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Iron normally enters the body through the gastrointestinal tract, mostly through the
enterocytes of the duodenum. The absorption of inorganic iron begins with reduction of iron to
its ferrous form by a ferrireductase and its subsequent transport across the enterocyte apical
membrane by a divalent iron transporter, DMT-1. Once inside the enterocyte, iron is transferred
across the basolateral membrane into the circulation by ferroportin and hephaestin. Once ferric
iron enters the plasma, it is bound by transferrin, which, after forming a complex with the
transferrin receptor, transports iron into cells. This transport compartment or iron carried by
transferrin is the smallest, amounting to only 2-3 mg, but it is the most active of the iron
compartments, with turnover rates of at least 10 times a day
.
Each iron atom cycles repeatedly from plasma and extracellular fluid to the marrow,
where it is incorporated into hemoglobin.Hemoglobin is the biggest iron compartment in the
body, containing approximately 1.5-2 g of body iron. Iron circulates in the blood within
erythrocytes for about 4 months. It then travels to phagocytes where senescent erythrocytes
are engulfed, hemoglobin is digested, and iron is released to plasma, where the cycle
continues. With each cycle, a proportion of iron is transferred to storage sites and incorporated
into ferritin or hemosiderin. Ferritin, the main storage form of iron, is found in virtually all cells of
the body and also in tissue fluids. The size of the iron storage compartment is quite variable,
about ~1g. Smaller amounts of iron are also present in myoglobin and in many other enzymes.
Williams
harpers
In addition, approximately 10% of newly formed erythrocytes are destroyed within the marrow
and its iron released, bypassing the circulating blood part of the cycle (ineffective
erythropoiesis). The numbers indicate the approximate amount of iron (in mg) in various
compartments and fluxes of iron (mg/day) that enter and leave each of these iron compartments
in healthy adults who do not have bleeding or ther blood disorders.
The size of the iron storage compartment is quite variable. Normally, in adult men, it amounts to 800 to 2000 mg; in
adult women, it is a few hundred milligrams.
STORAGE COMPARTMENT
Iron is stored either as ferritin or as hemosiderin. The former is
water-soluble; the latter is water-insoluble. The protein ferritin is composed
of 24 similar or identical subunits arranged as 12 dimers forming
a dodecahedron that approximates a hollow sphere with a cavity capable
of storing up to 4500 Fe atoms as hydrous ferric oxide polymers.1,2
The ferritin subunits are of H (heavy) or L (light) type. H subunits have
ferroxidase activity, thereby enabling ferritin to take up or release iron
quite rapidly. Ferritin that is rich in H subunits takes up iron more readily,
but retains it less avidly than does ferritin composed predominantly
of L subunits. Much of the storage iron in liver and spleen is in ferritin
containing mostly L subunits.
Ferritin is found in virtually all cells of the body and also in tissue
fluids. In plasma ferritin is present in minute concentrations. The size of the iron storage compartment is quite
variable. Normally, in adult men, it amounts to 800 to 2000 mg; in adult women,
it is a few hundred milligrams. The mobilization of storage iron from
ferritin involves the reduction of Fe3+ to Fe2+, its release from the core
crystal and its diffusion out of the apoferritin shell. As it passes from
cytosol to plasma, it must be reoxidized to Fe3+, either by hephaestin
or ceruloplasmin in the cell membrane or by ceruloplasmin in plasma,
before it binds to transferrin. Alternatively, iron may be released from
ferritin by autophagy followed by lysosomal degradation.3
ALL ABOUT HEPCIDIN CHURVA
Systemic iron homeostasis is maintained by the hepatic peptide hormone
hepcidin, which regulates plasma iron concentrations, the absorption of dietary iron, and the release of
iron from macrophages involved in iron recycling and storage and from hepatocytes that store iron.
The cellular iron exporter ferroportin serves as the receptor for hepcidin and is destroyed when
the complex is formed. This impairs transport from intestinal mucosal cells,
from macrophages and from hepatocytes into the plasma, and lowers iron
absorption and release from stores.
Hepcidin decreases plasma iron levels by causing iron to be sequestered within cells, predominantly in
macrophages or enterocytes, the latter of which are then shed along with their absorbed iron.