSH de novo synthesis pathway Homo sapiens ADP + phosphate + gamma-L-Glu-L-Cys
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 ?

Subunits

Subunits Comment Organism
More enzyme consists of a catalytic GCLC and a modulatory GCLM subunit Homo sapiens

Synonyms

Synonyms Comment Organism
gamma-Glutamylcysteine synthetase
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 Homo sapiens
GCL
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 Homo sapiens
GCS
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 Homo sapiens

Cofactor

Cofactor Comment Organism Structure
ATP
-
 Homo sapiens