Chemistry Reference
In-Depth Information
frequently in the long cytoplasmic loop between transmembrane domains 3 and 4. In contrast, most CDF
transporters have six predicted transmembrane domains, a His-rich domain in the loop between domains 4 and 5;
but here the N- and C-termini are on the cytoplasmic side of the membrane.
In the yeast S. cerevisiae, at least four different transporters are involved in zinc uptake. The most important of
these is the ZIP family member ZRT1, which is required for growth under low zinc concentrations. ZRT1 has
a high affinity for zinc with an apparent K
m
for free Zn
2
þ
of 10 nM. A second ZIP protein, ZRT2, with a lower
affinity for zinc (apparent K
m
~100 nM) probably plays a role under less severe zinc limitation. In addition to the
two ZIP proteins, two other lower affinity systems also operate. One is the FET4 protein, which we saw earlier is
also involved in the low affinity uptake of iron and copper.
In dicotyledon plants, like Arabidopsis, acidification of the soil would result in an increase in the solubility of
both zinc and copper. Cu is taken up by the Cu
þ
transporter COPT1, the Arabidopsis orthologue of the yeast
copper transporter CTR1 and is probably reduced by FRO2, which is also responsible for iron reduction. Zn is
most likely taken up by members of the ZIP family, some of which are root specific, while others are found in both
roots and shoots.
In monocotyledon plants, there is no suggested role for phytosiderophores in Cu uptake, and as in dicotyle-
dons, it is probably taken up as Cu
þ
by COPT1. In addition, plants of this group may also take up Cu as Cu
2
þ
via
a member of the ZIP family. ZIP2 and ZIP4 are upregulated by Cu deficiency. In contrast, there is good evidence
for the involvement of mugeneic acids in absorbing Zn from the soil.
METAL ASSIMILATION IN MAMMALS
Since in mammals, metals need first to be assimilated from dietary sources in the intestinal tract and subsequently
transported to the cells of the different organs of the body through the bloodstream, we will restrict ourselves in
this section to the transport of metal ions across the enterocytes of the upper part of the small intestine (essentially
the duodenum), where essentially all of the uptake of dietary constituents, whether they be metal ions, carbo-
hydrates, fats, amino acids, vitamins, etc., takes place. We will then briefly review the mechanisms by which metal
ions are transported across the plasma membrane of mammalian cells and enter the cytoplasm, as we did for
bacteria, fungi, and plants. The specific molecules involved in extracellular metal ion transport in the circulation
will be dealt with in Chapter 8.
1.
Iron
Within the intestinal tract of mammals, dietary iron is essentially in two forms, haem iron and non-haem, ferric,
iron. Haem iron is generally more readily absorbed than non-haem iron, reflecting no doubt the origins of many
mammals (including man) as hunters. Non-haem iron from sources such as vegetables, tend to be a poor source
of iron, because of the presence of phosphates, phytates, and polyphenols, which form stable, insoluble ferric
complexes and decrease absorption. Haem iron is taken up by an as yet elusive specific transporter, and Fe
2
þ
is
then released into the intracellular iron pool by haem oxygenase, which degrades haem to Fe
2
þ
, porphobili-
nogen, and CO (
Fig. 7.17
)
. Non-haem dietary iron is taken up in a manner reminiscent of the low affinity iron
uptake pathway in yeast. Fe(III) is reduced to Fe(II) by a ferric reductase (Dcytb) at the apical membrane and
the Fe(II) is transported into the intestinal cell by DMT1, a proton-coupled divalent cation transporter. Within
the intestinal cell, iron enters a low-molecular-weight pool: some of it may be stored in ferritin, while some of
it can cross to the basolateral membrane. There it can be transferred to the circulation by a transmembrane
transporter protein, ferroportin. In the circulation, serum iron is transported as diferric-transferrin (Tf),
described below and in Chapter 8. It has been suggested that iron incorporation into apotransferrin might be
facilitated by the oxidation of Fe
2
þ
to Fe
3
þ
. Two candidates for this ferroxidase activity have been proposed
(
Fig. 7.17
)
ceruloplasmin (CP), the principal copper-containing protein of serum, or hephaestin, a member of
the family of multicopper oxidases (which includes ceruloplasmin), which appears to be bound to the baso-
lateral membrane.
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