Cadmium: the pathway in the body · Biomarker & Laboratory Analysis

This page shows the biochemical pathway of the substance Cadmium: how it enters the body, which stations it passes and which steps it affects. Every statement has a source. The page describes general textbook knowledge and says nothing about any individual person.

In brief

Cadmium is a heavy metal with no known role in the body. It enters cells via transport routes for iron and zinc, is bound to metallothionein and is stored mainly in liver and kidney. It leaves the body only very slowly.

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. Cadmium in food → Into the gut cell DMT1 · Iron, Zinc Cadmium ions use transporters for iron, zinc and manganese, mainly DMT1 and the zinc transporters ZIP8 and ZIP14. This is called ionic mimicry. It thus competes with iron and zinc. Source 1, 7, 6↑ supplies DMT1, ZIP8 and ZIP14 deliver cadmium into the gut cell because it resembles divalent metals such as iron and zinc. established physiology Source 1, 7, 6
   ⚖ When the balance tips

   too much — If there is a lot of cadmium in the gut, it competes with iron and zinc at these transporters.

   too little — If there is little cadmium in the gut, the transporters carry almost only their usual metals; if iron is scarce, more of them are made and they also absorb cadmium more readily.

   observed in studies · Source 7, 4

2. Into the gut cell → Cadmium in blood In blood, cadmium is first bound to albumin and other proteins. In this way it mainly reaches the liver. The liver absorbs most of it. Source 2↑ supplies Albumin and other blood proteins carry cadmium first to the liver, which absorbs most of it. established physiology Source 2
   ⚖ When the balance tips

   too much — If there is a lot of cadmium in the blood, more of it also reaches tissues other than the liver.

   too little — If there is little cadmium in the blood, the liver absorbs almost all of it.

   established physiology · Source 2

3. Cadmium in blood → Liver · Metallothionein In the liver, cadmium binds to metallothionein, a small protein with many cysteines. Part of this complex returns to the blood. Free cadmium is thus bound. Source 2, 3↓ depletes Metallothionein removes free cadmium from the cell interior and holds it tightly bound; part of the complex later returns to the blood and so reaches the kidney. established physiology Source 2, 3
   ⚖ When the balance tips

   too much — If more cadmium arrives than metallothionein can bind, free cadmium remains in the liver cell and binds to other proteins; in animal models the cell then makes more metallothionein.

   too little — If little metallothionein is present, cadmium is bound less tightly in the liver and stays free in the cell for longer.

   observed in studies · Source 3

4. Liver → Kidney Megalin, cubilin The cadmium-metallothionein complex is filtered in the kidney and taken back up in the first section of the renal tubules via the receptors megalin and cubilin. Cadmium thus accumulates in the kidney. Source 2, 1↑ supplies Via megalin and cubilin, the kidney draws the filtered cadmium-metallothionein complex back into the cells of the renal tubules; cadmium thus accumulates there instead of staying in the urine. established physiology Source 2, 1
   ⚖ When the balance tips

   too much — If a lot of the complex reaches the kidney, more of it is broken down in the cells of the renal tubules, and the amount of free cadmium there rises.

   too little — If little of the complex arrives, little cadmium enters the kidney cells, and their store hardly grows.

   observed in studies · Source 2

5. Cadmium in the cell → Binding to thiol groups Free cadmium binds to sulfhydryl groups (SH groups) of proteins. In this way it changes the shape and activity of these proteins. Enzymes with sulfur groups are then slowed. Source 5, 6↓ depletes Free cadmium occupies SH groups of proteins; the proteins change shape and activity, and enzymes with sulfur groups in their active site are slowed. observed in studies Source 5, 6
   ⚖ When the balance tips

   too much — If a lot of cadmium is bound, more enzymes are slowed; in studies reactive oxygen species in the cell increase, although cadmium itself does not form them.

   too little — If little cadmium is present, the SH groups of proteins remain mostly free for their tasks.

   observed in studies · Source 5

6. Binding to thiol groups → Zinc binding sites · Zinc Cadmium resembles zinc and occupies its places in enzymes and in zinc-finger proteins. The zinc bound there is released. Free zinc prompts the formation of metallothionein. Source 4, 6↓ depletes Cadmium displaces zinc from enzymes and from zinc-finger proteins that are involved in reading genes; with cadmium they work differently or no longer at all. observed in studies Source 4, 6
   ⚖ When the balance tips

   too much — If cadmium displaces a lot of zinc, more zinc is released in the cell; the free zinc prompts the formation of metallothionein.

   too little — If there is little zinc in the cell, more binding sites are free and cadmium finds room more easily; in animal models more cadmium is absorbed and stored when zinc is scarce.

   observed in studies · Source 4

7. Zinc binding sites → New metallothionein Zinc and cadmium prompt the cell to make more metallothionein. The new protein binds free cadmium ions tightly. Cadmium thus stays bound in storage for a long time. Source 3, 4↓ depletes Newly made metallothionein removes free cadmium from the cell and binds it tightly; zinc and cadmium themselves prompt its formation. observed in studies Source 3, 4
   ⚖ When the balance tips

   too much — If the cell makes a lot of metallothionein, free cadmium is quickly bound and stored; the store grows as a result, without free cadmium increasing.

