Transferrin is the major iron transport protein (transports iron through blood). Fe3+ is the form of iron that binds to transferrin, so the Fe2+ transported through ferroportin must be oxidized to Fe3+. There are 2 copper-containing proteins that catalyze this oxidation of Fe2+: hephaestin and ceruloplasmin. Hephaestin is found in the membrane of enterocytes, while ceruloplasmin is the major copper transport protein in blood. Hephaestin is the primary protein that performs this function in a coupled manner (need to occur together) with transport through ferroportin. This means that the Fe2+ needs to be oxidized to be transported through ferroportin. Evidence suggests that ceruloplasmin is involved in oxidizing Fe2+ when iron status is low¹. Once oxidized, Fe3+ binds to transferrin and is transported to a tissue cell that contains a transferrin receptor. Transferrin binds to the transferrin receptor and is endocytosed, as shown below².

Figure 12.721 Transport and uptake of iron

Once inside cells, the iron can be used for cellular purposes (cofactor for enzyme etc.) or it can be stored in the iron storage proteins ferritin or hemosiderin. Ferritin is the primary iron storage protein, but at higher concentrations, iron is also stored in hemosiderin².

Figure 12.722 Fates of iron within cells

There are 3 major compartments of iron in the body³:

1. Functional Iron

2. Storage Iron

3. Transport Iron

Functional iron consists of iron performing some function. There are 3 functional iron subcompartments.

1. Hemoglobin

2. Myoglobin

3. Iron-containing enzymes

The functions of these subcompartments are discussed in the next section.

Iron Stores consist of:

1. Ferritin

2. Hemosiderin

The liver is the primary storage site in the body, with the spleen and bone marrow being the other major storage sites.

Circulating iron is found in transferrin³.

The following table shows how much iron is distributed among the different compartments.

Table 12.721 Iron Distribution in adults (mg Fe/kg body weight)³

Hopefully you notice that the majority of iron is in the functional iron compartment. The figure below further reinforces this point, showing that most iron is found in red blood cells (hemoglobin) and tissues (myoglobin).

Figure 12.723 Iron distribution in different compartments⁴

Also notice how small oral intake and excretion are compared to the amount found in the different compartments in the body. As a result, iron recycling is really important, because red blood cells only live for 120 days. Red blood cells are broken down in the liver, spleen, and bone marrow and the iron can be used for the same purposes as described earlier: cellular use, storage, or transported to another tissue on transferrin². Most of this iron will be used for heme and ultimately red blood cell synthesis. The figure below summarizes the potential uses of iron recycled from red blood cells.

Figure 12.724 Iron recycling from red blood cells

Iron is unique among minerals in that our body has limited excretion ability. Thus, absorption is controlled by the hormone hepcidin. The liver has an iron sensor so when iron levels get high, this sensor signals for the release of hepcidin. Hepcidin causes degradation of ferroportin. Thus, the iron is not able to be transported into circulation⁵.

Figure 12.725 Action of hepcidin⁴

The iron is now trapped in the enterocyte, which is eventually sloughed off and excreted in feces. Thus, iron absorption is decreased through the action of hepcidin.

Figure 12.726  Enterocytes are sloughed off the villus and unless digested and their components reabsorbed, they will be excreted in feces

References & Links

1. Yehuda S, Mostofsky DI (2010) Iron Deficiency and Overload: From Basic Biology to Clinical Medicine. New York, NY. Humana Press.

2. Gropper SS, Smith JL, Groff JL. (2008) Advanced nutrition and human metabolism. Belmont, CA: Wadsworth Publishing.

3. Stipanuk MH. (2006) Biochemical, physiological, & molecular aspects of human nutrition. St. Louis, MO: Saunders Elsevier.

4. http://en.wikipedia.org/wiki/File:Iron_metabolism.svg

5. Nemeth E, Ganz T. (2006) Regulation of iron metabolism by hepcidin. Annu Rev Nutr 26: 323-342.