- 3
- Amino acids in GHK: glycine, histidine, lysine
- 1:1
- Copper to peptide in water at neutral acidity, 1982 study
- 42%
- Copper held by the peptide beside equal albumin, one test
The short answer
What is a copper peptide?
A copper peptide is a short chain of amino acids that holds on to a copper ion. Two names turn up on labels: GHK-Cu and AHK-Cu. The letters before the dash name the chain. The Cu after the dash means copper is attached.
GHK is three amino acids long: glycine, histidine and lysine. Chemists call a chain this short a tripeptide. It occurs naturally in blood plasma, and it binds copper(II) with high affinity [5].
That is the idea behind the name. This page covers what the studies measured about how the chain holds copper, how AHK-Cu differs, and what to check before you choose a product.
A short history
Where did GHK come from?
A 1980 paper in Nature reported a plasma tripeptide, written GHL in that paper. During its isolation from plasma, the tripeptide travelled with about an equal amount of copper [1].
The same paper measured copper uptake into cultured cells when the tripeptide was present. It also reported that the peptide formed complexes with copper(II) with ease [1].
A year later, Lau and Sarkar measured how copper(II) and GHK interact in a flask. They used titration and light absorption across a wide range of acidity [2].
In 1982, Freedman and colleagues used spectroscopy to work out the structure of the complex in water [3]. Later papers added detail, as the timeline shows.
- 1980
Plasma tripeptide isolated alongside copper
- 1981
Copper and GHK measured by titration
- 1982
Structure of the complex worked out in water
- 2001
GHK modified into a copper sensor
- 2011
X-ray and solution structures compared
- 2020
GHK, copper and urocanic acid found in one complex
Structure
How does the copper sit on the peptide?
Think of the peptide as a claw. The copper sits in the middle, and a few atoms on the chain hold it in place. Those atoms are nitrogens.
In 1982, spectroscopy of the complex in water found one copper per peptide at neutral acidity. One of the holding nitrogens sits in the ring of the histidine [3].
A 2011 study looked again with X-ray crystals and several kinds of spectroscopy. In water, the complex holds copper with three nitrogens. They come from the amino end of the chain, one amide and the histidine ring [5].
In the crystal, two complexes pair up. In water, they do not [5]. A crystal structure and a structure in water are different things, so it matters which one a paper measured.
The 2011 team also tested how easily copper comes loose. They used cyclic voltammetry, a method that applies a changing voltage to a sample. The GHK complex could be reduced to copper(I) at a strongly negative voltage, which released the copper ion [5].
Same compound, two settings
- Complexes pair up as dimers
- Oxygen atoms bridge the copper pairs
- A carboxylate oxygen fills the fourth spot
- One copper per peptide
- Three nitrogens hold the copper
- A single, separate complex
Binding
How tightly does GHK hold copper?
Lau and Sarkar compared GHK with two similar chains: glycyl-histidine and glycyl-histidyl-glycine. The lysine amino group raised the stability constants, which measure how tightly copper is held [2].
Lau and Sarkar found several different species in solution between pH 3.5 and 10.6. In other words, the form of the complex depends on acidity [2].
They also ran a dialysis test at pH 7.5 and 6 degrees C. GHK competed with albumin, a blood protein, for copper. With equal amounts of each, about 42% of the copper was bound to the peptide [2].
A 2001 paper used GHK as a tool. The authors attached a fluorescent group to the chain with standard solid-phase synthesis. Light output dropped when copper bound. Iron(II), cobalt, nickel and zinc caused very little change [4].
A 2020 study added a third partner. It found that GHK and cis-urocanic acid can bind one copper ion together. Chemists call that a ternary complex [6].
AHK-Cu
How is AHK-Cu different?
AHK-Cu follows the same pattern. Its chain is alanine, histidine and lysine. GHK has glycine in the first spot, and AHK has alanine. A 2007 paper by Pyo and colleagues names the compound L-alanyl-L-histidyl-L-lysine-Cu2+ [7].
That paper did not study structure. It used AHK-Cu in two lab systems: human hair follicles kept in culture, and cultured dermal papilla cells. The team measured follicle length and cell counts at very low concentrations [7].
Do not confuse AHK with DAHK. DAHK is a four-residue chain that starts with aspartic acid. The 2011 study found that copper swaps between DAHK chains very slowly, unlike GHK, where swapping was fast [5].
Most of the copper-binding work above was done on GHK, not AHK. No paper cited here measured how AHK holds copper. Do not assume the GHK numbers carry over.
The two names side by side
| GHK-Cu | AHK-Cu | |
|---|---|---|
| Chain | Glycine, histidine, lysine | Alanine, histidine, lysine |
| First amino acid | Glycine | Alanine |
| Papers cited here | Binding and structure | Cultured follicles and cells |
Before you choose
What should you check on the label and certificate?
Start with the name. GHK and GHK-Cu are not the same product. One is the bare chain. The other is the chain with copper attached.
Then read what the certificate reports. A lab report can list identity and purity of the peptide. Ask whether it says anything about the copper form. If it does not, the product page should not claim it.
Check that a report is posted for the product you are looking at. The certificate page lists what is posted, and the quality page explains how testing works. The supplier checklist covers the rest.
Each compound also has a short reference page: GHK-Cu and AHK-Cu. For unfamiliar terms, see the glossary.
- Does the name say GHK or GHK-Cu?
- Is a certificate posted for this product?
- Does it report identity and purity?
- Does it say anything about the copper form?
Questions
Common questions
What does the Cu in GHK-Cu mean?
Cu is the chemical symbol for copper. GHK-Cu is the three-amino-acid chain GHK with a copper ion attached.
Are GHK-Cu and AHK-Cu the same thing?
No. GHK starts with glycine and AHK starts with alanine. They are two different chains that each carry copper.
Is GHK the same as GHK-Cu?
No. GHK is the bare chain. GHK-Cu is the chain with copper attached.
Where can I find a certificate for a product?
Check the certificate page on this site. It lists the reports that are posted.