   too little — If the cell makes little metallothionein, more cadmium stays free; in studies, animals without metallothionein respond more sensitively to cadmium.

   observed in studies · Source 3, 4

8. Binding to thiol groups → Glutathione complex · Glutathione Cadmium also binds to glutathione (GSH), the main thiol of the cell. Glutathione bound in this way is not available to the cell for other tasks. In studies peroxides are then broken down more slowly. Source 5↓ depletes Glutathione captures cadmium but is itself bound in the process; this glutathione is then no longer available for breaking down peroxides and other tasks. observed in studies Source 5
   ⚖ When the balance tips

   too much — If a lot of cadmium binds to glutathione, the free glutathione pool falls; in studies peroxides then persist longer.

   too little — If little glutathione is present, it can capture less cadmium, and more of it binds to proteins.

   observed in studies · Source 5

9. Glutathione complex → Excretion Cadmium stays bound in kidney and liver for a long time. It leaves the body only slowly, mainly with the urine. The store remains for decades. Source 2↓ depletes Cadmium leaves the body via the urine only in small amounts; the store in kidney and liver therefore remains for decades. established physiology Source 2
   ⚖ When the balance tips

   too much — If a lot of cadmium is stored in the kidney, the amount in the urine rises too; it follows the store over a long time.

   too little — If little is stored, only very little cadmium appears in the urine.

   established physiology · Source 2

Further stations

• Cadmium in food — also via inhaled air Cadmium reaches the gut with food and drinking water, and the lung with inhaled particles. More reaches the blood from the lung than from the gut. Source 2, 1↑ supplies Food, drinking water and inhaled particles supply cadmium; a larger share reaches the blood from the lung than from the gut. established physiology Source 2, 1
  ⚖ When the balance tips

  too much — If more cadmium arrives, it accumulates in liver and kidney over years, because it leaves the body only very slowly.

  too little — If little cadmium arrives, the store in liver and kidney hardly grows; what is already bound there remains for a long time.

  established physiology · Source 2

• Cadmium in the cell — released from the lysosome In the lysosome of the kidney cell, metallothionein is broken down. Cadmium ions are released and pass into the cytosol. New metallothionein binds them again. Source 2↓ depletes When the complex is broken down in the lysosome, cadmium is released; only this free cadmium acts on the cell's proteins, until new metallothionein binds it again. observed in studies Source 2
  ⚖ When the balance tips

  too much — If more cadmium is released than the cell can bind with new metallothionein, it stays free and occupies sulfur groups and zinc sites.

  too little — If little cadmium is released, the existing metallothionein quickly binds it again.

  observed in studies · Source 2, 3

Cofactors in this pathway

• Zinc — Cadmium occupies zinc binding sites; zinc prompts the formation of metallothionein; both compete for transporters Source 4, 3In the ORY catalogue as a laboratory value: Zink
• Glutathione — Binds cadmium via its SH group inside the cell and is then unavailable for other tasks Source 5In the ORY catalogue as a laboratory value: Glutathion (GSH)
• Iron — Cadmium uses DMT1, the uptake route for divalent iron; with little iron, more DMT1 is made Source 7, 1In the ORY catalogue as a laboratory value: Eisen
• Calcium — Cadmium can use calcium channels as an entry route into the cell Source 1, 6In the ORY catalogue as a laboratory value: Calcium (intrazellulär)
• Cysteine — Provides the SH groups with which metallothionein binds cadmium; cadmium thus stays tightly bound Source 2, 3

Sources

1. Thévenod F, Fels J et al. Channels, transporters and receptors for cadmium and cadmium complexes in eukaryotic cells: myths and facts. Biometals 2019 · PubMed 30701379
2. Sabolić I, Breljak D et al. Role of metallothionein in cadmium traffic and toxicity in kidneys and other mammalian organs. Biometals 2010 · PubMed 20549307
3. Klaassen CD, Liu J et al. Metallothionein protection of cadmium toxicity. Toxicol Appl Pharmacol 2009 · PubMed 19362100
4. Brzóska MM, Moniuszko-Jakoniuk J. Interactions between cadmium and zinc in the organism. Food Chem Toxicol 2001 · PubMed 11524135
5. Cuypers A, Plusquin M et al. Cadmium stress: an oxidative challenge. Biometals 2010 · PubMed 20361350
6. Bridges CC, Zalups RK. Molecular and ionic mimicry and the transport of toxic metals. Toxicol Appl Pharmacol 2005 · PubMed 15845419
7. Shawki A, Knight PB et al. H(+)-coupled divalent metal-ion transporter-1: functional properties, physiological roles and therapeutics. Curr Top Membr 2012 · PubMed 23177986

Related pathways

• Blei — Zink, Glutathion (GSH)
• Nickel — Zink, Glutathion (GSH)
• Quecksilber — Zink, Glutathion (GSH)

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