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104 Cards in this Set
- Front
- Back
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Name 6 things Fe is used for
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O2 Storage:Mg
O2 Transport: Hg Cytochrome: respitation Ribonucleotides Oxidative Stress Protection CPY450: drug metabolism |
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What is the only way to excrete Fr? Is there any voluntary way to excrete Fe?
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Sloughing of cells
Nope *also you poo out the nondigestible forms of Fe |
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What cell is Fe stored in?
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Macrophage
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What is the interplay btwn Fe in BM and Macrophages?
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RBC are degraded by macrophages and the Fe they contain is stored here. The BM uses the Fe from macrophages to make new RBC
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About what % of Fe is being used? Where is it used?
About what % of Fe is stored? Where is it stored? |
Use: 75%. Majority is in Hg in RBC, the rest is myoglobin, respiratory cytochromes, ribonucleotide synthesis, protection from oxidatice stress, and drug metabolism
Storage: 25%. macrophages, BM, Spleen, Liver |
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How can Fe levels be decreased?
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Bleeding
natural involuntary sloughing of skin and intestinal epithelium |
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What is the most bioavailable form of Fe? least? List the forms of Fe from most to least bioavailable
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Hemme
Fe+2 (ferrous) Fe+3 (ferric) Fe 0 (elemental) |
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The most bioavailable form of Fe is _____, BUT it can undergo which reaction. What is the consequence of this reaction
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Fe+2 (ferrous) is most bioavailable
But Fe +2 (ferrous) can undergo the FENTON reaction. This creates free radicles from H2O2 |
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What reaction causes free radicles. What form of Fe is used. What Free radical is formed?
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Fenton
Fe+2 (ferrous, most bioavailable) Creates OH* SUPER reactive |
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How can you eat a bioavailable form of Fe?
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Eat heme
Found in meats, fish, seafood |
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Ferric Fe
oxidative state? bioavailability? abundance in food? |
Ferric is +3
not bioavailable. Requires acidic stomach for abs Most abundant in food sources. |
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How can Fe+3 be solubilized for absorption?
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By increased acid in the stomach. It then complexes with other molecules to it will become solubilized even in basic enviornments
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How can Fe levels be decreased?
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Bleeding
natural involuntary sloughing of skin and intestinal epithelium |
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The most bioavailable form of Fe is _____, BUT it can undergo which reaction. What is the consequence of this reaction
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Fe+2 (ferrous) is most bioavailable
But Fe +2 (ferrous) can undergo the FENTON reaction. This creates free radicles from H2O2 |
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Ferric Fe
oxidative state? bioavailability? abundance in food? |
Ferric is +3
not bioavailable. Requires acidic stomach for abs Most abundant in food sources. |
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How can Fe+3 be solubilized for absorption?
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By increased acid in the stomach. It then complexes with other molecules to it will become solubilized even in basic enviornments
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Achlorhydrai is what?
How does it affect Fe abs? Do antacids have the same or opposite affects? |
This decreases HCL in the stomach
This will decrease Fe abs (especiallt of Fe+3, ferric Fe) Antacids also decrease stomach pH and so will decrease Fe abs |
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Ferrous Fe
oxidative state? bioavailability? abundance in food? |
+2
BIOAVAILABLE! can be solubilized at physiological pH commonly found in Fe supplements (ferrous salts) |
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Elemental Fe
oxidative state? bioavailability? abundance in food? |
0
not bioavailable stable, inhert. Used to fortify food? |
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Can the abs of heme Fe be altered?
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NOPE. The porphoryn ring protects it
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Can the abs of non heme Fe be altered?
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Yep!
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What substances will increase abs of Fe. What type if Fe needs to have enhanced abs?
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Non Heme, Fe +3 is biounavailable and can have its abs increased by:
1. Reducing Molecules: reduce Fe+3 to Fe+2 2. Amino Acids 3. Acidic Foods: increase acid levels so its easier to solubilize Fe+3 |
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More charge on Fe make is easier or harder to abs?
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Harder! Fe+3, ferric, Fe is hard to abs
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What will eb the effect of Fe abs when you eat aa?
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increase Fe abs
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What will be the effect of Fe abs with you increase the amt of vitamin c you eat?
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increase Fe abs
Fe+3 reduced to Fe+2 |
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What will happen to Fe abs when you eat acidic foods?
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Increased Fe abs
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Name the 5 things that will inhibit the abs of Fe?
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1. Phytates
2. Polyphenols 3. Phosphates/Phosphoproteins 4. Oxalate 5. Cacluim |
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Will eating spinach increase or decrease Fe abs?
