Iron homeostasis UC - C Flashcards
A notable exception is iron, in which daily dietary absorption is regulated so that it matches daily iron loss.
A notable exception is iron, in which daily dietary absorption is regulated so that it matches daily iron loss.
The reason that absorption must be carefully regulated is that the body does not possess a physiological mechanism for regularly eliminating iron from the body.
The reason that absorption must be carefully regulated is that the body does not possess a physiological mechanism for regularly eliminating iron from the body.
Iron is a necessary component of various enzymes, but its major role is in oxygen-binding as a component of hemoglobin in red blood cells.
Iron is a necessary component of various enzymes, but its major role is in oxygen-binding as a component of hemoglobin in red blood cells.
Iron deficiency leads to anemia, a decrease in the oxygen carrying capacity of blood. However, too much iron in the body can be extremely toxic to tissues because it promotes the formation of free radicals.
Iron deficiency leads to anemia, a decrease in the oxygen carrying capacity of blood. However, too much iron in the body can be extremely toxic to tissues because it promotes the formation of free radicals.
The majority of the body’s iron is found in hemoglobin of developing and mature red blood cells.
The majority of the body’s iron is found in hemoglobin of developing and mature red blood cells.
Of the remaining iron, a significant portion is stored in the liver, both in the hepatocytes, and in the Kupffer cells (also known as reticuloendothelial cells), a type of macrophage found in the liver. Kupffer cells play an important role in recycling body iron. They ingest aged red blood cells, liberating iron for reuse by breaking down hemoglobin.
Of the remaining iron, a significant portion is stored in the liver, both in the hepatocytes, and in the Kupffer cells (also known as reticuloendothelial cells), a type of macrophage found in the liver. Kupffer cells play an important role in recycling body iron. They ingest aged red blood cells, liberating iron for reuse by breaking down hemoglobin.
The small amount of iron that is lost each day (about 1-2 mg) is matched by dietary absorption of iron.
The small amount of iron that is lost each day (about 1-2 mg) is matched by dietary absorption of iron.
Iron is brought into the cell through an active transport process involving the protein DMT-1 (divalent metal transporter-1), which is expressed on the apical surface of enterocytes in the initial part of the duodenum.
Iron is brought into the cell through an active transport process involving the protein DMT-1 (divalent metal transporter-1), which is expressed on the apical surface of enterocytes in the initial part of the duodenum.
DMT-1 is not specific to iron, and can transport other metal ions such as zinc, copper, cobalt, manganese, cadmium or lead.
DMT-1 is not specific to iron, and can transport other metal ions such as zinc, copper, cobalt, manganese, cadmium or lead.
Enterocytes also absorb heme iron through a mechanism that has not yet been characterized.
Enterocytes also absorb heme iron through a mechanism that has not yet been characterized.
Once inside the enterocyte, there are two fates for iron:
It may leave the enterocyte and enter the body via the basolateral transporter known as ferroportin.
It can be bound to ferritin, an intracellular iron-binding protein. For the most part, iron bound to ferritin in the enterocyte will remain there. This iron will be lost from the body when the enterocyte dies and is sloughed off from the tip of the villus.
Once inside the enterocyte, there are two fates for iron:
It may leave the enterocyte and enter the body via the basolateral transporter known as ferroportin.
It can be bound to ferritin, an intracellular iron-binding protein. For the most part, iron bound to ferritin in the enterocyte will remain there. This iron will be lost from the body when the enterocyte dies and is sloughed off from the tip of the villus.
Iron that enters the internal environment of the body from the basolateral surface of the enterocyte is rapidly bound to transferrin, an iron-binding protein of the blood. Transferrin delivers iron to red blood cell precursors, that take up iron bound to transferrin via receptor-mediated endocytosis.
Iron that enters the internal environment of the body from the basolateral surface of the enterocyte is rapidly bound to transferrin, an iron-binding protein of the blood. Transferrin delivers iron to red blood cell precursors, that take up iron bound to transferrin via receptor-mediated endocytosis.
Normally, the capacity of transferrin to bind iron in the plasma greatly exceeds the amount of circulating iron. The transferrin saturation (percent of transferrin occupied by iron) is measured to determine if an individual has an excessive load of iron in the body. The normal transferrin saturation is in the range of 20-45%.
Normally, the capacity of transferrin to bind iron in the plasma greatly exceeds the amount of circulating iron. The transferrin saturation (percent of transferrin occupied by iron) is measured to determine if an individual has an excessive load of iron in the body. The normal transferrin saturation is in the range of 20-45%.
Iron absorption by the enterocyte is programmed to match the body’s needs. There are two major signals that affect iron absorption.
- One signal reflects the need for iron due to erythropoiesis (red blood cell generation). The hormone erythropoietin (produced by the kidneys) stimulates red blood cell production, but it is NOT the signal regulating iron absorption. Rather, once erythropoiesis is stimulated, another signal is generated that promotes increased iron absorption.
- A second signal depends upon the amount of iron in body stores. Iron absorption is stimulated if the level in body stores is low.
These signals (and others) regulate iron absorption in the proximal duodenum, where iron is absorbed. An important player in this regulation is the recently discovered hormone hepcidin. Hepcidin is produced by hepatocytes when iron stores are full. Inflammation can also stimulate hepcidin production.
Iron absorption by the enterocyte is programmed to match the body’s needs. There are two major signals that affect iron absorption.
- One signal reflects the need for iron due to erythropoiesis (red blood cell generation). The hormone erythropoietin (produced by the kidneys) stimulates red blood cell production, but it is NOT the signal regulating iron absorption. Rather, once erythropoiesis is stimulated, another signal is generated that promotes increased iron absorption.
- A second signal depends upon the amount of iron in body stores. Iron absorption is stimulated if the level in body stores is low.
These signals (and others) regulate iron absorption in the proximal duodenum, where iron is absorbed. An important player in this regulation is the recently discovered hormone hepcidin. Hepcidin is produced by hepatocytes when iron stores are full. Inflammation can also stimulate hepcidin production.
Experiments have shown that hepcidin binds to the basolateral iron transporter ferroportin. This causes ferroportin to be internalized and degraded. As a result, more iron remains within the enterocyte. This stimulates ferritin synthesis, so that the iron that enters the enterocyte gets bound to ferritin. This iron is mostly lost from the body when the enterocyte dies.
Experiments have shown that hepcidin binds to the basolateral iron transporter ferroportin. This causes ferroportin to be internalized and degraded. As a result, more iron remains within the enterocyte. This stimulates ferritin synthesis, so that the iron that enters the enterocyte gets bound to ferritin. This iron is mostly lost from the body when the enterocyte dies.
