Chemistry Reference
In-Depth Information
FIGURE 8.17
Schematics of cellular iron uptake and utilisation.
(Adapted from
Richardson et al., 2010
.)
About a quarter of total body iron is stored in macrophages and hepatocytes as a reserve which can be readily
mobilised for red blood cell formation (erythropoiesis). This storage iron is mostly in the form of ferritin like
bacterioferritin, a 24-subunit protein in the form of a spherical protein shell enclosing a cavity within which up to
4500 atoms of iron can be stored, essentially as the mineral ferrihydrite. Despite the water insolubility of ferri-
hydrite, it is kept in solution within the protein shell, such that one can easily prepare mammalian ferritin solutions
which contain 1 M ferric iron (i.e., 56 mg/ml!). Mammalian ferritins, unlike most bacterial and plant ferritins,
have the particularity that they are heteropolymers, made up of two subunit types, H and L. Whereas H-subunits
have a ferroxidase activity, catalysing the oxidation of two Fe
2
þ
atoms to Fe
3
þ
, L subunits appear to be involved in
the nucleation of the mineral iron core: once this has formed an initial critical mass, further iron oxidation and
deposition in the biomineral takes place on the surface of the ferrihydrite crystallite itself (for a more detailed
discussion, see Chapter 19).
2.
Iron homeostasis in mammals
The regulation of cellular iron homeostasis is to a large degree controlled at the level of the translation of the
mRNAs of proteins involved in cellular iron metabolism (
Rouault, 2006
;
Wallander et al., 2006
). The key players
in this post-transcriptional regulation are two iron regulatory proteins (IRP1 and IRP2), which function as