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Literature summary for 6.3.2.2 extracted from

  • Akaboshi, T.; Yamanishi, R.
    Certain carotenoids enhance the intracellular glutathione level in a murine cultured macrophage cell line by inducing glutamate-cysteine-ligase (2014), Mol. Nutr. Food Res., 58, 1291-1300 .
    View publication on PubMed

Cloned(Commentary)

Cloned (Comment) Organism
genes gclc and gclm, encoding the two different subunits, the different genes are located on separate chromosomes, quantitative RT-PCR enzyme expression analysis Mus musculus

Inhibitors

Inhibitors Comment Organism Structure
buthionine sulfoximine an irreversible GCL inhibitor, abolishes the beta-carotene-induced GSH increase without affecting the beta-carotene-induced GCL protein expression Mus musculus
glutathione compared with the holoenzyme, the catalytic GCLc monomer shows lower enzymatic activity but higher sensitivity to feedback inhibition by GSH Mus musculus

Localization

Localization Comment Organism GeneOntology No. Textmining

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required Mus musculus

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + L-glutamate + L-cysteine Mus musculus
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ADP + phosphate + gamma-L-glutamyl-L-cysteine
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?

Organism

Organism UniProt Comment Textmining
Mus musculus P97494 AND O09172 genes GCLC and GCLM encoding catalytic heavy chain subunit and modifier light chain subunits
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Source Tissue

Source Tissue Comment Organism Textmining
macrophage
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Mus musculus
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RAW-264.7 cell
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Mus musculus
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Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + L-glutamate + L-cysteine
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Mus musculus ADP + phosphate + gamma-L-glutamyl-L-cysteine
-
?

Subunits

Subunits Comment Organism
heterodimer glutamate-cysteine ligase (GCL) is a heterodimer enzyme composed of a catalytic subunit (GCLC) and a modulator subunit (GCLM) Mus musculus

Synonyms

Synonyms Comment Organism
gamma-glutamylcysteine synthase
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Mus musculus
GCL
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Mus musculus
glutamate-cysteine-ligase
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Mus musculus

Cofactor

Cofactor Comment Organism Structure
ATP
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Mus musculus

Expression

Organism Comment Expression
Mus musculus enzyme induction in macrophages by beta-carotene or beta-cryptoxanthin. Both the protein and mRNA expression of GCL increases in a beta-carotene concentration-dependent manner. Buthionine sulfoximine, a GCL inhibitor, abolishes the beta-carotene-induced GSH increase without affecting the beta-carotene-induced GCL protein expression. Both cycloheximide, a translation inhibitor, and actinomycin D, a transcription inhibitor, completely suppressed the beta-carotene-induced GCL protein expression and the concomitant GSH increase. Similarly to beta-carotene, beta-cryptoxanthin upregulates the GCL protein expression, but lutein does not. The c-Jun N-terminal kinase (JNK) inhibitor, SP600125, suppresses the beta-carotene-induced GSH increase, whereas a p38 mitogen-activated protein kinase inhibitor or an extracellular signal-regulated kinase 1/2 inhibitor do not. The JNK inhibitor also suppresses the beta-carotene-induced GCL protein expression and consistently beta-carotene induced JNK phosphorylation up

General Information

General Information Comment Organism
metabolism certain carotenoids induce the Gcl mRNA expression in RAW264 cells and subsequently the GCL protein expression, which concomitantly enhances the intracellular GSH level, in a JNK pathway-related manner Mus musculus
physiological function glutathione (GSH) is synthesized by a two-step enzyme reaction. In the first step, L-cysteine is ligated to the gamma carboxyl group of L-glutamic acid by glutamate-cysteine-ligase (GCL, EC 6.3.2.2), and in the second step L-glycine is bound to gamma-glutamylcysteine by glutathione synthase (EC 6.3.2.3). The first step is the ratelimiting step. Compared with the holoenzyme, the catalytic GCLc monomer shows lower enzymatic activity but higher sensitivity to feedback inhibition by GSH. Involvement of GCL activity in the increase in the intracellular GSH level induced by beta-carotene Mus musculus