Ferritin

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Ferritin
Ferritin
Surface model of mouse ferritin (a single subunit is highlighted in purple) according to PDB  1LB3

Existing structural data : 1fha , 2cei , 2chi , 2cih , clu , cn6 , cn7 , 2fha , 2iu2

Mass / length primary structure 174/182 amino acids (L / H)
Secondary to quaternary structure 24-mer
Isoforms L / H
Enzyme classification
EC, category 1.16.3.1 ,  oxidoreductase
Response type oxidation
Substrate 4 Fe 2+ + 4 H + + O 2
Products 4 Fe 3+ + 2 H 2 O
Occurrence
Parent taxon Creature

Ferritin (FT) ( Latin: ferrum , 'iron'), also depot iron , is a protein complex that occurs in animals, plants and bacteria, where it serves as a storage substance for iron . In humans, ferritin is mainly found in the liver , spleen and bone marrow . In healthy people, around 20% of all iron is stored in ferritin. Mutations in the genes that code for ferritin subunits can cause hereditary metabolic disorders (see table in the text).

Although most of the ferritin is inside the cells, the ferritin concentration in human blood serum is a meaningful measure of the organism's total iron store. The determination of ferritin is now routine in the laboratory diagnosis and has especially in the diagnosis of anemia and hemochromatosis a high priority. When interpreting, however, it should be noted that the value can be increased by the acute phase reaction and thus an apparent disease is diagnosed. At the same time, an iron deficiency that may actually be present can be concealed.

Structure and occurrence

Ferritins are about 8 nanometers in size, filled with iron hydroxide oxide, disc-shaped proteins that are made up of 24 protein subunits (see picture). The subunits are about 150 to 160 amino acids in length in bacterioferritin , 170 to 180 amino acids in animal ferritin and up to over 200 amino acids in vegetable ferritin. The protein shell without iron atoms in the core is called apoferritin and has a mass of 400 kDa. Together with around 4500 iron atoms, a ferritin complex in humans has a mass of around 900  kDa .

Plant apoferritin is found in two isoforms in chloroplasts . The human ferritin consists of two different sub-units, the L (light) chain and the H (heavy) chain. The heavy chain contains an iron binding site, which also has a ferrooxidase center to oxidize iron to III +. The light chain has no enzymatic activity, but is responsible for transporting the iron atoms into the nucleus. The composition of ferritin differs depending on the organ. The ferritin in the heart and brain has significantly more H-ferritin, whereas in the spleen and liver the L-ferritin predominates, since there the iron storage function predominates.

Gene name (HGNC) Gene locus Length ( AA ) UniProt OMIM pathology
FTL 19q13.3-13.4 174 P02792 134790 Hyperferritinemia cataract syndrome ; Neuroferritinopathy
FTH 11q12-q13 182 P02794 134770 Iron overload, autosomal dominant
FTMT 5q21.3 193 Q8N4E7 608847

Biosynthesis and Biological Function

Iron ions in the cytosol bind to latent mRNA molecules that are present there , which code for FTL (light chain) or FTH (heavy chain), and cause their activation and binding to ribosomes with subsequent translation . When the iron level drops, a certain aconitase loses its [4Fe-4S] cluster, subsequently acts as an iron regulatory protein (IRP) and inhibits ferritin translation by binding to iron-responsive elements (IRE) in the ferritin mRNA.

The tasks of ferritin are to oxidize iron (II), transport iron (III) into the interior of the molecule, build up the iron mineral inside and mobilize this iron if necessary.

To fill the ferritin cavity with iron, poly (rC) binding protein-1 (PCBP1) is required as a chaperone .

Mitochondrial ferritin ( FTMT ) can serve as additional iron store in mitochondria during pathological conditions. Besides ferritin, hemoglobin and hemosiderin are the most important storage forms of iron in the organism (proportion approx. 50 and 30%, respectively).

Laboratory diagnostics

Reference range

The following reference values ​​apply to ferritin for humans:

Baby:

  • Umbilical cord blood 30-276 ng / ml
  • 2-3 Week 90-628 ng / ml
  • 1st month 144-399 ng / ml
  • 2nd month 87-430 ng / ml
  • 4th month 37-223 ng / ml

Children:

  • 6 months-15. Age 7-142 ng / ml

Women:

  • 16.-50. Age 22-112 ng / ml
  • 65th-90th Age 13-651 ng / ml

Men:

  • 16.-50. Age 34-310 ng / ml
  • 65-87 Age 4-665 ng / ml

Ferritin level too low

Ferritin level too high

See also

Individual evidence

  1. ^ Richard J. Epstein: Human Molecular Biology: An Introduction to the Molecular Basis of Health and Disease. Cambridge University Press, 2003, ISBN 0-521-64481-X , p. 161.
  2. ^ Andrzej Friedman, Paolo Arosio, Dario Finazzi, Dariusz Koziorowski, Jolanta Galazka-Friedman: Ferritin as an important player in neurodegeneration . In: Parkinsonism & Related Disorders . tape 17 , no. 6 , July 2011, ISSN  1353-8020 , p. 423-430 , doi : 10.1016 / j.parkreldis.2011.03.016 ( elsevier.com [accessed May 3, 2018]).
  3. ↑ ferritin.  In: Online Mendelian Inheritance in Man . (English).
  4. ↑ H. Shi et al: A cytosolic iron chaperone that delivers iron to ferritin. In: Science . 320, 5880, 2008, pp. 1207-1210. PMID 18511687 .
  5. ↑ PM Harrison, P. Arosio: The ferritin: molecular properties, iron storage function and cellular regulation. In: Biochim Biophys Acta . 31, 1275, 1996, pp. 161-203. PMID 8695634 .
  6. ↑ ferritin.  In: Online Mendelian Inheritance in Man . (English).
  7. ↑ Labor Lexicon .

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