Glutathione is a tripeptide (small protein) composed of the three amino acids glutamate, cysteine and glycine. It is made in each of the cells in your body by two sequential enzyme catalysed reactions. The first joins glutamate and cysteine to produce Glyteine (gamma glutamylcysteine) and the second adds the glycine to form glutathione. This process is essentially the same in the cells of all living organisms that use oxygen.
Without Glyteine, glutathione cannot be produced. Without enough Glyteine, insufficient glutathione will be produced to protect against oxidative stress.
Glutathione homeostasis is maintained in cells by a regulatory control process called feedback inhibition.
When glutathione concentrations are at homeostasis, the glutathione interacts with the enzyme glutamate cysteine ligase (GCL) to switch off its activity and thereby shut down the production of Glyteine. When the glutathione is used up and levels go below homeostasis, its interaction with GCL is weakened, the enzyme’s activity is switched on again leading to the renewed production of Glyteine, which fuels a return to glutathione homeostasis. All Glyteine inside the cell will be converted to glutathione by the unregulated enzyme glutathione synthetase (GS)
In this manner, glutathione regulates the production of Glyteine and indirectly controls its own homeostasis in cells.
The concentration of glutathione inside cells is directly related to the amount of Glyteine available inside cells for conversion into glutathione. In other words, glutathione homeostatic levels are dictated by the amount and rate of Glyteine production. If the GCL enzyme becomes dysfunctional as it often does in chronic disease, it will not make enough Glyteine to maintain a healthy glutathione homeostatis. As a consequence, the affected cells will suffer oxidative stress and its associated detrimental effects.