Center for Bioinformatics
Oxidoreductases | Transferases | Hydrolases | Lyases | Isomerases | Ligases

Basic Information

Enzyme Number

Official Name

glutamate---cysteine ligase

Name from literature

gamma-glutamylcysteine synthetase(gamma-GCShs)

Pathway from literature

glutathione synthesis

Pathway from KEGG

Metabolism of Other Amino Acids; Glutathione metabolism; map00480

Amino Acid Metabolism; Glutamate metabolism; map00251


Human (9606)

Genome localization

6p12[2729 ],


Can use L-aminohexanoate in place of glutamate.

Rate-limiting Description

"Glutamate cysteine ligase (GCL; also referred to as gamma-glutamylcysteine synthetase, GCS) catalyzes the rate-limiting step of glutathione synthesis." (11353135)

"OxLDL increased the intracellular levels of reactive oxygen species (ROS) and stimulated the expression of gamma-glutamylcysteine synthetase (gamma-GCS), the rate-limiting enzyme for the GSH synthesis, the mitogen-activated protein kinase (MAPK) activity, and the AP-1-DNA binding activity." (10218647)

Regulatory Information

Upstream transcription factor


Regulatory type


regulatory enzyme;

"gamma-Glutamylcysteine synthetase (gammaGCS) is a key regulatory enzyme in the synthesis of glutathione." (10623879)

transcriptional level;"TNF-alpha(7124),lens epithelium-derived growth factor(11168)"

"Results suggest that TNF-alpha elevates the expression of lens epithelium-derived growth factor (LEDGF) and that LEDGF is one of the transactivators of gamma-glutamylcysteine synthetase heavy subunit gene." (16403949)

signal pathway;

"Reduction-oxidation regulation of gamma-GCSh expression is mediated by p38 mitogen-activated protein kinase signaling." (15946948)

transcriptional level;Nrf2

"Recent experiments indicate that the bZip transcription factor Nrf2 participates in EpRE-mediated GCS subunit gene activation in combination with other bZip proteins" (10741850#16806086#10441483)

Gene ontology

Gene ontology

GO:0006536 (P) glutamate metabolic process [P48506 ];
GO:0004357 (F) glutamate-cysteine ligase activity [P48506 ];
GO:0000287 (F) magnesium ion binding [P48506 ];
GO:0043531 (F) ADP binding [P48506 ];
GO:0050880 (P) regulation of blood vessel size [P48506 ];
GO:0016595 (F) glutamate binding [P48506 ];
GO:0050662 (F) coenzyme binding [P48506 ];
GO:0009725 (P) response to hormone stimulus [P48506 ];
GO:0006979 (P) response to oxidative stress [P48506 ];
GO:0009408 (P) response to heat [P48506 ];
GO:0016481 (P) negative regulation of transcription [P48506 ];
GO:0006750 (P) glutathione biosynthetic process [P48506 ];
GO:0006916 (P) anti-apoptosis [P48506 ];
GO:0045454 (P) cell redox homeostasis [P48506 ];
GO:0006534 (P) cysteine metabolic process [P48506 ];

Disease relevance


Defects in GCLC are the cause of hemolytic anemia [MIM:230450] [P48506 ];




Entrez Gene




  Copyright 2009, Center for Bioinformatics 
  Last Modified: 2009-03-24  
  Design by Zhao Min