Gclc Protein plays an important role in the study of neurodegenerative diseases. This page provides comprehensive information about this topic, including its mechanisms, significance in disease processes, and therapeutic implications.
Gclc Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
| Protein Name | Glutamate-Cysteine Ligase Catalytic Subunit |
|---|---|
| Gene | GCLC |
| UniProt ID | P48506 |
| PDB ID | 1V48, 1V4F, 2NWW |
| Molecular Weight | 73.5 kDa |
| Subcellular Localization | Cytoplasm |
| Protein Family | ATP-grasp family, Ligases |
Glutamate-cysteine ligase (GCL) is a heterodimeric enzyme composed of a catalytic subunit (GCLC, 73.5 kDa) and a modifier subunit (GCLM, 30.8 kDa). GCLC contains the active site and ATP-binding domain, while GCLM modulates enzyme kinetics and sensitivity to inhibitors. The enzyme undergoes allosteric regulation and is feedback-inhibited by glutathione.
GCLC is the catalytic subunit of glutamate-cysteine ligase (also known as γ-glutamylcysteine synthetase), the rate-limiting enzyme in glutathione biosynthesis. This enzyme catalyzes the ATP-dependent formation of γ-glutamylcysteine from glutamate and cysteine:
Reaction: Glutamate + Cysteine + ATP → γ-Glutamylcysteine + ADP + Pi
The reaction is the rate-limiting step in glutathione (GSH) synthesis because GCLC has a low Km for cysteine and is subject to feedback inhibition by GSH. GCLC expression is regulated by:
In the nervous system, GCLC is expressed in neurons and glial cells, providing the foundation for glutathione-mediated antioxidant defense.
Griffith OW, et al. (1999). "The role of glutamate cysteine ligase in cellular glutathione synthesis." Free Radic Biol Med. 27(9-10):922-935. DOI:10.1016/S0891-5849(9900168-7
Dalton TP, et al. (2000). "Regulation of gamma-glutamylcysteine synthetase subunit gene expression: insights into transcriptional control of antioxidant defense." Toxicol Sci. 54(1):52-64. DOI:10.1093/toxsci/54.1.52
McBean GJ, et al. (2015). "Glutathione metabolism in brain and motor neuron disease." Cell Mol Neurobiol. 35(2):181-191. DOI:10.1007/s10571-014-0110-4
Gclc Protein plays an important role in the study of neurodegenerative diseases. This page provides comprehensive information about this topic, including its mechanisms, significance in disease processes, and therapeutic implications.
The study of Gclc Protein has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.