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Spinach has LOTS of Fe, BUT it cant be abs well because it also has lots of Oxalate which inhibits Fe Abs
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Will eating cereal grains increase or decrease Fe Abs?
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It will decrease Fe Abs
**Cereal grains contain, Phytates. Phytates have lots of Pi that bind Fe which makes it hard to abs |
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What cmpd to legumes and cereal grains contain? What is its effect on Fe abs?
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Phytates
Decrease Fe abs by binding Fe to insoluble Pi |
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What is a polyphenol? What is a common polyphenol? What do polyphenols do to Fe abs?
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tannins in coffee and tea
decreases Fe abs |
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What protein contains lots of Phosohates/phosphoproteins? What does this do to Fe abs?
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Egg yolk
Decreases Fe Abs |
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What do oxolates do to Fe abs? waht food has lots?
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Decrease Fe abs
Found in spinach |
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What does Ca do to Fe abs?
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Decreases
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Name the 3 factors that increase Fe bioavailability
Name the 5 factors that decrease Fe bioavailabilty |
Enhancers of Fe Abs
1. Reducing Molecules 2. Amino Acids 3. Acidic Foods Inhibitors of Fe AbS 1. Polyphenols 2. Oxalate 3. Ca 4. Phosphates/Phosphoproteins 5. Phytates |
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Transferrin:
Ferritin: Ferroportin: Hepcidin: Lactoferrin: Factoferrin: |
Transferrin: in serum, transports Fe
Ferritin: intracellular Fe storage protein (found in all cells but esp abundant in macrophages of spleen, BM, liver) Ferroportin: the only way Fe can leave a cell. Found in only 4 cell types (macrophage, hepatocyte, enterocyte, trophoblast) Hepcidin: binds ferroportin and closes it so no Fe can leave macrophages, hepatocytes, enterocytes, trophoblast)) Lactoferrin: used when fighting infection |
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Fe Absorption (abs)
Fe uptake |
Abs: abs of Fe from food through the enterocytes and into circulation
Uptake: from circulation into the body tissues |
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When Fe is needed what happens?
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Fe is in the cell bound with ferritin. Ferroprotein and hepcidin then mobilize the Fe out of the cell and into circulation
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How is heme Fe taken into the enterocytes?
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heme is taken up intact and then is degraded by heme oxygenase and lets free Fe be inside of the enterocyte
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how is NON heme Fe taken into the enterocytes?
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DMTI on the enterocyte lets non heme Fe into the cell.
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What are the three things that Fe can do once it enters the enterocyte?
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1. be used in Fe containing cmpds
2. Bind Ferritin for storage 3. Leave via ferroportin |
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How does Fe move in the enterocyte?
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bound to mobilferrin
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What happens to ferritin
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Ferritin is the storage molecule of Fe in the enterocyte. Enterocytes slough off every 4 days...So the Fe that is bound to ferritin in the enterocyte is lost in poo
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What are the two Fe transporters in the apical side of enterocytes?
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Heme: nondescript carrier
NonHeme: DMT1 |
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How does Fe leave the enterocyte? Is this protein found anywhere else?
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Ferroportin is the export molecule so fe can leave the enterocyte and enter circulation.
Ferroportin is also found in macrophages, hepatocytes, and trophoblasts of the placenta |
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Where is Ferroportin found
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1. hepatocytes
2. macrophages 3. enterocytes 4. trophoblasts of the placenta |
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Can Fe freely leave any cell that it wants to?
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NO. The only way for Fe to leave is via Ferroportin which is only found in macrophages, enterocytes, hepatocytes, and trophoblasts of the placenta
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What form of Fe is toxic?
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Fe+2 Ferrous (the kind that is bioavailable)
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When Fe is in the body what form is it in? What is it complexed with?
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Fe+3 Ferric is in the body and it is complexed with protein
In the blood it is complexed with tranferrin In the enterocyte it is complexed with mobilferrin |
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What is the fenton rxn?
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Fe+2 + H2O2 ---> Fe+3 + OH*
DANGEROUS! TOXIC! |
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What are 3 functions of transferrin? What is the oxidation state of bound Fe?
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1. solubilize Fe
2. decreases the reactivity of Fe 3. Delivers Fe from blood to sites of use and storage ***Fe+3 Ferric is bound! Fe+3 is SAFE |
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What are the different types of transferrin? How many Fe can bind?
