a. Glutathione Synthesis
For the body to produce Glutathione (GSH) six building blocks are required: L-glutamate, L-cysteine, L-glycine, magnesium, potassium, and 5' ATP. Two enzymes are also required and they are L-gamma-glutamyl-cysteine synthetase (equation 1) and glutathione synthetase (equation 2) and the reaction proceeds in the following manner:
(1) L-glutamate + L-cysteine + ATP--------->
L-gamma -glutamylcysteine + ADP + P
(2) L-gamma-glutamylcysteine + L-glycine +ATP----------->
L-gamma-glutamylcysteinylglycine +ADP + P
L-cysteine is the rate limiting substrate in this reaction12 , while the rate controlling enzyme for the reaction is L-gamma -glutamylcysteine synthetase(5).
b. Scavenger Pathways
The 2 major functions of glutathione are to detoxify hydrogen peroxide (H2O2) and other organoperoxidases (free radicals) and to defend against oxidation within cells via the Glutathione Redux Cycle, or more commonly referred to as the Scavenger Pathways(6,7).
Glutathione plays it's role of "scavenger" through out the body. The role of scavenger is primarily accomplished through glutathione peroxidase (GSH px). The peroxidase interacts with the H2O(2) to reduce it to harmless water, thus limiting it's electron stealing capacity. This is illustrated in the following equation:
(2) 2-glutathione-SH +ROOH ------>
glutathione disulfide + ROH + H2O
The disulfide is then reduced with the co-enzyme NADPH in the prescene of the enzyme Glutathione Reductase to yield the original glutathione compound.
(3) glutathione reductase +NADPH + H+ ----------->
2-glutathione-SH + NADP -
Many theories of aging and disease are based upon the interaction of the formation of free-radicals and the subsequent reduction in glutathione levels which allows for an accumulation of free-radicals to remain within a cell and organ or organ system. Free-radicals that remain within cells may cause cell damage, DNA damage and may even cause cell death, cancer transformation or loss of cell immunity to viral or bacterial infection.