Chemistry Reference
In-Depth Information
Macrophage
Enterocyte
Ferroportin
Ferroportin
Lysosomes
Hepcidin
Hepcidin
FIGURE 22.2
Hepcidin and haemochromatosis. The activity of hepcidin is depicted, showing ferroportin as a target both on enterocytes and
macrophages. Hepcidin binds to ferroportin triggering its internalisation and lysosomal degradation.
(Adapted from
Andrews, 2008
.)
FIGURE 22.3
Model for liver-centred serum iron sensing.
(From
Schmidt, Toran, Giannetti, Bjorkman, & Andrews, 2008
. Copyright 2008
with permission from Elsevier.)
The primary aim of chelation therapy is to remove iron from the body at a rate which is either greater than
transfusional iron input (reduction therapy) or equal to iron input (maintenance therapy).
The structures of the three iron chelators which are currently approved for clinical use are presented in
Figure 22.4
. It is now well established that iron chelation therapy reduces the risk of death and improves patient
survival during more than four decades of clinical experience with the current reference standard chelator, des-
ferrioxamine (DFO). DFO is a hexadentate chelator (as we saw in Chapter 2). However, it is not active by oral
function is to restore homeostasis by interacting with a specific target/receptor. (b,c) Homeostatic regulation of glucose and iron metabolism.
(d,e) Disruption of homeostasis: diabetes and haemochromatosis. (d) Defective insulin production (caused by immune-mediated or secondary
destruction of pancreatic beta cells or genetic defects that impair glucose sensing or insulin synthesis) or reduced insulin sensitivity can cause
unchecked increases in blood glucose levels and diabetes. (e) Similarly, defective hepcidin synthesis (caused by a massive loss of hepatocytes or
genetic and acquired factors that impair iron sensing or hepcidin synthesis) or reduced hepcidin sensitivity can lead to progressive increases in
serum iron levels and haemochromatosis.
(From
Pietrangelo, 2007
.
Copyright 2007 with permission from Wiley-Blackwell.)
