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From Proteopedia

Revision as of 15:38, 26 January 2017

Transferrin (or siderophilin) is a beta-globulin protein of 76 kDa molecular weight, synthesized by the liver ^[1]. Human transferrin is encoded by the TF gene ^[2]. It consists of a single polypeptide chain carrying two iron uptake sites, at the rate of 2 iron atoms per transfer molecule. The transferrin function is the transport of iron from the intestine to hepatic reserves and reticulocytes. The affinity of transferrin for Fe(III) is extremely high (association constant is 1020 M−1 at pH 7.4) but decreases progressively with decreasing pH ^[3]. So transferrins are iron-binding blood plasma glycoproteins that control the level of free iron (Fe) in biological fluids in link with the pH ^[4]. When not bound to iron, transferrin is known as "apotransferrin".

Structure

Disease

Transferrin can be implicated in diseases directly or not such as congenital atransferrinemia (also called familial hypotransferrinemia) or Hemochromatosis type 3.

Atransferrinemia: Atransferrinemia is a rare hereditary metabolic disorder which a frequency of 1/1 000 000. It is an autosomal recessive disease caused by a mutation of TF gene.

This disease is a deficiency to transferrin which cause a lack of iron in the medullary precursors of red blood cells, an accumulation of iron in the peripheric tissue in the liver, heart, pancreas, thyroid, kidney and bone joints and a diminution of red blood cell synthesis. It can cause death by heart failure or infection (pneumonia).

Atransferrinemia has a lot of different symptom which are mainly: Growth retardation, infections prevalence, anaemia, heart failure, hepatics insufficiency, arthropathy and hypothyroidy. Moreover, other symptoms can be detected with an adult. Indeed, it can cause chronic alcoholism, neurosis, and GRACILE syndrome. However, other diagnostics method must confirm the disease, it can be a prenatal diagnostic which is a research of mutation for the parents, or molecular genetic testing to detect the mutation of TF, or a dosage of transferrin to detect anaemia (if there are less of 35mg/dL, the patient is sick).

A mutation of TF gene which code for the transferrin causes this disease. This mutation could be a substitution mutation on the 77 or 477 positions which replace respectively Aspartic acid Asparagine and Arginine by proline.

Today, Atransferrinemia is not curable and the treatments have good prognostic but the consequence for long term are unknow. A monthly injection of plasma or apotransferrin can decrease the overage of irons with a substitution of TF, those injections are for lifetime.

Hemochromatosis type 3: Hemochromatosis type 3 is another rare disease cause by failure of the transferrin receptor 2. A mutation on the chromosome 7 cause a lack of receptor and an accumulation of iron on liver and heart. Dosage of transferrin detects it; a saturation is consequence of hemochromatosis type 3.

Structural highlights

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Interactions

Interaction with insulin-like growth factor: In the circulation, most of the insulin-like growth factors (IGFs) are bound to a ternary 150 kDa complex with IGF-binding protein (IGFBP)-3 and the acid labile subunit. Transferrin (Tf) is a component of a major IGF-binding fraction separated from human plasma and Tf binds to IGFs specifically. The data suggest that Tf may play an important role in regulating IGF/IGFBP-3 functions,^[5].

References

1. ↑ Aisen, P., Leibman, A., & Zweier, J. L. (1978). Stoichiometric and site characteristics of the binding of iron to human transferrin. Journal of Biological Chemistry, 253(6), 1930-1937.
2. ↑ Yang, F., Lum, J. B., McGill, J. R., Moore, C. M., Naylor, S. L., Van Bragt, P. H., ... & Bowman, B. H. (1984). Human transferrin: cDNA characterization and chromosomal localization. Proceedings of the National Academy of Sciences, 81(9), 2752-2756.
3. ↑ Aisen, P., Leibman, A., & Zweier, J. L. (1978). Stoichiometric and site characteristics of the binding of iron to human transferrin. Journal of Biological Chemistry, 253(6), 1930-1937.
4. ↑ : CRICHTON, R. R., & CHARLOTEAUX‐WAUTERS, M. (1987). Iron transport and storage. European Journal of Biochemistry, 164(3), 485-506.
5. ↑ Storch, S., Kübler, B., Höning, S., Ackmann, M., Zapf, J., Blum, W., & Braulke, T. (2001). Transferrin binds insulin‐like growth factors and affects binding properties of insulin‐like growth factor binding protein‐3. FEBS letters, 509(3), 395-398