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Depositi di ferro (nella ferritina):
Uomo 1000 mg
Donna 200-400 mg
Transferrins are iron-binding blood plasma glycoproteins that
control the level of free iron in biological fluids.
Transferrin glycoproteins bind iron very tightly, but reversibly.
Although iron bound to transferrin is less than 0.1% (4 mg) of the
total body iron, it is the most important iron pool, with the highest
rate of turnover (25 mg/24 h). Transferrin has a molecular weight
of around 80 kDa and contains two specific high-affinity Fe(III)
binding sites. The affinity of transferrin for Fe(III) is extremely high
at pH 7.4 but decreases progressively with decreasing pH below
When not bound to iron, it is known as "apotransferrin" .
In humans, transferrin consists of a polypeptide chain containing 679
amino acids. The protein is composed of alpha helices and beta sheets
to form two domains. The N- and C- terminal sequences are
represented by globular lobes and between the two lobes is an ironbinding site.
When a transferrin protein loaded with iron encounters
a transferrin receptor on the surface of a cell (e.g., to
erythroid precursors in the bone marrow), it binds to it
and, as a consequence, is transported into the cell in a
vesicle by receptor-mediated endocytosis. The pH of
the vesicle is reduced by hydrogen ion pumps (H+
ATPases) to about 5.5, causing transferrin to release its
iron ions. The receptor (with its ligand, transferrin,
bound) is then transported through the endocytic cycle
back to the cell surface, ready for another round of iron
uptake. Each transferrin molecule has the ability to
carry two iron ions in the ferric form (Fe3+).
Ferritins are complex twenty-four subunit heteropolymers of H (for
heavy) and L (for light) protein subunits.
The subunits of the ferritin molecule form a sphere with a central
cavity in which up to 4500 atoms of crystalline iron are stored.
The ranges for ferritin can vary between laboratories
but are usually between 30–400 ng/mL (=μg/L) for
males, and 15–200 ng/mL (=μg/L) for females.
Serum Iron (SI):
Men: 65 to 176 μg/dL
Women: 50 to 170 μg/dL
TIBC (total iron binding capacity) : 240–450 μg/dL
Transferrin saturation: 20–50%
μg/dL = micrograms per deciliter
Normal reference ranges for transferrin are 204–360
Iron in food is present as ferric iron or as heme.
Currently, there are two prevailing hypotheses explaining
the mechanisms of iron uptake by enterocytes; first, heme
is taken up by receptor mediated endocytosis; secondly,
the recent discovery of a heme transporter (PCFT/HCP1)
that may have the capability of transferring heme from
the small intestinal lumen directly into the cytoplasm
Non-haem iron requires to be converted in ferrous iron
by the apical ferric reductase duodenal cytochrome B
although the physiological significance of this pathway
is the subject of continued debate. Following the
reduction, iron crosses into the cytoplasm via an apical
iron transporter, DMT1, divalent metal transporter 1.
Specialised mechanism for exporting iron to plasma: the
iron exporter ferroportin.
Ferroportin needs copper-ferroxidases to release iron to
plasma transferrin, namely hephaestin in duodenal cells
and ceruloplasmin in hepatocytes, and macrophages
The 25-amino acid peptide of hepcidin is secreted by the
liver, which seems to be the "master regulator" of iron
Hepcidin inhibits iron transport by binding to the iron
channel ferroportin, which is located on the basolateral
surface of gut enterocytes and the plasma membrane of
reticuloendothelial cells (macrophages).
By inhibiting ferroportin, hepcidin prevents enterocytes of
the intestines from secreting iron into the hepatic portal
system, thereby functionally reducing iron absorption.
The liver peptide hepcidin regulates intestinal iron absorption and
iron release from storage cells by binding ferroportin causing its
internalization and degradation, thus exerting a general inhibitory
effect on iron release in the body.
Animal models clarified the role of hepcidin as hepcidin knock-out
mice developed massive iron overload and hepcidin overexpression induced iron deficiency.
In physiological conditions, hepcidin production is tightly regulated
in response to signals released from other organs, prevalently from
bone marrow (erythroid regulator) and the iron stores (store
regulator). Hepcidin levels increase in iron overload in order to limit
iron absorption and are reduced up to undetectable levels in iron
deficient erythropoiesis, either dependent from decreased iron
supply or increased erythroid iron requirement, to allow iron
Ferroportin acts under the control of hepcidin and this
interaction can explain the systemic regulation of iron
metabolism. Interestingly, it has been shown that
hepcidin-induced internalization of ferroportin
requires binding and cooperative interaction with
Janus kinase (Jak2). Hepcidin binding to ferroportin
results in the phosphorylation of ferroportin, a step
necessary for its internalization by clathrin-coated pits
and the kinase responsible for the phosphorylation is
Studies on genetic disorders of iron metabolism
and of corresponding animal models have
identified the hemochromatosis proteins (HFE,
TFR2 and HJV) as the iron-dependent regulators of
hepcidin expression. Patients affected by
hemochromatosis have a defective synthesis of
hepcidin that is absent in JH, reduced in type 3 HH
due to TFR2 mutation or inadequate to the
amount of iron overload in classical HH.
L'emocromatosi (greco hàima sangue, e chroma, -atos
colore), in passato chiamato anche diabete bronzino, è
una malattia metabolica genetica dovuta all'accumulo di
notevoli quantità di ferro in diversi organi e tessuti quali:
fegato, pancreas, cute, cuore ed alcune ghiandole
L'assorbimento intestinale del ferro negli alimenti è
aumentato. Ciò è causato, nella maggior parte dei casi,
dalla mutazione genetica del gene HFE, localizzato sul
cromosoma 6
Unusually, the official gene symbol (HFE for High Iron Fe)
is not an abbreviation of the official name
Tra le popolazioni nord-europee il tasso di eterozigosi è
del 10% circa, con lo 0,3-0,5% di omozigosi. Le
manifestazioni sono 5-10 volte più frequente negli
uomini, in quanto l'espressione genica della malattia è
influenzata da fattori esterni quali l'introito di ferro con la
dieta, le perdite ematiche associate a mestruazioni e
gravidanza, le donazioni di sangue. L'esordio avviene
comunemente tra i 40 ed i 60 anni; i soggetti più giovani
possono essere identificati tramite screening.
Hemojuvelin (HJV/RGMc/HFE2) is a membranebound and soluble protein in mammals that is
responsible for the iron overload condition known as
juvenile hemochromatosis in humans, a severe form
of hemochromatosis. In humans, the hemojuvelin
protein is encoded by the HFE2 gene.