EXAM #1: IRON HEMOSTASIS & PORPHYRIN METABOLISM Flashcards Preview

Hematology and Oncology > EXAM #1: IRON HEMOSTASIS & PORPHYRIN METABOLISM > Flashcards

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

Describe how ferretin mRNA responds to free iron in the blood.

- Ferretin mRNA contains the IRE bound to Iron Regulatory Proteins (IRPs)
- Bound IRPs BLOCK translation
- Free iron binds IRPs, allowing for the translation of ferretin mRNA