Kupfer (Cu): the pathway in the body · Biomarker & Blood Analysis

Kupfer (Cu) is part of the pathway “Copper”. This page shows the whole pathway; the station of Kupfer (Cu) is highlighted.

Where this laboratory value sits: Copper in food — mostly as Cu²⁺. In food, copper occurs mainly in the oxidised form Cu²⁺, bound to proteins. It is released from them in the stomach and upper small intestine. Food is the only source of copper. Source 1

In brief

Copper is a trace element that the body absorbs from food and distributes via the liver. In enzymes it transfers electrons, for example in the respiratory chain, in superoxide dismutase and in ceruloplasmin. Free copper is scarcely present in cells.

The pathway step by step

Each station states what the compound does there. Three signs: ↑ supplies — builds up or makes available · ↓ depletes — inhibits, consumes or withholds · ↕ both, depending on amount. Behind it stands what the statement rests on: established physiology, observed in studies, or contested. The signs do not grade; they name the direction.

1. Copper in food → Cu⁺ at the gut wall Reductases At the surface of the gut cells, reductases pass an electron to the copper. Only the reduced form Cu⁺ fits the transporter in the cell membrane. If little is reduced, less copper enters the cell. Source 1↑ supplies Reduction prepares uptake: only as Cu⁺ is copper recognised by the transporter CTR1. Cu⁺ is also the form in which copper is passed on inside the cell. established physiology Source 1
   ⚖ When the balance tips

   too much — If a lot of Cu⁺ is present at the gut wall, CTR1 brings more of it into the cell until the transporter is saturated; if copper in the cell rises, the cell withdraws CTR1 from the surface.

   too little — If little copper is reduced, less Cu⁺ reaches the transporter CTR1, and less copper enters the gut cell.

   established physiology · Source 1, 5

2. Cu⁺ at the gut wall → In the gut cell CTR1 CTR1 moves Cu⁺ into the gut cell. There, glutathione and the protein metallothionein bind the copper at once, so it is not present in free form in the cell. A lot of zinc makes more metallothionein form, which holds copper. Source 1, 5↕ both, depending on amount Glutathione and metallothionein keep copper bound, because free copper forms reactive compounds with oxygen. Once bound, it is either passed on to ATP7A or held back in the cell. established physiology Source 1, 5
   ⚖ When the balance tips

   too much — If copper builds up in the gut cell, metallothionein binds more of it. A lot of zinc makes more metallothionein form; this copper is lost with the shed cell instead of reaching the blood.

   too little — If little copper is in the gut cell, ATP7A releases less of it into the blood, and smaller amounts of copper reach the liver.

   established physiology · Source 6, 1

3. In the gut cell → Copper in the blood ATP7A · ATP The pump ATP7A releases copper from the gut cell into the blood. Bound to albumin and small molecules, it travels via the portal vein to the liver. It is thus not present in free form in the blood. Source 1↑ supplies Bound to albumin and small molecules, copper reaches the liver, which absorbs most of it. The binding holds the metal so that it is not present in free form in the blood. established physiology Source 1
   ⚖ When the balance tips

   too much — If copper in the blood rises, the liver absorbs more of it and releases the excess into the bile via ATP7B.

   too little — If little copper is in the blood, less reaches the liver and other tissues, and less copper is available for building into copper enzymes.

   established physiology · Source 1

4. Copper in the blood → Liver cell CTR1 The liver absorbs copper and distributes it onwards. What it does not use is released into the bile by the pump ATP7B; by this route copper leaves the body in the stool. If copper builds up, ATP7B releases more into the bile. Source 1↕ both, depending on amount The liver decides where copper goes: ATP7B builds it into ceruloplasmin or releases it into the bile. The bile is the main route by which the body gives off copper. established physiology Source 1
   ⚖ When the balance tips

   too much — If copper builds up in the liver cell, ATP7B moves to the side facing the bile ducts and releases more copper into the bile. If the pump cannot keep up, metallothionein binds the rest; unbound copper forms reactive oxygen species.

   too little — If little copper is in the liver cell, ATP7B stays at the Golgi apparatus; less copper goes into the bile, and what is present is mainly built into ceruloplasmin.

   established physiology · Source 1, 5

5. Liver cell → Ceruloplasmin ATP7B · ATP In the liver cell, ATP7B incorporates copper atoms into ceruloplasmin. This protein carries most of the copper in the blood and oxidises iron so that it can bind to transferrin. Without copper, ceruloplasmin is broken down quickly. Source 3↑ supplies Ceruloplasmin oxidises Fe²⁺ to Fe³⁺; only then can iron bind to transferrin and be passed on from the cells into the blood. established physiology Source 3
   ⚖ When the balance tips

   too much — If the liver makes more ceruloplasmin, for example during inflammatory processes, copper in the blood also rises, because this protein carries most of it.

