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8

Uptake, transport and storage of iron

Iron, when taken up with the food and processed in the mouth (chewing, admixture of saliva) is
3+
3+
mostly present in its ferric (Fe ) form and thus gets into the gastro-intestinal tract as Fe . In
2+
case of an intact milieu in the small intestines, ferric iron is reduced to its ferrous form (Fe ).
Only in this oxidation state can iron be absorbed by the epithelium cells of the mucosa. For
3+
2+
3+
transfer to the blood serum, reoxidation to Fe is necessary. The oxidation Fe → Fe in the
+
mucosa is catalysed by a copper enzyme (ceruloplasmin, containing 7 copper centres: Cu →
3+
2+
Cu ). The Fe ions are then taken up by apotransferrin (H 2Tf); simultaneously, carbonate is
3+
coordinated to iron. Fe -Tf is the transport form for iron. The iron-loaded transferrin, Fig. 3)
delivers iron to sites of potential use (e.g. incorporation into protoporphyrin IX and generation
of haemoglobin), or stored in iron storage proteins (ferritins). The delivery of iron affords
reduction from the ferric to the ferrous state; a reductant employed here is ascorbate (vitamin
C):
-
3+
+
-
III
uptake: H 2Tf + Fe + HCO 3 → [(Tf)Fe (CO 3)] + 3 H
III
2+
-
+
-
-
release: [(Tf)Fe (CO 3)] + e + 3 H → H 2Tf + HCO 3 + Fe
+
2+
usage: Fe + (protoporphyrin-IX) + globin → haemoglobin + 2H

The daily absorption rate of iron supplied by food amounts to ca. 1 mg. Within our organism,
about 40 mg of Fe are mobilised and transported by Tf into the spinal marrow for the
haemoglobin synthesis, and about 6 mg are stored within or mobilised from the ferritins (vide
infra). Transferrin is a glycoproteid of molecular weight 80 kDa (containing ca. 6%
carbohydrate), having available two almost equivalent binding sites for iron(III), in the C- and
N-teminal lobes, respectively. The pK (K = stability constant; see inset on p. 5) at pH 7.4 (the
pH of blood) is -20.2. Transferrin is also an effective transporter for other tri- and divalent
metal cations, and even for anions (e.g. vanadate). Since its loading capacity for iron
commonly is only ca. 40%, other ions can be transported simultaneously.
Arg NH 2
HN
NH 2

O

Tyr O
O O
Fe
O O
Asp N Tyr 3+
O Figure 3: The Fe -carbonate-transferrin complex.
Coordination of carbonate(2-) is supported by salt
NH
interaction with an arginine residue in the protein
His pocket.

Ferritins (Fig. 4) are iron storage proteins, built up of a hollow protein sphere (apo-ferritin, M =
450 kDa, 24 subunits of 163 amino acids each) with an outer diameter of 130 and an inner
diameter of 70 Å. The inner surface of this capsule is lined with carboxylate functions, which
3+
3+
can coordinate Fe . Up to 4500 Fe can be taken up. The various iron centres are connected
by bridging oxido and hydroxido groups very much as in the colloidal form of ferric hydroxide
(see above) or the mineral goethite. The overall composition of the iron nucleus is
8FeO(OH)·FeO(H 2PO 4). Channels of threefold symmetry and a width of 10 Å allow for an
3+
exchange of Fe between the interior and exterior. For the primary uptake process, iron has to
be in the oxidation state +II. Its transport along the channels and built-in into the core is
accompanied by oxidation to the +III state: