Term
| Iron in an essential element that when bound in tissues is bound or incorporated into various heme proteins such as: |
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Definition
1) hemoglobin
2) myoglobin
3) cytochromes
4) peroxidases
5) catalases
6) flavoproteins in NADH dehydrogenase |
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Term
| Both iron _______ and iron ______ cause significant disease |
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Definition
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Term
| Proximal intestinal mucosal cell |
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Definition
| This is where iron is absorbed |
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Term
| Iron is transported across the cell and it |
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Definition
| enters the plasma and is delivered to the tissues |
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Term
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Definition
ferric iron (Fe3+)
toxic to cells and also precipitates in the alkaline media of the duodenum and jejunum where iron is best absorbed |
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Term
| Regarding iron regulation, 6 complex systems have been developed |
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Definition
1) chelate ferric iron in the intestine preventing precipitation
2) store iron in a non-toxic form intracellularly
3) transport iron across cell membranes
4) transport iron in the blood in a safe manner
5) reduce iron intracellularly so it can be used for heme synthesis
6) regulate absorption |
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Term
| 3 major determinants of iron absorption are |
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Definition
1) total body iron stores
2) hypoxia
3) level of erythropoiesis |
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Term
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Definition
| this can also have a profound effect on iron absorption and metabolism and is significant clinical issue for many individuals |
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Term
| regulation of absorption, uptake, and macrophage release of iron is regulated by 2 things: |
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Definition
1) primarily by hepcidin protein which is made in the liver
2) by messenger RNA modification of key proteins by the IRE/IRP network |
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Term
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Definition
very large cell that undergoes endomitosis (nuclear division without cytoplasmic division) and produces platelets (cytoplasm breaks into many fragments)
one of these can make up to 20,000 platelet fragments |
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Term
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Definition
| this helps generate platelets from megakaryocytes |
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Term
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Definition
| deep invaginations of surface membrane, to prevent bleeding, surface membrane evagniates and will expand, and cellular contents will leave cell by fusing with other components of membrane and the diffuses out of cell |
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Term
| PLT's have 3 types of granules |
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Definition
1) lysosomal
2) Alpha (have hundreds of kinds of proteins in them that assist in blood coagulation)
3) Dense (look dense under electron micrograph bc they have calcium, ADP and ATP) |
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Term
| Important Proteins in Iron Metabolism |
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Definition
1) Transport/Absorption
-Transferrin
-Transferrin receptors (TFR1, TFR2),
-DMT1, Dcytb (ferri-reductase), ferroportin, hephaestin, cerluoplasmin
-HFE
HCPI-heme carrier protein I
2) Storage
-Ferritin
-Hemosiderin
3) Regulation
-Hepcidin, IRP, IRE, hemojuvelin, TFR2, TFR1, HFE, SMAD, BMP
4) Metabolism
-Heme oxidase |
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Term
| different general ways to regulate iron absorption |
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Definition
-crypt regulation
-hepcidin
-hypoxia/anemia
-erythropoiesis
-inflammation
-body iron stores |
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Term
| Heme synthesis requires how many enzymes? |
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Definition
8
4 in cytoplasm
4 in mitochondria |
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Term
| ALA synthase (ALA-Aminolevulinic acid synthase) |
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Definition
| an enzyme necessary in heme synthesis |
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Term
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Definition
| deep invaginations of surface membrane. to prevent blooding, surface membrane evaginates and will expand, and cellular contents will leave cell by fusing with other components of membrane and then diffuses out of cell |
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Term
| The process of cellular Iron uptake (RBC precursors) |
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Definition
| Iron in extracelluar space binds to Apo-Tf, and then both together bind to TfR on the cell membrane. This big complex gets wrapped up into a clathrin-coated vesicle that becomes the endosome that travels into the cytoplasm. The iron lets go of the complex while still in the endosome as the proton pump in the endosome pumps hydrogens inside (makes pH 5.5). The acidified endosome has a DMT1 (divalent metal transporter 1) through its membrane which then allows the iron to get released out of the endosome into the cytoplasm stored as ferritin then to hemosiderin |
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Term
| iron transport out of the macrophage and hepatocyte is by two molecules |
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Definition
| ferroportin and hephaestin |
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Term
| Regulation of iron absorption |
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Definition
-crypt regulation
-hepcidin
-hypoxia/anemia
-erythropoiesis
-inflammation
-body iron stores |
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Term
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Definition
cells at the absortive surface have a phenotype that is driven by level of iron exposure when the cell was in the crypt, mucosal cells in duodenal crypts are exposed to iron in blood, level of absorptive proteins (DMT1) are regulated....
ex.high blood iron results in low levels of DMT1 expression |
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Term
| high blood iron results in ______ levels of DMT1 expression |
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Definition
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Term
| If you have a lot of iron going to the liver will hepcidin be made or inhibited? |
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Definition
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Term
| if you are deficient in iron, have hypoxia, HIF, will hepcidin be made/inhibited? |
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Definition
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Term
| Process of heme degradation |
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Definition
| Heme --> Biliverdin (goes to bilirubin) + Fe (gets stored or recycled) + CO (released to blood and exhaled) |
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