   too little — If ceruloplasmin receives little copper, it is unstable and is broken down quickly; iron is then oxidised more slowly and can build up in tissues.

   established physiology · Source 3

6. Copper in the cell → CCS The chaperone CCS binds copper in the cytoplasm and hands it over to its target enzyme through direct contact. Only with this copper does SOD1 become active. Source 2↑ supplies CCS provides SOD1 with copper and helps to close a sulphur bridge in the enzyme; only then is SOD1 active. established physiology Source 2
   ⚖ When the balance tips

   too much — If copper is plentiful, CCS is broken down more quickly; the cell thus adjusts the copper supply to SOD1.

   too little — If little copper is available, more CCS is retained, but it can only pass on what it has bound itself; more SOD1 then remains without copper.

   established physiology · Source 2, 1

7. Copper in the cell → ATOX1 ATOX1 carries copper to the two copper pumps at the Golgi apparatus. From there it reaches new copper enzymes. Source 2, 5↑ supplies ATOX1 hands copper over to binding sites of the pumps ATP7A and ATP7B; through this handover the pumps receive the copper they move onwards. established physiology Source 2, 5
   ⚖ When the balance tips

   too much — If ATOX1 brings a lot of copper to the pumps, ATP7A and ATP7B leave the Golgi apparatus and release copper from the cell.

   too little — If little copper is bound to ATOX1, the pumps receive less, and fewer finished copper enzymes form in the vesicles.

   established physiology · Source 5, 2

8. Copper in the cell → COX17 COX17 and other helpers bring copper into the mitochondria, the power stations of the cell. There, cytochrome c oxidase receives its copper centres. Source 4↑ supplies COX17 passes copper on to the helpers SCO1, SCO2 and COX11, which build it into the copper centres of cytochrome c oxidase. established physiology Source 4
   ⚖ When the balance tips

   too much — More copper at COX17 does not make the respiratory chain faster if the copper centres of cytochrome c oxidase are already occupied.

   too little — If little copper is available, fewer cytochrome c oxidase molecules receive their copper centres, and the complex is assembled incompletely.

   established physiology · Source 4

9. CCS → SOD1 Superoxide dismutase 1 carries one copper and one zinc atom. It converts the oxygen radical superoxide into hydrogen peroxide and oxygen. If little copper is available, more SOD1 stays inactive. Source 2↓ depletes SOD1 removes the oxygen radical superoxide from the cell. The copper alternately accepts and gives up an electron; the zinc holds the enzyme in its shape. established physiology Source 2
   ⚖ When the balance tips

   too much — More copper does not make SOD1 faster if its copper site is already occupied; surplus copper is captured by metallothionein and glutathione.

   too little — If little copper is available, more SOD1 remains without copper and does not work; superoxide is then broken down more slowly.

   established physiology · Source 2, 1

10. ATOX1 → ATP7A and ATP7B The two pumps move copper into vesicles in which new copper enzymes are assembled. When copper levels rise, they move to the cell surface and release copper to the outside. The cell thus adjusts its copper content. Source 5, 1↕ both, depending on amount The pumps work in two directions: at the Golgi apparatus they supply copper to new enzymes; at the cell surface they release surplus copper and so lower the cell's copper content. established physiology Source 5, 1
    ⚖ When the balance tips

    too much — If copper in the cell rises, ATP7A and ATP7B move to the cell surface and release more copper to the outside; from the liver cell it goes into the bile.

    too little — If little copper is available, the pumps stay at the Golgi apparatus, and the copper present goes mainly into new copper enzymes.

    established physiology · Source 5, 1

11. COX17 → Cytochrome c oxidase Complex IV contains two copper centres. At the end of the respiratory chain they transfer electrons to oxygen, forming water. If little copper is available, fewer finished complexes form. Source 4↑ supplies Cytochrome c oxidase takes up the electrons at the end of the respiratory chain and pumps protons as it does so; the cell uses this gradient to make ATP. established physiology Source 4
    ⚖ When the balance tips

    too much — More copper does not speed up the complex if its two copper centres are already occupied.

    too little — If little copper is in the mitochondria, fewer complete complexes are built; the respiratory chain then passes fewer electrons to oxygen, and less ATP is formed.

