Iron metabolism disorders may involve a number of genes including
HFE and
TFR2
Transferrin receptor 2 (TfR2) is a protein that in humans is encoded by the ''TFR2'' gene. This protein is involved in the uptake of transferrin-bound iron into cells by endocytosis, although its role is minor compared to transferrin receptor 1.
...
.
Hepcidin
Hepcidin is a protein that in humans is encoded by the ''HAMP'' gene. Hepcidin is a key regulator of the entry of iron into the circulation in mammals.
During conditions in which the hepcidin level is abnormally high, such as inflammation, se ...
is the
master regulator
In genetics, a master regulator is a gene at the top of a gene regulation hierarchy, particularly in regulatory pathways related to cell fate and differentiation.
Examples
Most genes considered master regulators code for transcription factor prot ...
of
iron metabolism
Human iron metabolism is the set of chemical reactions that maintain human homeostasis of iron at the systemic and cellular level. Iron is both necessary to the body and potentially toxic. Controlling iron levels in the body is a critically impo ...
and, therefore, most genetic forms of iron overload can be thought of as relative hepcidin deficiency in one way or another. For instance, a severe form of iron overload, juvenile
hemochromatosis
Iron overload or hemochromatosis (also spelled ''haemochromatosis'' in British English) indicates increased total accumulation of iron in the body from any cause and resulting organ damage. The most important causes are hereditary haemochromatos ...
, is a result of severe hepcidin deficiency. The majority of cases are caused by mutations in the
hemojuvelin
Hemojuvelin (HJV), also known as repulsive guidance molecule C (RGMc) or hemochromatosis type 2 protein (HFE2), is a membrane-bound and soluble protein in mammals that is responsible for the iron overload condition known as juvenile hemochromatosi ...
gene (HJV or RGMc/repulsive guidance molecule c). The exceptions, people who have mutations in the gene for ferroportin, prove the rule: these people have plenty of hepcidin, but their cells lack the proper response to it. So, in people with ferroportin proteins that transport iron out of cells without responding to hepcidin's signals to stop, they have a deficiency in the action of hepcidin, if not in hepcidin itself.
But the exact mechanisms of most of the various forms of adult hemochromatosis, which make up most of the genetic
iron overload
Iron overload or hemochromatosis (also spelled ''haemochromatosis'' in British English) indicates increased total accumulation of iron in the body from any cause and resulting organ damage. The most important causes are hereditary haemochromatos ...
disorders, remain unsolved. So while researchers have been able to identify genetic mutations causing several adult variants of hemochromatosis, they now must turn their attention to the normal function of these mutated genes.
These genes represent multiple steps along the pathway of iron regulation, from the body's ability to sense iron, to the body's ability to regulate uptake and storage. Working out the functions of each gene in this pathway will be an important tool for finding new methods of treating genetic disorders, as well as for understanding the basic workings of the pathway.
So though many mysteries of iron metabolism remain, the discovery of hepcidin already allows a much better understanding of the nature of iron regulation, and makes researchers optimistic that many more breakthroughs in this field are soon to come.
See also
*
Human iron metabolism
Human iron metabolism is the set of chemical reactions that maintain human homeostasis of iron at the systemic and cellular level. Iron is both necessary to the body and potentially toxic. Controlling iron levels in the body is a critically imp ...
*
Iron deficiency anemia
Iron-deficiency anemia is anemia caused by a lack of iron. Anemia is defined as a decrease in the number of red blood cells or the amount of hemoglobin in the blood. When onset is slow, symptoms are often vague such as feeling tired, weak, s ...
References
External links
* http://sickle.bwh.harvard.edu/menu_iron.html
*
{{Authority control
Iron metabolism