Transferrin: Definition, Biochemistry, Saturation and Pathologies Associated with Ferritin Levels

It is the protein that carries iron in the bloodstream.

It can bind them safely and circulates until it finds a cell with a transferrin receptor.

It binds to the receptor, enters the cell, delivers the iron, and then returns to the bloodstream. Transferrin is produced primarily in the liver and serves primarily to transfer iron from the duodenum , where it is absorbed, to cells that require it.

Ferritin is a protein that binds to iron and stores it safely intracellularly and releases it in a controlled manner. Ferritin is essential for the regulation of iron homeostasis, and reflects iron stores in the body and systemic inflammation.

Ferritin is found in most tissues as a cytosolic protein, but small amounts are secreted in the serum and function as an iron carrier.

Serum ferritin (SF) serves to store iron in a non-toxic form, to deposit it safely, and to transport iron to areas where it is needed.

Free iron is toxic to cells because it acts as a catalyst in the formation of free radicals from reactive oxygen species.


Transferrin consists of a single chain polypeptide of 679 amino acids, N-glucans, and two iron-binding sites. N-glucans show a complex structure and different transferrin glycoforms are named based on the total number of negatively charged terminal sialic acid residues.

Tetrasialotransferrin, which contains two biantennial N-glucans each terminated by a sialic acid, normally represents about 75-80% of the total transferrin in human serum.

Other common glycoforms are pentasialo, trisialo, hexasialo, and disialotransferrin, while asialo, monosialo, heptasialo, and octasialotransferrin are generally found in trace amounts or are not detectable at all.

There are also several homozygous and heterozygous B, C, and D genetic variants of transferrin, of which transferrin C is the most common phenotype.

Lack of iron

Iron deficiency is a decrease in total body iron that can be considered to have three successive stages of severity.

On average, an adult has storage iron stores corresponding to the amount of iron in a single unit of red blood cells (approximately 200 to 250 mg) in a woman and the amount of iron in three to four units in a man (about 750 to 1,000mg).

This storage iron is mobilized when iron requirements exceed iron supply.

Depletion of storage iron describes a decrease in iron with no effect on hemoglobin or on functional iron compounds in other tissues.

A further decrease in body iron produces iron deficiency without anemia, the stage in which a lack of iron limits the production of hemoglobin and other iron-requiring metabolites, but before the standards used to distinguish normal from anemic states detect the effect on the production of red blood cells.

Finally, further decreases in body iron produce frank iron deficiency anemia.

The serum iron test can reveal abnormally low or high blood iron levels. Your doctor will most likely order this test after another lab test shows an abnormal result.

Having too much iron, or not enough, can cause serious health problems. This test will help your doctor make a more accurate diagnosis.

Serum iron is measured in micrograms of iron per deciliter of blood (mcg / dL). The following are considered normal ranges for a serum iron test:

  • Hierro: 60 a 170 mcg / dL.
  • Transferrin saturation : 25 percent to 35 percent.
  • Total Iron Binding Capacity (TIBC): 240 to 450 mcg / dL

The normal amount of iron present in serum (bound to transferrin) is 11 to 32 µmol / L (60 to 178 µg / dL). Normal transferrin levels are 1.88 – 3.41 g / L (188 – 341 mg / dL).

In iron deficient states there is an increase in transferrin levels. The increase in transferrin levels and the fact that there is an iron deficiency means that the total percentage of transferrin that is actually bound to iron decreases.

So in these disease states there is a decrease in “transferrin saturation.” Another way of saying this is that there is an increase in “iron-binding capacity,” that is, transferrin waiting for iron to appear.

A transferrin saturation of <20% is indicative of iron deficiency, a transferrin saturation of> 50% indicates iron overload.

Abnormally high serum iron levels may mean that you have consumed too much iron, vitamin B-6, or vitamin B-12. High iron levels can indicate:

  • Hemolytic anemia or hemolysis – Your body does not have enough healthy red blood cells.
  • Liver conditions: such as liver necrosis (liver failure) and hepatitis.
  • Iron Poisoning – from consuming more than the recommended dose of iron supplements.
  • Iron overload – your body naturally retains too much iron

Abnormally low iron levels can mean that you haven’t consumed enough iron or that your body is not absorbing iron properly. Regularly having heavy menstrual periods can also lead to low iron levels.

Low iron levels can also indicate:

  • Anemia.
  • Pregnancy.
  • Gastrointestinal blood loss.
  • Some medications can affect the results of a serum iron test by increasing or decreasing your iron levels (birth control pills are commonly used and can affect iron levels).

Transferrin saturation

Ferritin levels taken in conjunction with serum iron and total iron-binding capacity (TIBC), SF is used as a diagnostic marker for iron deficiency anemia.

Transferrin saturation (TSAT) is the ratio of serum iron to TIBC. This value indicates how much serum iron is actually bound.

Furthermore, ferritin levels can be artificially high in cases of chronic disease where ferritin is elevated in its capacity as an acute-phase inflammatory protein and not as a marker of iron overload.

Therefore, ferritin is also used as a marker for iron overload disorders, such as hemochromatosis or hemosiderosis, hemophagocytic lymphohistiocytosis, and Still’s disease, in which ferritin levels may be abnormally elevated.

An important laboratory marker is the percentage of transferrin saturation. Because the body constantly absorbs more iron from food than it needs, there is a constant flow of iron in the blood.

Transferrin tries to keep up with this excess by rapidly binding and transporting iron to cells. As a result, the percentage of transferrin proteins that bind to iron increases as the available transferrin becomes more and more saturated with iron.

Combined with a measurement of serum iron (which is just iron bound to transferrin in the blood) the ‘total iron binding capacity’ or TIBC is obtained.

The TIBC can be used as a rough estimate of transferrin levels. Transferrin saturation can be calculated from these values.

TIBC = UIBC + serum iron (normal range 45-82 µmol / L or 251-460 µg / dL)

The% transferrin saturation »in a laboratory test is actually the answer to a mathematical equation. This value represents the percentage of how much iron is bound to the blood protein transferrin.

Transferrin saturation = (serum iron X 100) / TIBC

Transferrin Saturation (TS%) is a common laboratory test that can give us an idea of ​​the diagnosis of hemochromatosis and the state of iron overload in our bodies.

Pathologies associated with ferritin levels

Ferritin levels are associated with metabolic syndrome in children and adolescents.

In adults, ferritin levels are independently associated with a high prevalence of dyslipidemia, nonalcoholic fatty liver disease, insulin resistance, and stroke.

Furthermore, some studies have suggested that it also has a role in the development of central obesity, hypertension, type 2 diabetes mellitus, and coronary artery disease.

Therefore, establishing hematological reference values, including those for ferritin, is essential to assess the individual risk of these diseases.

Alcohol appears to inhibit the glycosylation of several glycoproteins, including transferrin, and in subjects who consume excessive amounts of alcohol, plasma transferrin often lacks up to four of these sialic acid residues.

This results in asialo and disialotransferrins, which are now collectively referred to as carbohydrate-deficient transferrin.

Consumption of more than 80 g of alcohol / day leads to an increase in the plasma concentration of carbohydrate-deficient transferrin, regardless of any underlying liver disease.

This returns to normal concentrations within two weeks of abstinence.

The measurement of carbohydrate-deficient transferrin has been proposed as a marker of excessive alcohol consumption, although it is not widely used; sensitivity is approximately 80% and specificity somewhat higher, but results do not reflect the nature or severity of any liver disease