AHK-Cu (Copper Tripeptide-3) vs Glutathione (GSH)

AHK-Cu (Copper Tripeptide-3)

AHK-Cu is a copper(II) complex of the synthetic tripeptide alanyl-histidyl-lysine, a close relative of the naturally occurring GHK-Cu. The two differ only in the first residue: alanine here, glycine in GHK. GHK is found in human plasma and has a long history in the literature as a copper-binding peptide; AHK is a synthetic variant with the histidine in the same position. Published work on AHK-Cu is small and mostly in vitro, using cultured human dermal papilla cells and fibroblasts, and isolated hair follicles kept alive in organ culture. Controlled human studies are scarce, and much of the wider discussion of the compound borrows from GHK-Cu rather than from data on AHK-Cu itself.

Glutathione (GSH)

Glutathione is a tripeptide of glutamate, cysteine and glycine in which glutamate is linked through its side-chain (gamma) carboxyl group. It is made inside cells by two ATP-dependent enzymes, glutamate–cysteine ligase and glutathione synthetase, and is one of the most abundant small thiols in animal cells. It occurs in a reduced form (GSH) and an oxidised disulfide form (GSSG), and the ratio between them is widely used as a measure of cellular redox state. Its biochemistry inside the cell is well mapped. Studies that supply glutathione from outside, in animals or people, are harder to interpret because extracellular glutathione is readily broken down, and human findings in that area are inconsistent.

How AHK-Cu (Copper Tripeptide-3) acts

In GHK-Cu, the copper ion is held by the N-terminal amine, the deprotonated amide nitrogen between the first two residues and a nitrogen of the histidine imidazole ring. AHK is thought to bind copper in the same way, since its histidine sits in the same position. Copper-peptide complexes of this kind have been studied as carriers that deliver copper, a cofactor for enzymes such as lysyl oxidase and superoxide dismutase, to cells. In cultured human dermal papilla cells, AHK-Cu has been reported to affect cell proliferation and markers of apoptosis, including the balance of Bcl-2 and Bax. Which receptors or transporters mediate these observations has not been established.

How Glutathione (GSH) acts

The reactive part of glutathione is the thiol of its cysteine residue. Glutathione peroxidases use it to reduce hydrogen peroxide and lipid hydroperoxides, in the process oxidising two molecules of GSH to GSSG; glutathione reductase then regenerates GSH using NADPH. Glutathione S-transferases attach it to electrophilic compounds, the first step in a conjugation pathway that handles many drugs and foreign chemicals. It also forms mixed disulfides with cysteine residues in proteins, a modification studied as a form of redox signalling. Because the gamma-glutamyl bond resists most peptidases, breakdown begins with gamma-glutamyl transpeptidase on the outer surface of cells.

The records side by side

• Type: AHK-Cu (Copper Tripeptide-3), Copper tripeptide complex; Glutathione (GSH), Tripeptide
• Length: AHK-Cu (Copper Tripeptide-3), 3 amino acids; Glutathione (GSH), 3 amino acids
• Molecular weight: AHK-Cu (Copper Tripeptide-3), 451.39 g/mol; Glutathione (GSH), 307.33 g/mol
• Molecular formula: AHK-Cu (Copper Tripeptide-3), C15H24ClCuN6O4-; Glutathione (GSH), C10H17N3O6S

Reading a comparison

A comparison places two records side by side; it does not merge them. Each description above is drawn from that compound's own record, and the two were not necessarily characterised by the same methods, at the same time, or to the same level of detail. Before comparing any attribute, it is worth establishing that both records describe the substance you think they describe — names are not identifiers, and two entries sharing a name can differ in salt form, stereochemistry or the convention used to state a mass. Where a figure carries no method beside it, the comparison is between two reported numbers rather than between two measurements.