Glutamate cysteine ligase
Glutamate cysteine ligase (GCL) is the enzyme that carries out the first and rate-limiting step of glutathione synthesis, joining glutamate to cysteine. Its activity and the supply of cysteine are the two key controls on how much glutathione a cell makes.
Also called GCL, gamma-glutamylcysteine synthetase.
GCL is built from two parts, a catalytic subunit (GCLC) and a modifier subunit (GCLM), and the second enzyme of the pathway, glutathione synthetase, finishes the job (Lu 2013). Glutathione itself feeds back to slow GCL, which helps cells keep their levels within a range.
Cells adjust GCL through several transcription factors, among them Nrf2, AP-1 and NF-kB (Lu 2013). Because the enzyme is limited by how much cysteine the cell can take up, helping cells take in cysteine lets it work at its best, the mechanism proposed for lipoic acid (Han 1997).
Sources
- Lu SC. Glutathione synthesis. Biochim Biophys Acta 2013.
- Han D, Handelman G, Marcocci L et al. Lipoic acid increases de novo synthesis of cellular glutathione by improving cystine utilization. Biofactors 1997.
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