[3] GGC is synthesized from L-glutamic acid and L-cysteine in the cytoplasm of virtually all cells in an adenosine triphosphate (ATP)-requiring reaction catalyzed by the enzyme glutamate-cysteine ligase (GCL, EC 6.3.2.2; formerly γ-glutamylcysteine synthetase).

Mice that have had the glutamate-cysteine ligase (GCL) gene knocked out do not develop beyond the embryo stage and die before birth.

Such GGC supplementation may also be of benefit in situations where glutathione has been acutely lowered below optimum, such as following strenuous exercise, during trauma or episodes of poisoning.

The major drawback preventing the commercial success of chemical synthesis of GGC is the number of steps involved due to the three reactive groups on L-glutamic acid and L-cysteine molecules, which must be masked to achieve the correct regioisomer.

[20] In 1983, pioneers of glutathione research, Mary E. Anderson and Alton Meister, were the first to report on the ability of GGC to augment cellular GSH levels in a rat model.

Intact GGC, which was synthesised in their own laboratory, was shown to be taken up by cells, bypassing the rate-limiting step of the GCL enzyme to be converted to glutathione.