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59 Cards in this Set

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  • Back
Where is most of the iron stored in the body? (more iron is in use, but wheres the primary storage site)
in resident macrophages
Can the body promote iron loss?
no it cannot, the body can only lose iron by bleeding
What is the scale of bioavailbility of iron, from its 4 forms
Heme>>> Ferrous Fe2+>Ferric Iron Fe3+>elemental iron Fe0
What is a major source of heme iron? how available is it?
Heme iron is VERY bioavailable

it is found in meats, and fish, and seafoods
What is the major source of Non-heme iron?
vegetables, fruits and egs
What are the solubility properties and bioavailability of Ferric Iron Fe3+
this is insoluble at biological pH, and is not very bioavailable

requires stomach acid to solubilize it
What are the solubility properties and bioavailability of Ferrous iron Fe2+
this is bioavailable, and it IS soluble at biological PH

(contained in iron supplements)
What are the solubility properties and bioavailability of elemental iron?
this is poor at both

needs acidic PH to solubilize
What 3 major groups of things increase Iron uptake?
Reducing molecules
Amino Acids
Acidic foods
How does vitamin C help with iron uptake?
this converts ferric iron Fe3+ into ferrous iron Fe2+
What form of iron can from complexes with Vitamin C, AA's, and glucose. how does this affect absorption?
these bind Ferrous Iron Fe2+

this makes it MORE bioavailable
How do Phytates affect iron absorption?
what contains phytates?
these inhibit iron absorption, by forming chelates with divalent cations

common in high cereal grains, legumes
how do polyphenols affect iron absorption? where are they found?
these inhibit iron absorption, by forming chelates with divalent cations

common in Tannic acid, from tea and coffee. Decrease iron uptake by 40-60% respectively
how do phosphates and phosphoproteins affect iron absorption?

where are they found?
These bind Ferrous Fe2+, and Ferric Fe3+

these are found in egg yolk
how does Oxalate affect iron absorption? where is it found?
These chelates non-heme iron (Fe2+ and Fe3+)

found i spinach, (which makes the iron in spinach not available for uptake)
how do Calcium and Zinc affect iron uptake? in what concentrations?
500mg or more of Calcium

or 5X the iron levels of Zinc

both inhibit iron uptake
What does Transferrin do?
this is a serum protein that Transports iron, in circulation
How does Non-heme iron get absorbed into enterocytes?
this is taken up by DMT1
How is heme iron absorbed into enterocytes?
this is directly taken up as heme, and once inside the cell, is broken down by Heme Oxygenase (HO-1)

this releases the iron in heme
in the enterocytes, what does mobilferrin do?
this transports Fe trough the cell, for use in other processes
in the enterocytes, what does ferritin do?
this is an iron storage site....it can cause iron loss if this isnt used, and the entrocytes die off.
How is iron exported from the enterocyte?
this occurs on the basal side, via Ferroportin
What cells contain Ferroportin?
ONLY duodenal enterocytes, macrophages, hepatocytes, and trophoblasts of the placenta
What is the Fenton reaction?
this is a toxic reaction involving Ferrous Iron (Fe2+) , this splits Hydrogen Peroxide into two hydroxyl radicals (while converting itself into ferric iron Fe3+)
What is Transferrin, what is it job, and where is it found
This binds ferric iron outside the cell (Fe3+)

its job is to:
Solubilize iron
Stop reactivity
deliver iron to usage and storage sites
What are the 3 states of transferrin?
apo-transferrin (no iron bound)
monoferric transferrin
diferric transferrin
what do all growing cells require?
IRON yay!
How does iron cross a lipid bilayer to enter a regular cell?
this uses a transferrin receptor, and its process of endocytosis.
what type of transferrin does the transferrin receptor have a high affinity for?
diferrictransferrin
How is iron released from transferrin once endocytosed?
there is an H+ pump in the endosome that acidifys the interior. this releases the stored iron
how much iron is in storage in a healthy person?
about 25%
What does Ferritin do, and where is it found?
This is an intracellular protein found in all cells,
and it is used to store iron.
What forms does ferritin come in?
this is a 24 subunit polypeptide
has H and L subunits, found in various ratios
how much iron can a single ferritin store?
up to 4500 atoms of iron
can the iron store inside ferritin participate in the fenton reaction?
no it cannot
What is the BEST test to assess body iron stores?
measuring Serum Ferritin Levels
What is hemosiderin?
This is a form of ferritin, that has been partially degraded by lysosomes. contains 30% more stored iron than Ferritin
what is hemosiderin a sign of?
this is a sign of iron overload
What is Ferroportin, where is it found?
this move iron OUT of the cell, and into circulation, it is found only in

Macrophages- iron from RBC breakdown

Hepatocytes- Iron from storage

Duodenal Enterocytes- iron from diet

Placental Trophoblasts- iron to embryo
What is Hepcidin?
this is a 25aa peptide, this control iron absorption and mobiliztion
How do hepcidin levels affect ferroportin?
High levels of hepcidin, BIND to ferroportin, preventing the 4 cell types from releasing iron, AND absorption of iron

aka induces internalization and degradation of ferroportin
What kinds of things induce hepcidin production?
Increased iron stores, increased plasma iron levels.

Infection and inflammation

(this causes less iron to be released, by binding and degrading ferroportin)
what kinds of things inhibit hepcidin production?
decreased iron stores
hypoxia
increased RBC demand (this is an overriding signal- like in blood loss)
What are IRE's?
these are stem-loop structures in the mRNA, that code for Iron-regulated proteins
What IRE's are in the 5'-UTR?
ferritin and ALA-S2
what IRE's are in the 3' UTR?
Transferrin receptor, or DMT1
what are IRPs?
these are cytosolic proteins that bind to IRE, with high affinity, but have an even higher affinity for Iron
What does an IRP bound to a 3' IRE do?
this stabilizes the mRNA, increasing the level of protein synthesis
what does an IRP bound to the 5' IRE do?
this prevents DNA translation, decreasing protein synthese
how do IRP's function?
IRP's are sensitive to iron, so in LOW iron- IRP's are avtive, and bind the IRE's on the mRNA.

When iron is High, all IRP's are bound by iron, and the its ability to bind IRE's is impaired
What happens to the IRE's, IRP's and their gene products when iron is high?
IRE's are unbound
Ferritin synthesis is increased
increases iron storage
transferrin synthesis is decreased
What happens to the IRE's, IRP's and their gene products when iron is low?
IRE's are bound by IRP's
ferrtin synthesis is decreased
increased export
transferrin receptor is produced
how does iron affect infection?
this makes infections WORSE in high levels
What is lactoferrin? what makes it, and when is it used?
this is a natural defense iron binding protein. it is similar to transferin.

synthesized by neutrophils, released during infection and inflammation
VERY high affinity for iron, more than transferrin
What does IL-1 stimulate?
-This encourages nutrophils to produce lactoferrin.
- increases RBC phagocytosis
- slows down erythropoiesis
what does IL-6 do?
this stimulates liver to release hepcidin, which lowers ferroprotin levels, and decreases overall iron in the blood
what causes anemia of chronic disease?
chronic high levels of hepcidin
How much iron does 1 ml of blood contain?
.5mg iron/1ml blood
what is the most common cause of iron deficiency in the US?
acute or chronic blood loss