Chemistry Reference
In-Depth Information
FIGURE 14.17
Reduction of N
2
O at the Cu
Z
site. (From
Chen et al., 2004
.
Copyright 2004 with permission from Nature publishing.)
MARS AND VENUS
e
THE ROLE OF COPPER IN IRON METABOLISM
Very early studies established that copper deficiency is associated with anemia in a number of animals. However, the
key to understanding the interaction between copper and iron came from the observations that in yeast, mutations
affecting copper metabolism blocked the high affinity iron uptake system. Whether the mutations were in the plasma
membrane copper transporters or in the copper chaperone P-type ATPase Atx1, which inserts iron into the Fet3
oxidase, the outcome was the same, and for the same reason
a multicopper oxidase is required for high affinity
iron uptake into yeast. It then came as no surprise to find that in the rare human neurological disease acer-
uloplasminaemia, iron accumulated in brain and liver, indicative that Chapter 7) a key role of ceruloplasmin was in
tissue iron mobilisation. This was convincingly shown by studies in which the yeast Fet3 oxidase was shown to
restore iron homeostasis in aceruloplasminemic mice (
Harris et al., 2004
). The likely mechanism is shown in
Figure 14.18
,
in which the export of iron via the Fe
2
รพ
transporter ferroportin is thought to require the ferroxidase
activity of ceruloplasmin to ensure its incorporation into apotransferrin. For further details see
Crichton & Pierre,
2001
;
Crichton & Ward, 2006
; Crichton, 2009;
Hellman & Gitlin, 2002
.
e
FIGURE 14.18
Representation of the role of ceruloplasmin in mobilising iron from reticuloendothelial cells. (From
Hellman & Gitlin, 2002
.
Copyright 2002 with permission from Annual Reviews.)