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Two Fe can bind
Diferric: 2 Fe+3 bound, this is the form recognized by transferrin receptors Monoferric: one Fe+3 bound Apo-Transferrin: NO Fe+3, bound, picks up Fe that is released from macrophages, enterocytes, hepatocytes (these have ferroportin) |
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What cells require Fe
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ALL
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How is Fe released into the blood?
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macrophage, hepatocytes, enterocytes (ferroportin)
*the Fe released will be picked up by Apo-Transferrin |
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How does Fe enter a cell?
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1. Fe is bound to transferrin
2. Fe cant cross, uses transferrin receptor 3. Diferric Transferrin binds to the transferrin receptor 4. The complex is endocytosed into an endosome 5. H+ pumps into the endosome and transferrin drops Fe 6. Apo transferrin and transferrin receptor are returned to the ECF and PM |
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What form of transferrin has the highest affinity for the transferrin receptor?
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deferric transferrin
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How is Fe released from diferric transferrin?
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**remember, diferric transferrin binds to the transferrin receptor (any cell) and the complex is endocytosed into its own vesicle.
H+ pumps into the vesicle and causes transferrin to drop Fe |
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What is returned to the ECF/PM after Fe has been taken into a cell?
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Apo Transferrin
Transferrin Receptor |
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What allows Fe into a cell?
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Transferrin Receptor
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What protein is involved in Fe storage? In what tissues is Fe stored?
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Ferritin: stores Fe in macrophage, liver, spleen, BM
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What are the sites of Fe storage? (4)
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Macrophages
Liver Spleen BM *stored via ferritin, dont forget ferritin is in all cells but is esp abundant in these 4 |
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what protein has H and L subunits?
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Ferrotin.
*there is ALWAYS a mix of H/L the proportions vary. If ALL H or ALL L its pathological |
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In what state doe Fe enter ferritin?
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Ferritin stores Fe in all cells, esp macrophages of Liver, BM, spleen
Fe+2 (toxic) enters and is oxidized to Fe+3, then it is stored in a different form that cant undergo Fenton Rxn |
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How can you assess body stores of Fe
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Plasma Ferritin
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what is hemosiderin?
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ferritin that has been partially degraded by lysosomes
Stores insoluble Fe Found in conditions of Fe overload |
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In which circumstance would it be more likely to see hemosiderin, anemia or hematochomatisis
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hematachromatisis
**hemosiderin is a form of degraded transferrin that stores insoluble Fe and it found with Fe overload |
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What is the only way Fe can leave a cell? what cells are capable of letting Fe leave?
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Ferroportin is the export channel
1. macrophage 2. Hepatocytes 3. Enterocytes 4. placental trophoblasts |
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Where is hepcidin made
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liver
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what controls Fe abs and metabolism
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Hepcidin
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What does hepcidin do?
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Binds to Ferroportin so that it is destroyed, this means no Fe can leave the cells (macrophages, BM, enterocytes, trophoblast)
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What is unique to the macrophages of liver, spleen and BM?
What is unique to macrophages, liver, enterocytes, and placental trophoblast? |
Great Palces of Fe storage: Ferritin
Only way Fe can Leave: ferroportin |
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When Hepcidin is high what happens to Fe stores? What happens to dietary abs of Fe? What happens to Fe levels in circulation?
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Increases
decrease Decreases |
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When hepcidin is low what happens to Fe stores? What happens to dietary abs of Fe? What happens to Fe in circulation?
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Decerase
Increased Increases |
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Ferroportin is degraded by what?
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Hepcidin
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What are the three things that are decreased by high hepcidin levels
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Fe Abs by enterocytes
Fe release by hepatocytes Fe Recycling by macrophages |
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Will hepcidin be high or low during an infection
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HIGH! We will prevent the release of Fe into the blood. Fe in the blood is used by bugs.
Hepcidin will block ferroportin so that no Fe will leave |
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Will hepcidin be high or low in the following?
low O2 Infection/Inflammation Low Fe High Fe |
Low O2: low Hepcidin
Infection/Inflammation: High Hepcidin Low Fe: High Hepcidin High Fe: Low Hepcidin |
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If the HFG gene is intact but an individual experiences high Fe what is going on?
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decreased levels of Hepcidin
**keep in mind only 4 cells have Ferroportin, so when they all dump Fe into the blood there will be a systemic increase in all tissues. |
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What stimulates hepidicin production?
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infection/inflammation
increased Fe stores increased Fe in blood |
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What inhibits hepcidin production?
