Iron Metabolism Flashcards
Oxygen can react with (blank) in one electron red-ox reactions.
iron
Oxygen transport and storage are done via what two things?
myoglobin and hemoglobin
Where do you find iron-containing proteins?
amino acid metabolism
inflammatory responses
Electron transport -cytochromes
Iron and O2 generate (blank). There are many mechanisms in place to avoid excessive production of these.
free radicals
(blank) is sequestered by binding proteins, protoporphyrins, and Fe-S centers
Iron
Where do infants get iron from?
lactoferrin in mothers milk
Where do you get absorption of iron?
upper small intestine (mostly duodenum)
Heme-iron is taken up by a heme transporter (HT) protein. Once in cell, heme (blank) splits iron from heme
dioxygenase
(blank) promotes Fe+2 to Fe+3
Fe+3 is reduced to Fe+2 by a ferric reductase: duodenal cytochrome b (Dcytb).
Gut environment
What is the absorption of Iron in the gut?
Fe+2 then transported by DMT1 across apical membrane of enterocyte as Fe+2.
Ferroportin (FP) aided by hephaestin (Hp)(redox protein) makes the Fe2+ into Fe 3+ and transports it into the interstitial fluid then to plasma
Plasma Fe+3 binds to apo-transferrin to form transferrin
Some Fe+2 is stored as Fe+3-ferritin in cell
What is the major storage protein of iron?
ferritin (4500 irons Fe3+ to one protein molecule)
When do you see the aggregated form of ferritin?
in iron overload where it is hemosiderin (partially degraded)
(blank) level is the most convenient laboratory test to estimate iron stores
Under steady state conditions, the serum ferritin level correlates with total body iron stores
serum ferritin
Iron (III) is (blank) at physio pH, this is why transferrin is need to by Iron III to avoid precipitation in plasma
insoluble
Is it healthy to have low conc. of free iron?
no it is damaging
Essentially all plasma iron is bound to (blank). How many irons does this carry?
transferrin
2 Fe 3+
What is the normal saturation % of transferrin with iron?
33%
Describe iron uptake into the cell
transferrin bind iron-> transferrin iron complex binds to transferrin receptors (Tfr). the Tfr-diferric(2 irons)-Transferrin complex then gets sucked into an endosome and brough into the cell-> endosome becomes acidic and iron is released from complex-> iron is taken by mitochondria and put into heme by ferrochetolase-> apotransferrin is recycled back to plasma to get more iron.
What is the primary storage site of iron?
liver
What is the master control organ of iron homeostasis and produces the peptide hormone hepcidin?
liver
What does hepicidin do?
What is the production of this stimulated by?
Inhibitor of processes that put iron into the blood
Directly interacts with ferroportin
Production is stimulated in:
Inflammation
Iron overload
(blank) controls the main inflows of iron into plasma.
hepcidin binds directly to (blank) which is the hepcidin receptor.
hepcidin
ferroporFtin
What happens when hepcidin is high?
hepcidin is internalized away from membrane, iron is trapped in enterocytes, macrophages, and hepatocytes, level of circulating iron goes down
(iron uptake is high)
What happens when hepcidin is low?
iron enters plasma at high rates (iron uptake is low)
What is the major site of iron absorption in the small intestine?
the duodenum
What happens in each of these cells: villus cell or duodenal epithelial cell? liver parenchymal cell? reticuloendothelial macrophages? red blood cell precursor?
dietary iron absoprtion
iron storage
iron recycle
heme synthesis
Lots of ferritin is not needed in the face of low iron stores because ferritin is an (blank) storage protein.
intracellular
Extracellular iron concentration is sensed through the interaction of (blank) with (blank). If you have a lot of iron what will be made?
holotrasnferrin and TFRI/TFR2 (transferrin receptors)
ferritin and hepcidin
(blank) is the Inappropriate increase in intestinal iron absorption resulting in deposition of excessive amounts of iron in parenchymal cells with eventual tissue damage and impaired function of organs.
hemochromatosis
You get (blank) when you have saturation of iron-binding proteins
hemochromatosis
What does this describe? Deposition of hemosiderin in the tissues (aggregated ferritin) Primary affected tissues Liver - cirrhosis Pancreas - diabetes Skin – bronze; bronze diabete
hemochromatosis
What are these primary causes of:
Autosomal recessive allele
Locus designated HFE
Major histocompatibility complex (MHC) class-1 gene.
Protein associates with b2-microglobulin.
hemochromatosis
What is the mechanism of hemochromatosis/
messed up HFE/transferrin interaction resulting in increased uptake of iron
What is the primary cause of hemochromatosis?
genetics
Iron overload is reflected in serum (blank) concentrations
ferritin
serum ferritin contains (blank) iron but tissue ferritin contain (blank) iron. HOw is it measured?
little to none
A LOT of
ug/L
What happens to your serum ferritin levels as you age?
it increases
What is the most common cause of poisoning of young children? What is the treatment?
iron poisoning (too many flinstones vitamins
strong laxative,
IV deferoxamine mesylate (Desferal)
-Binds iron and excreted in urine
What is this:
Serum free iron not bound to transferrin
Lipid peroxidation occurs, resulting in damage to blood vessels and Mitochondria
iron toxicity
The most common cause of anemia is (blank)
iron deficiency
In most adults, iron deficiency results from (blank)
blood loss (~5% of premenopausal women in US)
Most functional defects in iron deficiency occur with the development of what three things?
+
anemia
Weakness and pallor
Exercise intolerance
Women who donate blood will develop (blank) more often than men
iron deficiency
