Iron Use and Cycle Flashcards
Which form of Iron is absorbed? How is it transported into enterocyte?
Ferrous (2+), via DMT1 (divalent metal transporter)
What are the two sources of iron coming into enterocyte?
Iron from food we eat and free iron coming in as heme molecule
This molecule stores excess mineral iron and has an outside protein coat
Ferritin (ferr, tin = a tin to store iron)
This green bile pigment is a result from the breakdown of heme of hemoglobin in erythrocytes
Biliverdin
This molecule transports iron out of cell
Ferroportin
After leaving the enterocyte via ferroportin, ferrous iron gets converts to ferric form via this protein
Hephaestin
The name of this transport glycoprotein when not bound to iron
Apo-transferrin
Transport protein when bound with 2 irons
Transferrin
What is every cell using heme for?
Electron transport chain! Every ETC protein has heme in them. Used to transport electrons
Endocytosis of transferrin relies on this receptor in which type of cell?
TfR (Transferrin receptor), in erythroblast
What state of iron binds to transferrin?
Ferric state (3+), two irons per transferrin
What happens to transferrin after endocytosis in erythroblast?
Tranferrin molecule gets released via TfR, and now called “Apotransferrin” gets reused
Once transferrin binds to TfR receptor on erythroblast, how does it enter cell?
Endocytosis
Once in erythroblast, Fe3+ gets converted to Fe2+ and is mainly used to make
Makes heme for hemoglobin
Why does macrophage need iron?
serves as internal storage of extra iron for body
What are macrophage’s two sources of iron?
Engulfing RBCs (that contain iron in heme to make up hemoglobin), and uptake of transferrin via TfR
If other parts of body need iron, iron leaves the macrophage via this transporter
ferroportin
Hepatocytes (liver cells) store iron as
Ferritin
Iron in hepatocyte (liver cell) can be moved out via
Ferroportin
Where is apotransferrin made?
in liver cells! Livers contain nucleus and so can do transcription and translation to make apotransferrin that can bind to iron.
Why is it a problem if you’re absorbing too much iron?
No way of regulating it. Only way to get rid of excess iron is shedding of epithelial cells in GI tract and skin. Can be a problem if you have too much, because can damage bodily organs
What are there iron complications in sickle cell anemia?
Patients need RBCs so get frequent blood transfusion. Often times can become iron overloaded. Need RBCs but not iron!
Where is the “thermostat” located that evaluates the corresponding amount of iron out in circulation?
Hepatocyte (liver cell)
This peptide hormone is the master regulator of iron hemostasis. Where is it made?
Hepcidin, made in liver
How does Hepcidin work when thermostat senses iron excess? What does it bind to?
Hepatocytes produce and excrete hepcidin» hepcidin binds to ferroportin on hepatocytes, enterocytes, and macrophages»internalization and destruction of ferroportin»inhibits iron export
ferrous iron gets converted to ferric form via this protein after leaving either macrophages or hepatocytes
Ceruloplasmin
Enteroctyes help regulate iron levels by inhibiting this transporter
DMT1
This element regulates iron levels within the mRNA coding for DMT1, Tfr, and apo-ferritin
Iron response elements (IREs)
when there are low apotransferrin iron levels, IRE+IRP increase/decrease DMT1 and Tfr levels
increases (up regulates DMT1 because you want enterocytes to take in more iron, and up-regulate Tfr because you want erythroblasts, macrophages, and hepatocytes to take in more iron)
Cytoplasmic iron in the corresponding cell binds to this protein that then binds to IREs to help regulation
Iron response proteins (IRPs)
What amount of all body iron exists within hemoglobin?
2/3
If you lose blood, iron levels will (increase/decrease) in circulation
decrease
if you lose iron, serum iron will (increase/decrease)
decrease
If you lose iron, ferritin levels (inside ~ correlate with serum levels) increase/decrease
decrease. if iron drops, macrophages and hepatocytes in response will move iron out of ferritin, into iron pool, and into circulation for what’s being lost
If iron levels decrease, apo-transferrin levels (increase/decrease)
increase. When macrophages and haptocytes move iron out of ferritin and into circulation pool, hepatocytes will increase the amount of apotransferin, hoping that more iron is coming in through GI tract
If iron levels decrease, serum transferrin (increases/decreases)
increases. More iron released out into circulation
Total iron binding capacity (TIBC) is an indirect measure of?
Transferrin
If iron levels decrease, TIBC (total iron binding capacity) increases/decreases
increase
Overall: Decreasing serum iron causes ____ in serum ferritin, ____ in serum transferrin, and ____ in total iron binding capacity
decrease in serum ferritin, increase in serum trasnferrin, an increase in TIBC
Chronic inflammatory cytokines can cause an increase leakage of what out of cells?
Ferritin. This is important because inflammatory cytokines block release of iron from ferritin. Iron can be stored, but doesn’t get released. So ferritin leaks out, and serum ferritin levels appear to be normal (which is an indication of iron levels), but iron is trapped.
Which cell doesn’t contain a TfR (transferrin receptor) on membrane?
Enterocyte (duodenum). Transporter for iron in heme is unidentified and Fe2+ enters via DMT1.
This amount of iron is absorbed daily by GI and lost daily from shedding of epithelial cells
1-2 mg
Daily RBC/hemoglobin production and other use of iron requires how much iron per day? What does this suggest?
25 mg. The majority of body iron is recycled
low ph and iron chelators (i.e. Vitamin C) increase/decrease iron absorption
increase iron absorption