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low O2
Low Fe stores Low Le in blood INCREASED DEMAND FROM RBC. **most important, will override other signals |
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why does Fe abs increase when Fe stores are low?
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That person has low hepcidin
This means they have more ferroportin, so more Fe can leave enterocytes as more Fe is abs |
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how is Fe homeostasis regilated:
Systemic? Cellular? |
Systemic: hepcidin
Cellular: IRP IRE |
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Fe Response Element (IRE)
Fe Regulatory Protein (IEP) |
IRE: On the mRNA, when Fe is low IRP will bind
IRP: has a HIGH affinity for Fe, will bind to it, otherwise it will bind to IRE |
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is the location of a IRE constant btwn Fe genes?
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NO
The location of the IRE determines if it is inhibitory or stimulatory **if IRE is 5' UTR it will be inhibitory (ferritin) **if IRE is 3' UTR IRE will be stimulatory (transferrin receptor) |
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Describe the role of IRP/IRE for the ferritin gene. Include what happens when Fe is low and high
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Ferritin Stores Fe. When Fe is low we dont need it stored. When Fe is High we want it stored
The IRE is inhibitory (its in the 3' UTR and blocks ferritin transcription when IRP binds When Fe is high, IRP binds Fe and the IRE on ferritin is empty and allows ferritin to be made When Fe is LOW, the IRP will bind to the IRE and block transcription of ferritin. No ferritin is needed because there is no excess Fe that needs to be stored |
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Describe the role of IRP/IRE for the transferrin receptor gene. Include what happens when Fe is low and high
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Transferrin Receptor allows Fe into the cells. When intracelluar Fe is high there is no need for cells to uptake, when Fe is low the transferrin receptor is made so that Fe can enter the cells.
The IRE on the transferrin gene are stimulatory, the mRNA is stabilized with IRP bound When Fe levels are HIGH in the cell. IRP binds to Fe and the transferrin mRNA is destabilized and no transferrin receptor is made When Fe levels are LOW. IRP binds to IRE and stabilizes the mRNA. Transferrin is made. |
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Keep in mind with IRP/IRE the location of Fe concentration is...
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IN the cell
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When Cellular Fe is high...
When Cellular Fe is low... **tranferrin receptor and ferritin gene |
tranferrin receptor is off
ferritin is on transferrin receptor is on ferritin is off |
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Where does transferrin function to reduce Fe availibility to virus? Where does lactoferrin function to reduce Fe availability to virus?
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Transferrin: plasma, lmyph, CSF (fluids in the body)
Lactoferrin: exocrine secretions (fluid that contacts the outside of the body) |
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How is lactoferrin made?
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infection stimulates macrophages
macrophages release IL 1 and IL 6 IL1 acts on neutrophils to make lactoferrin IL 6 acts on the liver to made hepcidin |
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What does IL1 stimulate?
What does IL6 stimulate? |
IL1: neutrophils to secrete lactoferrin
IL6: hepatocytes to make hepcidin |
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What cells make lactoferrin?
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neutrophils
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What has a greater affinity, lactoferrin or transferrin? What is the result of this?
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lactoferrin has a greater and so will steal Fe from transferrin when there is infection. This causes Fe to be stored away in macrophages. The rest of the body becomes hypoferremic
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name two benefits of reducing Fe levels when there is an infection
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1. the bacteria cant grow without Fe
2. Infection increases H2O2 which will increase the likelyhood of the fenton rxn. Reducing Fe reduces free radicals |
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What does lactoferrin do?
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it binds to Fe and brings it to macrophages for storage
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What causes anemia of chronic disease?
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whith chronic hypoferremia there are high hepcidin levels so Fe isnt properly incorporated into the RBC
Microcytic |
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In order to eliminate excess Fe in circulation during infection what two things happen?
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1. increase Fe stores via lactoferrin
2. Lock the Fe in the cells by increasing hepcidin |
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What is the mechanism to eliminate excess Fe?
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NONE
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How much Fe is contained in a drop of blood?
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0.5mg Fe/ml of blood
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What is the cause of Fe deficiency?
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Blood loss...
you loose a TON of Fe when you loose blood. 0.5mg Fe/mL blood |
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What group is often Fe deficient due to nutritional deficiencies?
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Toddlers
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What group of populations have additional Fe needs?
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preggo's!
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Are Fe supplements recommended?
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not for the general population. even though Fe is often deficient excess Fe is dangerous and the cells cannot rid themselves of excess Fe
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Is Fe deficiency due to inadequate dietary intake?
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NOPE, its due to blood loss
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