Antioxidants: y-glutamylcysteine

γ-glutamylcysteine (GGC) is the immediate precursor to the tripeptide glutathione, which is considered the “master” antioxidant for all aerobic organisms. Many human disorders and diseases such as Alzheimer’s, Parkinson’s – and ageing itself – are related to the body’s inability to maintain sufficient levels of glutathione within its cells.

It is widely thought in the scientific community that any treatment that can replenish glutathione levels in cells would offer broad therapeutic benefits. For many instances of chronic glutathione depletion, the problem lies with damaged regulatory control of the enzyme responsible for synthesising GGC (GGC synthetase) from glutamate and cysteine. That is, GGC becomes a limiting substrate for the final synthesis reaction catalysed by glutathione synthetase (condenses GGC with glycine to form glutathione).

There are only a few natural sources of GGC, with garlic, egg white and the whey fraction of milk having the highest amounts. High purity GGC has not been commercially available in sufficient quantities for widespread testing of its therapeutic potential. In 2006, my research group developed a biocatalytic process for GGC manufacture which we patent protected and licensed. The company is now manufacturing and commencing to sell GGC for cosmetic and dietary supplement applications in the US, where GGC has “GRAS” (generally regarded as safe) status.

As the next step towards demonstrating therapeutic benefits, we have recently completed and published a human clinical trial here at UNSW that has demonstrated that orally administered GGC can significantly increase glutathione levels in white blood cells, suggesting that GGC has systemic bioavailability. Further human clinical trials to explore any efficacy of GGC in the treatment of various diseases are being planned.

The 2018 Honours projects will continue our exploration of the therapeutic potential of GGC using human cell line and nematode models for glutathione depletion and oxidative stress. It is intended to publish any significant findings.

Oral administration of γ-glutamylcysteine increases intracellular glutathione levels above
homeostasis in a randomised human trial pilot study. Redox Biology, vol. 11, April 2017, pp.631-636.

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