    established physiology · Source 4

12. ATP7A and ATP7B → Copper enzymes In the vesicles, enzymes such as lysyl oxidase, which cross-links connective tissue fibres, and dopamine β-hydroxylase receive their copper atom. DBH converts dopamine to noradrenaline. Source 2, 1↑ supplies Lysyl oxidase links collagen and elastin fibres to each other. Dopamine β-hydroxylase converts dopamine to noradrenaline, with vitamin C as electron donor. established physiology Source 7, 1
    ⚖ When the balance tips

    too much — More copper does not make the finished enzymes faster, because their copper atom is already in place.

    too little — If little copper is available, fewer enzymes receive their copper atom; fibres are then cross-linked less often, and less noradrenaline is made from dopamine.

    established physiology · Source 1, 7

Further stations

• Copper in food — mostly as Cu²⁺ In food, copper occurs mainly in the oxidised form Cu²⁺, bound to proteins. It is released from them in the stomach and upper small intestine. Food is the only source of copper. Source 1↑ supplies Food is the body's only source of copper. Only once released from proteins can copper reach the gut wall; how much arrives there determines how much can enter the gut cell. established physiology Source 1
  ⚖ When the balance tips

  too much — If a lot of copper arrives, the liver releases more of it into the bile via ATP7B; it leaves the body with the stool.

  too little — If little copper arrives, the gut absorbs a larger share of it, and less copper leaves via the bile.

  established physiology · Source 1

• Copper in the cell — bound to glutathione Other cells also absorb copper via CTR1. Free copper is practically absent there: small transport proteins, the chaperones, receive it and deliver it to its destination. Free copper forms reactive oxygen species. Source 2, 5↑ supplies Because chaperones pass copper on in a targeted way, it reaches its enzymes without lying free in the cell. Free copper would occupy binding sites of other metals and form reactive compounds with oxygen. established physiology Source 2, 5
  ⚖ When the balance tips

  too much — If copper builds up in the cell, glutathione and metallothionein can no longer keep up; free copper forms reactive oxygen species and attaches to proteins. In cell culture this strains the cell.

  too little — If little copper is in the cell, the chaperones receive less, and some copper enzymes remain without their metal.

  observed in studies · Source 1, 5

Cofactors in this pathway

• Glutathione — Binds copper after uptake into the cell and hands it on to the chaperones; it thus does not lie free Source 1, 5In the ORY catalogue as a laboratory value: Glutathion (GSH)
• Zinc — Second metal of superoxide dismutase 1; stimulates metallothionein formation in intestinal cells; which holds copper Source 2, 6In the ORY catalogue as a laboratory value: Zink
• Iron — Oxidised by ceruloplasmin so that it can bind to transferrin; iron thus reaches the blood Source 3In the ORY catalogue as a laboratory value: Eisen
• Vitamin C — Electron donor for the copper-containing dopamine β-hydroxylase; the enzyme makes noradrenaline Source 7In the ORY catalogue as a laboratory value: Vitamin C (Ascorbinsäure)
• ATP — Energy source for the copper pumps ATP7A and ATP7B; they thus release copper Source 1, 5

What acts on this pathway

• Zinc — In gut cells, zinc stimulates the formation of metallothionein. This protein binds copper tightly inside the cell, so less of it passes into the blood. This relationship has been described. Source 6

Sources

1. Lutsenko S, Roy S, Tsvetkov P. Mammalian copper homeostasis: physiological roles and molecular mechanisms. Physiol Rev 2025 · PubMed 39172219
2. Robinson NJ, Winge DR. Copper metallochaperones. Annu Rev Biochem 2010 · PubMed 20205585
3. Hellman NE, Gitlin JD. Ceruloplasmin metabolism and function. Annu Rev Nutr 2002 · PubMed 12055353
4. Cobine PA, Pierrel F, Winge DR. Copper trafficking to the mitochondrion and assembly of copper metalloenzymes. Biochim Biophys Acta 2006 · PubMed 16631971
5. Lutsenko S. Dynamic and cell-specific transport networks for intracellular copper ions. J Cell Sci 2021 · PubMed 34734631
6. Avan A, Członkowska A, Gaskin S et al. The Role of Zinc in the Treatment of Wilson's Disease. Int J Mol Sci 2022 · PubMed 36012580
7. Prigge ST, Mains RE, Eipper BA et al. New insights into copper monooxygenases and peptide amidation: structure, mechanism and function. Cell Mol Life Sci 2000 · PubMed 11028916

Whole pathway: Copper

Related pathways

• 8-OHdG — Glutathion (GSH), Zink
• Mycotoxins — Glutathion (GSH), Zink
• Antioxidant capacity — Zink, Vitamin C (Ascorbinsäure)
• Borrelia — Zink, Eisen
• Calprotectin — Zink, Eisen

As of 2026-09-16. Draft written by Claude to schema v2; sources checked in PubMed; expert review pending
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