Iron and Heme Flashcards
What is the form of iron found in veggies?
Fe 3+
Why can’t Fe be found in the free form in the circulation?
forms ROS
What are the two storage forms of Fe?
Ferritin
hemosiderin
The appearance of hemosiderin molecules in tissues is a sign of what?
Fe overload
What is the form of Fe found in the blood when it is being shuttled from the enterocytes?
Transferrin
Where does Fe go to be made into heme?
Erythroid precursors
Where is ferritin found (in what cells)?
Phagocytes
Hepatocytes
What are small erythrocytes indicative of?
Fe deficiency anemia
What are the two problems when Fe is oxidized in the body?
Fe 3+ is useless
superoxide is created
What is the most damaging ROS?
hydroxide radical
Why is meat a better source of Fe than plants?
In heme and Fe2+ form
How is Fe regulated?
Uptake (there is no loss through urine)
What are the only two ways in which you can lose Fe?
Sloughing off of enterocytes
Blood loss
What percent of the Fe in the body is active?
80%
What is the dynamic storage form of Fe?
Ferritin
What is the degenerated, long-term storage form of Fe?
Hemosiderin
What happens to the Fe in RBCs when the RBCs die?
Taken up by splenic macrophages, added to transferritin, and exchanged with the liver
What is the protein that transports Fe into enterocytes?
DMT1
What is the protein that takes up heme?
Heme carrier protein HCP1
How is non-heme iron (Fe3+) taken up into enterocytes?
First, reduced to Fe2+ by duodenal p4500. Then DMT1 takes it up
The uptake of Fe is not dependent on how much Fe the body has. How, then, do we not have a constant accumulation of Fe in the blood?
Enterocytes can keep the Fe, and it will be lost when the enterocytes are sloughed off
What is the protein channel on the blood side of the enterocytes that allows ferritin to travel out?
Ferroportin 1
What is the kep protein that regulates how much Fe is released into the blood? What organ produces this?
Hepcidin
Produced by the liver if there is too much Fe
How do cell signal that the need Fe?
Transferrin receptor upregulated.
How is Fe brought into cells?
Transferrin binds it, endocytosis, acidification, release
What happens to Fe when it enter the circulation? What about when it enters a cell?
Turns to Fe3+ in the circulatuion
2+ in the cell
What is the protein that acidifies the endosome that contain the tranferrin receptor?
ATPase
What is the protein on the lysosome containing Fe, that allows for Fe to escape into the cell?
DMT1
Inside the cell, Fe is stored as what?
Ferritin
What are the three organs in the body where ferritin is held?
Liver
Spleen
Bone marrow
Ferritin denature into what?
Hemosiderin
Low hepcidin means Fe uptake is low or high?
high
What is the basis for hemochromatosis?
mutations in HFE (Fe upstream regulator) resulting in low hepcidin
What are the two physiologic consequences of hepcidin release?
Low release of Fe by enterocytes
Macrophages do not release Fe into the blood
What is the part of the DNA that regulates Fe? How is this regulated?
Iron response element (IRE)
Iron regulatory proteins bind to the mRNA (that is always there) and prevent transcription.
What are the three proteins that are encoded on the IRE?
Ferritin
delta-ALA synthase
Transferrin receptor
What is the role of delta-ALA synthase?
Produces heme
What is serum Fe used to test for?
Fe poisoning or overload
What is total iron binding capacity used for?
Tests transferrin saturation, which is usually around 30%. Lower = anemia
What complicates the total iron binding capacity values?
Hypoproteinemia
What is the value of the serum ferritin?
Best measure of Fe body stores
What is the value of red cell protoporphyrin?
Fe-free precursor of heme. Elevation = shortage of iron to complete heme synthesis
What cytokine stmulates the production of hepcidin? Why?
IL-6–reduces Fe available to bacteria
What is the first stage of Fe deficiency anemia?
Fe depletion
What is the second stage of Fe deficiency anemia?
Deficient erythropoiesis with normal [Hb]
What is the third and final stage of Fe deficiency anemia?
Hb production is inadequate, resulting in microcytic anemia
What are two iatrogenic causes of Fe overload?
transfusion
Inappropraite parenteral nutrition
Draw the heme synthesis pathway
Draw
What enzyme is the reguatory point for heme synthesis? What is the regulator?
ALA synthase
Heme or Fe will inhibit it
What intermediate of the heme synthesis pathway is susceptible to UV light?
UPG III
Where is ALA synthase located?
Membrane of the mitochondria
What is x-linked sideroblastic anemia?
Defective ALA synthase means not enough heme is produced
What are diseases that involve defects in heme synthesis called?
Porphyrias
What is the problem with how the heme synthesis is regulated, and porphyrias?
Since no heme is produced d/t porphyrias, ALA synthase is upregulated, generating more defective intermediates
What is the most common presentation of a porphyria?
Abdominal pain
What is the effect of EtOH consumption on porphyrias?
induces the synthesis of cytochrome p450s, which require heme
What is acute intermittent porphyria? Symptoms?
Deficiency in porphobilinogen deaminase (PBG deaminase)
Dark red urine
What is porphyria cutanea tarda? Symptoms?
Deficiency of uroporphyrinogen decarboxylase.
Fluorescent urine
Photosentivity of the skin
What are the two enzymes that Pb affects in the heme synthesis pathway?
ALA synthase
Ferrochelatase
Which is the photosensitive porphyria?
PCT since UPG III absorbs UV light
