Transferrin und Transferrinsättigung (TFS): the pathway in the body

Transferrin und Transferrinsättigung (TFS) is part of the pathway “Iron and ferritin”. This page shows the whole pathway; the station of Transferrin und Transferrinsättigung (TFS) is highlighted.

Where this laboratory value sits: Transferrin iron — Fe³⁺ in blood. Ferroportin is the only known door through which iron leaves a cell. Hephaestin oxidises it back to Fe³⁺ on the way; in the blood it binds to transferrin. Transferrin keeps it dissolved and unreactive. Source 1, 2

In brief

Iron is a trace element that the body stores in the protein ferritin and distributes in the blood bound to transferrin. In the haem of haemoglobin it binds oxygen, and in many enzymes it transfers electrons. Via hepcidin, the liver controls how much iron the gut releases.

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. Iron in food → Fe²⁺ in the gut Dcytb · Vitamin C The enzyme Dcytb sits on the surface of the gut cell. It donates an electron and turns Fe³⁺ into ferrous Fe²⁺; vitamin C supplies the electrons for this. Only as Fe²⁺ does iron fit through the transporter DMT1. Source 5, 1↑ supplies Only as Fe²⁺ does iron fit through the transporter DMT1. Dcytb and vitamin C thus make dietary Fe³⁺ absorbable in the first place; haem iron does not depend on this step. established physiology Source 5, 1
   ⚖ When the balance tips

   too much — If the gut cell is well loaded with iron, it makes less Dcytb and DMT1; it thus lets in less new iron.

   too little — If there is little iron in the body, the gut cell makes more Dcytb and DMT1, controlled by the oxygen sensor HIF-2α; more Fe³⁺ is thus converted and absorbed.

   established physiology · Source 5, 1

2. Fe²⁺ in the gut → Iron in the gut cell DMT1 The transporter DMT1 moves Fe²⁺ into the cell. There it is either stored in ferritin or passed on into the blood. Hepcidin decides where it goes. Source 1↕ both, depending on amount This is where the decision is made: if ferroportin sits in the membrane, the iron goes into the blood; if hepcidin has had it broken down, the iron stays in ferritin and is lost with the shed cell. established physiology Source 1, 2
   ⚖ When the balance tips

   too much — If iron builds up in the gut cell because a lot of hepcidin has ferroportin broken down, it is bound in ferritin and leaves the body with the cell when it is shed after a few days.

   too little — If little hepcidin is present, a lot of ferroportin stays in the membrane, and the gut cell passes most of its iron on into the blood instead of storing it in ferritin.

   established physiology · Source 1, 2

3. Iron in the gut cell → Transferrin iron Ferroportin · Hephaestin (copper) Ferroportin is the only known door through which iron leaves a cell. Hephaestin oxidises it back to Fe³⁺ on the way; in the blood it binds to transferrin. Transferrin keeps it dissolved and unreactive. Source 1, 2↑ supplies Transferrin keeps iron in the blood dissolved and unreactive and delivers it to cells, above all to the bone marrow for making red blood cells. Most of this iron comes from macrophages that break down old red blood cells. established physiology Source 2, 1
   ⚖ When the balance tips

   too much — If transferrin is largely saturated with iron, iron that is not bound to transferrin appears in the blood; the liver, heart and gland cells absorb it in an unregulated way and store it.

   too little — If little iron is bound to transferrin, less reaches the bone marrow; because it uses most of the iron in the blood, it then makes less haemoglobin.

   established physiology · Source 2

4. Iron in the cell → Ferritin Ferroxidase (H chain) Ferritin is a hollow sphere made of 24 subunits. Its H chains oxidise Fe²⁺ and deposit it as a mineral inside – this keeps the iron safely stored. When needed, the cell releases the iron again via ferritinophagy. Source 3↕ both, depending on amount Ferritin absorbs free iron and keeps it unreactive, but releases it again when needed: via NCOA4 it is broken down in lysosomes (ferritinophagy). It thus buffers the cell's iron status in both directions. established physiology Source 3
   ⚖ When the balance tips

   too much — If a lot of iron enters the cell, the IRPs detach from the messenger RNA and more ferritin is made to absorb the excess; if its capacity is not enough, more free iron is left over.

   too little — If there is little iron in the cell, ferritin is broken down in lysosomes via NCOA4 and the stored iron is released again; at the same time the cell makes less new ferritin.

   established physiology · Source 3, 6

5. Ferritin → Ferritin in blood A small part of the ferritin passes from cells into the blood. This form is largely iron-free and is the one measured in the laboratory. Its role in the blood is unclear; inflammation also raises it independently of iron. Source 3, 2↑ supplies What role ferritin plays in the blood is unclear; iron transport to particular tissues is discussed. Its amount follows the ferritin in the cells and also rises with inflammation independently of it. contested Source 3, 2
   ⚖ When the balance tips

   too much — If there is a lot of iron in the stores, the cells make more ferritin, and it also rises in the blood; inflammation raises it independently of this.

   too little — If the iron stores are almost empty, hardly any ferritin is made, and there is little of it in the blood too; this happens before less haemoglobin is made.

   established physiology · Source 2, 3

6. Iron in the cell → Haem Ferrochelatase · Protoporphyrin IX In the mitochondrion, ferrochelatase inserts Fe²⁺ into the protoporphyrin IX ring. This forms haem, the red pigment that binds oxygen. When little iron is available, the enzyme inserts zinc instead. Source 4↑ supplies Haem is the form in which iron works: in haemoglobin it binds oxygen, in the cytochromes of the respiratory chain it transfers electrons. Free haem inhibits ALA synthase and so slows its own formation. established physiology Source 4
   ⚖ When the balance tips

   too much — If haem builds up, it slows ALA synthase and less new haem is made; excess haem is broken down by haem oxygenase into biliverdin, iron and carbon monoxide.

