Flashcards in EXAM #1: IRON HEMOSTASIS & PORPHYRIN METABOLISM Deck (62)
What is the typical daily iron requirement from the diet?
*****Note that this comes from heme in animal products, and non-heme (Fe+++) from vegetables.
What patient populations have an increased iron need?
1) Menstruating women
2) Pregnant women
3) Growing children
*****Note that there may be increased need in vegetarians b/c non-heme iron is not easily absorbed****
Why is iron complexed with proteins and biomolecules in the body?
Free Fe++ and Fe+++ would generate damaging ROS
*****Note that Fe+++ is NOT biologically useful and is reduced by RBCs back to Fe++. Oxidation of Fe++ to Fe+++ produces hydroxide radical and superoxide anion*****
What are the functional forms of iron?
4) Other iron containing enzymes
What are the two storage forms of iron?
What is Ferritin?
Storage molecule from which iron is released on demand
What is hemosiderin?
Degenerated iron/protein complex that cannot be metabolized
Clinically, what is hemosiderin in tissues an indication of?
What cells in the body take-up iron?
Enterocytes in the proximal duodenum
What is the role of transferrin in the body?
Binds iron in the plasma for transport
Once iron is in the plasma, what happens to it?
Travels to the bone marrow and is incorporated into RBCs
When is iron stored as ferretin?
Once it has been phagoctosed by splenic macrophages
When iron is released from macrophages on demand, how is it transported?
As transferrin in plasma
What organ stores ferretin iron aside from splenic macrophages?
Liver stores ferretin
How is iron homeostasis regulated?
Iron UPTAKE is regulated at the level of the ENTEROCYTES
Can iron be excreted from the body?
Iron only leaves the body from bleeding or sloughing off of duodenal enterocytes
How is heme iron taken up into the body via enterocytes?
Heme Carrier Protein 1
How is non-heme (Fe+++) iron absorbed?
1) Reduction by enterocyte cytochromep450
2) Uptake by divalent metal transporter (DMT-1)
What is the function of ferroportin?
Transporter that releases Fe++ iron from the enterocytes into the plasma
What regulates whether iron stays in the enterocyte or is transported into the plasma?
Hepcidin from the liver
What is the role of Hepcidin?
Prevents iron transport through ferroportin
Why does the liver want to diminish iron concentrations?
Infectious organisms need iron to grow; this is a strategy to combat infection
Outline the process of transferrin-bound iron uptake into cells.
1) Transferrin-bound iron binds transferrin receptor
2) Clathrin mediated endocytosis into endosome
3) ATPase acidifies the endosome
4) Change in transferrin conformation to release iron as Fe+++
5) Fe+++ is reduced to Fe++
6) DMT-1 transports Fe++ into the cytoplasm
Transferrin receptor is recycled back to the surface of the cell.
Once in the cytoplasm, how is iron stored?
What are the three anatomical locations with the highest concentrations of ferretin-bound iron?
3) Bone marrow
When RBCs are destroyed in splenic macrophages, what happens to the iron? What happens to that iron when it is needed?
- Stored as ferretin in splenic macrophages
- On demand, iron is transported via ferroportin into the circulation
What organ produces hepcidin?
What is the function of hepcidin?
1) Blocks ferroportin in ENTEROCYTES
2) Blocks ferroportin in SPLENIC MACROPHAGES
At what level is ferretin regulated?
Post-transcriptional level via the "Iron Response Element" in the 5' UTR of the mRNA