Flashcards in EXAM #1: IRON HEMOSTASIS & PORPHYRIN METABOLISM Deck (62)
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1
What is the typical daily iron requirement from the diet?
10-20mg
*****Note that this comes from heme in animal products, and non-heme (Fe+++) from vegetables.
2
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****
3
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*****
4
What are the functional forms of iron?
1) Hb
2) Myoglobin
3) Cytochromes
4) Other iron containing enzymes
5
What are the two storage forms of iron?
Ferritin
Hemosiderin
6
What is Ferritin?
Storage molecule from which iron is released on demand
7
What is hemosiderin?
Degenerated iron/protein complex that cannot be metabolized
8
Clinically, what is hemosiderin in tissues an indication of?
Iron overload
9
What cells in the body take-up iron?
Enterocytes in the proximal duodenum
10
What is the role of transferrin in the body?
Binds iron in the plasma for transport
11
Once iron is in the plasma, what happens to it?
Travels to the bone marrow and is incorporated into RBCs
12
When is iron stored as ferretin?
Once it has been phagoctosed by splenic macrophages
13
When iron is released from macrophages on demand, how is it transported?
As transferrin in plasma
14
What organ stores ferretin iron aside from splenic macrophages?
Liver stores ferretin
15
How is iron homeostasis regulated?
Iron UPTAKE is regulated at the level of the ENTEROCYTES
16
Can iron be excreted from the body?
NO
Iron only leaves the body from bleeding or sloughing off of duodenal enterocytes
17
How is heme iron taken up into the body via enterocytes?
Heme Carrier Protein 1
i.e. HCP-1
18
How is non-heme (Fe+++) iron absorbed?
1) Reduction by enterocyte cytochromep450
2) Uptake by divalent metal transporter (DMT-1)
19
What is the function of ferroportin?
Transporter that releases Fe++ iron from the enterocytes into the plasma
20
What regulates whether iron stays in the enterocyte or is transported into the plasma?
Hepcidin from the liver
21
What is the role of Hepcidin?
Prevents iron transport through ferroportin
22
Why does the liver want to diminish iron concentrations?
Infectious organisms need iron to grow; this is a strategy to combat infection
23
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.
24
Once in the cytoplasm, how is iron stored?
As ferretin
25
What are the three anatomical locations with the highest concentrations of ferretin-bound iron?
1) Liver
2) Spleen
3) Bone marrow
26
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
27
What organ produces hepcidin?
Liver
28
What is the function of hepcidin?
1) Blocks ferroportin in ENTEROCYTES
2) Blocks ferroportin in SPLENIC MACROPHAGES
29
At what level is ferretin regulated?
Post-transcriptional level via the "Iron Response Element" in the 5' UTR of the mRNA
30