   too little — If there is little iron in the mitochondria, ferrochelatase inserts zinc instead of iron into protoporphyrin IX; zinc protoporphyrin forms instead of haem.

   established physiology · Source 4, 2

7. Haem → Haemoglobin · Globin chains Four haem groups and four globin chains form haemoglobin. Most of the body's iron is found in this molecule. When little iron is available, less of it is made. Source 4, 1↑ supplies Haemoglobin picks up oxygen in the lungs and releases it in the tissues. Macrophages break down old red blood cells and return the iron to the blood; most of the iron is thus used again and again. established physiology Source 1, 2
   ⚖ When the balance tips

   too much — Haemoglobin holds only as much iron as haem is made; more iron does not increase it. Excess iron goes into the stores of the liver and macrophages.

   too little — If little iron is available, less haemoglobin is made; the red blood cells turn out smaller and paler, and the blood carries less oxygen.

   established physiology · Source 2, 1

Further stations

• Iron in food — Fe³⁺ and haem iron Plant foods mostly contain iron as ferric Fe³⁺. In meat it is present as haem iron, which the gut cell absorbs by a separate route. There is no regulated route for excreting iron. Source 1↑ supplies Dietary iron is the only source from which the body replaces losses; there is no regulated route of excretion. The body therefore controls its iron stock solely through absorption in the gut. established physiology Source 1, 2
  ⚖ When the balance tips

  too much — If more iron arrives than the body needs, there is no regulated way out; the stock is held only because the liver makes more hepcidin and the gut absorbs less.

  too little — If little iron arrives, hepcidin falls; more ferroportin stays in the membrane of the gut cell, and the gut absorbs a larger share of the iron on offer.

  established physiology · Source 1, 2

• Iron in the cell — via the transferrin receptor Cells bind loaded transferrin at the receptor TfR1 and bring it inside. In the acidic vesicle the iron is released, and STEAP3 turns it back into Fe²⁺. When the cell holds little iron, it makes more receptors. Source 6↑ supplies The released Fe²⁺ forms a small, mobile pool, the labile iron pool. Mitochondria draw iron from it for haem and iron–sulphur clusters; via the proteins IRP1 and IRP2 it reports the cell's iron status. established physiology Source 6
  ⚖ When the balance tips

  too much — If free Fe²⁺ builds up in the cell, the Fenton reaction turns hydrogen peroxide into reactive hydroxyl radicals; they alter membrane fats, in cell culture up to iron-dependent cell death (ferroptosis).

  too little — If there is little iron in the cell, the IRPs bind to the messenger RNA: more TfR1 receptors form to draw in more iron, and less ferritin that would lock it away.

  observed in studies · Source 6

Cofactors in this pathway

• Vitamin C — Supplies Dcytb with the electrons that turn Fe³⁺ into Fe²⁺ in the gut; with little of it, less Fe³⁺ is converted Source 5In the ORY catalogue as a laboratory value: Vitamin C (Ascorbinsäure)
• Copper — Metal of the ferroxidase hephaestin, which oxidises iron to Fe³⁺ as it enters the blood; otherwise release stalls Source 1, 2In the ORY catalogue as a laboratory value: Kupfer (Cu)
• Vitamin B6 — Cofactor of ALA synthase, the first enzyme of haem synthesis; with little PLP, less haem forms Source 4In the ORY catalogue as a laboratory value: Vitamin B6
• Glycine — Building block from which ALA synthase forms the haem precursor ALA with succinyl-CoA; without glycine no ALA Source 4In the ORY catalogue as a laboratory value: Glycin
• Zinc — Metal of ALA dehydratase, the second enzyme of haem synthesis; also inserted into protoporphyrin when iron is scarce Source 4In the ORY catalogue as a laboratory value: Zink

What acts on this pathway

• Hepcidin — Hepcidin is a hormone made by the liver. It binds to ferroportin and causes it to be broken down; the gut cell then releases less iron into the blood. Higher hepcidin levels in the blood have been described during inflammation. Source 2

Sources

1. Anderson GJ, Frazer DM. Current understanding of iron homeostasis. Am J Clin Nutr 2017 · PubMed 29070551
2. Ganz T. Systemic iron homeostasis. Physiol Rev 2013 · PubMed 24137020
3. Plays M, Müller S, Rodriguez R. Chemistry and biology of ferritin. Metallomics 2021 · PubMed 33881539
4. Ajioka RS, Phillips JD, Kushner JP. Biosynthesis of heme in mammals. Biochim Biophys Acta 2006 · PubMed 16839620
5. McKie AT. The role of Dcytb in iron metabolism: an update. Biochem Soc Trans 2008 · PubMed 19021532
6. Gao G, Li J, Zhang Y et al. Cellular Iron Metabolism and Regulation. Adv Exp Med Biol 2019 · PubMed 31456203

Whole pathway: Iron and ferritin

Related pathways

• Blood formation and bilirubin — haem
• HbA1c and insulin — haemoglobin
• 8-OHdG — Vitamin C (Ascorbinsäure), Kupfer (Cu)
• Dopamine, noradrenaline, adrenaline — Vitamin C (Ascorbinsäure), Kupfer (Cu)
• Antioxidant capacity — Vitamin C (Ascorbinsäure), Zink

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