GHK-Cu

GHK-Cu (glycyl-L-histidyl-L-lysine:copper(II)) is a naturally occurring copper-binding tripeptide first identified in human plasma in 1973 by Loren Pickart. It consists of three amino acids — glycine, histidine, and lysine — complexed with a copper(II) ion at a 1:1 ratio. The peptide is found in plasma, saliva, and urine, with circulating levels that decline significantly with age: from approximately 200 ng/mL at age 20 to roughly 80 ng/mL by age 60.

GHK-Cu has attracted research interest for its unusually broad biological activity profile relative to its small size. It modulates the expression of over 4,000 human genes, representing roughly 6% of the genome, with a net effect that shifts gene expression patterns toward tissue repair, anti-inflammatory, and antioxidant states. It is commercially available in cosmetic formulations and remains under investigation for wound healing, tissue remodeling, and anti-aging applications.

GHK-Cu's mechanism of action is multifaceted and not fully attributable to a single receptor or pathway. The copper ion is essential — the GHK tripeptide without copper shows substantially reduced biological activity. The complex modulates several major signaling systems. It upregulates transforming growth factor beta (TGF-β) superfamily members involved in tissue repair and remodeling, while simultaneously suppressing TGF-β-driven fibrotic overresponses through a regulatory feedback mechanism that is not yet fully characterized.

At the gene expression level, GHK-Cu increases expression of DNA repair genes, ubiquitin-proteasome pathway components (enhancing clearance of damaged proteins), and antioxidant enzymes including superoxide dismutases and glutathione S-transferases. It promotes collagen synthesis, angiogenesis, and nerve growth while suppressing pro-inflammatory cytokines including IL-6 and TNF-α. The copper delivery function may also be significant — copper is a cofactor for lysyl oxidase (critical for collagen and elastin cross-linking), superoxide dismutase, and cytochrome c oxidase, suggesting GHK-Cu may serve as a physiological copper transport mechanism.