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 | 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 | Comment | Organism | GeneOntology No. | Textmining |
---|
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Mg2+ | required | Mus musculus |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + L-glutamate + L-cysteine | Mus musculus | - |
ADP + phosphate + gamma-L-glutamyl-L-cysteine | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Mus musculus | P97494 AND O09172 | genes GCLC and GCLM encoding catalytic heavy chain subunit and modifier light chain subunits | - |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
macrophage | - |
Mus musculus | - |
RAW-264.7 cell | - |
Mus musculus | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + L-glutamate + L-cysteine | - |
Mus musculus | ADP + phosphate + gamma-L-glutamyl-L-cysteine | - |
? |
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 | Comment | Organism |
---|---|---|
gamma-glutamylcysteine synthase | - |
Mus musculus |
GCL | - |
Mus musculus |
glutamate-cysteine-ligase | - |
Mus musculus |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
ATP | - |
Mus musculus |
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 | 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 |