Page 31 - Academic Press Encyclopedia of Physical Science and Technology 3rd InOrganic Chemistry

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Encyclopedia of Physical Science and Technology EN002F-55 May 22, 2001 21:6

Bioinorganic Chemistry 119

FIGURE 1 General scheme of metal ion uptake and regulation.

1. Iron Regulation in E. coli Studies on eukaryotes show that there is a mechanism
for iron storage in these cells when the concentration of
The Fur (ferric uptake regulation) protein negatively reg-
iron in the cell increases. This process is regulated at the
ulates the production of the siderophore enterobactin.
translational level (Fig. 1).
Siderophores are small molecules that chelate Fe(III)
in the environment and are then transported across the
2. Iron Regulation in Humans
cell membrane, introducing Fe(III) into the cell. Most
siderophores use catechol or hydroxamate groups to bind In humans, iron is transported across the gut by a series of
Fe(III). Unicellular organisms must make siderophores in poorly defined processes. Fe(III), ferric ion, is absorbed
order to extract the highly insoluble Fe(III) from ores or via a β 3 integrin and mobilferrin, whereas ferrous ion en-
rust. At low intracellular levels of iron, the Fur protein ter the cells via Nramp. Once inside the body, Fe(III)
does not bind DNA, and proteins that are responsible for is transported through the serum by transferrin, a pro-
the synthesis and transport of enterobactin across the cell tein of molecular weight 63,000 Da. Fe(III)•transferrin
membrane are produced. As the levels of iron are elevated, is recognized by a receptor protein on the cell surface.
it binds to DNA and blocks the expression of these pro- Via a process known as cell-mediated endocytosis, the
teins, halting the intake of iron when the concentration Fe(III)•transferrin/receptor complex induces the external
of iron becomes too high. In this way, iron is directly re- cell membrane to pucker and eventually form a clatharin-
sponsible for transcriptional regulation of the synthesis coated vesicle in the cytoplasm. After removal of the
of siderophores that are responsible for its own uptake. clatharin, the vesicle (known as an endosome) becomes