Nickel: the pathway in the body

Nickel is part of the pathway “Nickel”. This page shows the whole pathway; the station of Nickel is highlighted.

Where this laboratory value sits: Environmental nickel — food, water, air, skin. Nickel occurs in soils and plants and reaches the gut with food and drinking water. With dust in the air it reaches the lungs, and through contact with nickel-bearing metal the outermost layers of skin. Source 1

In brief

Nickel is a metal found in soils, plants and foods. In the body it is present as a divalent ion, binds to histidine and albumin and is excreted mainly by the kidney.

The pathway step by step

1. Environmental nickel → Divalent nickel In aqueous solution nickel is present mainly as a divalent ion. In this form it resembles iron and other divalent metals. Source 1, 2
2. Divalent nickel → Via iron transporters DMT1 The transporter DMT1 carries divalent iron into the gut cell. In doing so it also carries other divalent metals such as nickel. Source 3, 2
3. Via iron transporters → Nickel in the blood · Albumin In the blood nickel binds to the amino acid histidine and to a site at the start of the albumin chain made of aspartate, alanine and histidine. Source 4, 1
4. Nickel in the blood → Distribution in the body Through the blood nickel spreads into the tissues; it is found enriched in kidney, lung and skin, among others. Source 1, 5
5. Distribution in the body → Excretion in urine Nickel that has reached the blood is excreted mainly by the kidney. The part that is not absorbed leaves the gut with the stool. Source 5, 1
6. Into the cell → Binding to histidine Nickel binds preferentially to nitrogen atoms, for example to the side chain of the amino acid histidine in proteins; sulfur groups of glutathione bind it as well. Source 1, 2
7. Binding to histidine → Iron binding sites In enzymes that carry iron or zinc at their centre, nickel can occupy that place. The enzyme then works differently than with its own metal. Source 2
8. Into the cell → Binding to TLR4 Nickel ions bind to histidines of the receptor TLR4; two receptor molecules then join together and pass a signal into the cell. Source 6
9. Binding to TLR4 → Nickel as a hapten Nickel bound to the body's own proteins is seen by immune cells as an altered protein. A small substance acting in this way is called a hapten. Source 1, 6

Cofactors in this pathway

• Iron — Nickel uses the iron transporter DMT1 and can occupy the place of iron in enzymes Source 3, 2In the ORY catalogue as a laboratory value: Eisen
• Histidine — Amino acid that binds nickel through its nitrogen atom and keeps it dissolved in blood Source 1, 4In the ORY catalogue as a laboratory value: Histidin
• Albumin — Transport protein of the blood; binds nickel at a site near the start of its chain Source 4
• Glutathione — Binds nickel inside the cell through its sulfur group Source 1, 2In the ORY catalogue as a laboratory value: Glutathion (GSH)
• Zinc — In proteins nickel can bind at sites that otherwise carry zinc at their centre Source 2In the ORY catalogue as a laboratory value: Zink

Sources

1. Genchi G, Carocci A, Lauria G et al. Nickel: Human Health and Environmental Toxicology. Int J Environ Res Public Health 2020 · PubMed 31973020
2. Denkhaus E, Salnikow K. Nickel essentiality, toxicity, and carcinogenicity. Crit Rev Oncol Hematol 2002 · PubMed 11923067
3. Gunshin H, Mackenzie B, Berger UV et al. Cloning and characterization of a mammalian proton-coupled metal-ion transporter. Nature 1997 · PubMed 9242408
4. Laussac JP, Sarkar B. Characterization of the copper(II)- and nickel(II)-transport site of human serum albumin. Biochemistry 1984 · PubMed 6547847
5. Sunderman FW Jr, Hopfer SM, Sweeney KR et al. Nickel absorption and kinetics in human volunteers. Proc Soc Exp Biol Med 1989 · PubMed 2717626
6. Raghavan B, Martin SF, Esser PR et al. Metal allergens nickel and cobalt facilitate TLR4 homodimerization independently of MD2. EMBO Rep 2012 · PubMed 23059983

Whole pathway: Nickel

Related pathways

• Aluminium — into the cell
• Blei — Eisen, Glutathion (GSH)
• Cadmium — Eisen, Glutathion (GSH)
• Quecksilber — Glutathion (GSH), Zink

As of 2026-09-18. Draft, written by Claude to schema v2; sources checked in PubMed; expert approval pending
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