Gamma-Glutamylcysteine

GCC

Gamma-glutamylcysteine (GGC) is a critical precursor to glutathione (GSH) with demonstrated systemic bioavailability and therapeutic potential in oxidative stress, aging, and disease contexts.

Biochemical Role of GGC

Gamma-glutamylcysteine (GGC) is a dipeptide and the immediate precursor to glutathione (GSH). Its intracellular concentration remains low due to rapid conversion to GSH via glycine addition, a reaction catalyzed by the ATP-dependent enzyme glutathione synthase (GS).

Essentiality and Age-Related Decline

GGC is essential for mammalian viability. Mice lacking the gene encoding glutamate-cysteine ligase (GCL), the enzyme that synthesizes GGC, die in embryogenesis due to an inability to produce GSH. In humans, GGC production declines with age and in many chronic diseases, prompting investigation into its supplementation as a strategy to restore glutathione levels. Additional proposed uses include recovery from acute GSH depletion caused by strenuous physical activity, trauma, or toxic exposure.

Therapeutic Potential

Reviews have examined GGC’s potential to restore GSH levels in aging and chronic diseases such as Alzheimer’s. GGC may also act as an antioxidant independently of its role in GSH synthesis.

Evidence from Clinical and Preclinical Studies

A human clinical study demonstrated that oral GGC significantly increases lymphocyte GSH levels, confirming systemic bioavailability. Animal studies support its therapeutic utility in mitigating oxidative damage, including in the brain, and in treating sepsis.

Limitations of GSH Supplementation

Direct GSH supplementation is ineffective at elevating intracellular GSH due to a steep extracellular–intracellular concentration gradient that prevents uptake. GGC, in contrast, may function as an intermediate in glutathione transport in multicellular organisms, although this remains unverified.

More Ingredients

GCC
GAA
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