IRON Flashcards
States of fe
ferrous- 2+ acidic
ferric 3+ neutral/alkaline
some of the dangerous effects of iron
Can cause ROS because it reduces o2 and can also binf to various macromolecules changing the structutre so we have iron binding proteins to prevent the deleterious effects of fe
what is heme
fe 2+ and protopoprhyrin 4
heme containing proteins
transfer of o2-Hb
storage of o2 -myoglobin
enzyme catalysis- No synthase, prostgalndin synthase (COX) Catalase
non heme iron containing proteins
F-S proteins in the oxidative phosphorolation ETC
Iron transport protein -transferrin
Iron storage -ferratin
Heme iron pathway
2+
released in enteroctytes , can be stored there in in ferritin or transported into blood by IREG 1 . The fe2+ is oxidised by ceruloplasmin which is a ferroxidase enzyme mainly used for cu transport.
fe in the blood is bound to to transferrin (fe3+) and goes to liver which is the main site of storage
free iron
3+ reduced to 2+ in the intestines - vitamin c helps in non heme iron absorption
then DMT 1 (which transports all ions )
hepcidin
25 aa polypeptide. REGULATION OF FE IN PLASMA MAIN FUNCTION. Made by hepatocytes, recently its synthesis was found in bacteria, activated neutrophils and macrophages. Is increased by IL - 6 pro-inflmmatory cytokine inhibits fe transport by binding to to the fe export channel ferroportin causing its internalisation and lysosomal degradation . low levels of fe= low hepcidin
what is the form of iron in the liver
bound to ferritin so 3+
ferritin
24 subunits of H-L chains and can store about 4,500 fe3+
where is the majority of stored fe found
liver, RES, skelteal muscle
transferrin
can bind several metals but has the highest affinity for fe3+ . ferrous does not bind. transferrin binds 2 moles of fe3-
how is excess iorn stored
the excess fe deposits next to the ferritin-iron complex known as hemosiderin
what happens afte fe is bound to tranferrin
transferrin carried fe to the cells where there is an internalisation of the iron -transferrin receptor , receptor medicated endocytosis forming a vesicle inside the cell. now you have to release the iron and this works by an acidic environment (lysosomes) iron gets released
how do we loose iron
sweat, feces, sloughed of cells ,bleeding
how do we measure iron stores
small amounts of ferritin enter blood and can be used to measure the adequecy of iron stores.
Clinical aspects
excess fe is bad cos hemosiderin can cause cell damage
decreased fe is bad cos less o2
hemochromatosis: basically and iron overload, caused by deposition of hemosiderin in tissues. there is too much iron being absorbed so it gets stored in organs such as
liver
Clinical aspects
excess fe is bad cos hemosiderin can cause cell damage
decreased fe is bad cos less o2
hemochromatosis: basically and iron overload, caused by deposition of hemosiderin in tissues. there is too much iron being absorbed so it gets stored in organs such as
liver- cirrhosis
pamcrease- diabtetes
skin and organs -bronze pigmentation
IRON definciency anemia : characterised by small (microcytic) and hypochromic (low pigment) RBC . Caused by reduced iron uptake and or excess iron excretion. most common causes of GIT bleeding or excess flow
ferroportin
some cells such as the liver macrophages enetrocytes can EXPORT fe by ferroportinFerroportin is assisted by a ferroxidase
(hephaestin in enterocytes and ceruloplasmin in
macrophages) to deliver FERRIC iron to transferrin
where is heme made
heme can be synthesised by almost all the tissues of body but the main one Liver and bone marrow. liver its rate of synthesis varies but bone marrow is relatively constant
synthesis of heme
- succinyl COA + glycine= ALA
- 2xALA ( ALA dehydratase) - porphobilinogen
- 4 porphobilinogens condense to form a linear chain HMB
- cyclises spontaneously to form uroporphyrinogen 1 or its converted to uroporphyrinogen 3 by enzyme uroporphyrinogen 3 co synthase.
synthesis of heme
- succinyl COA + glycine= ALA
- 2xALA ( ALA dehydratase) - porphobilinogen
- 4 porphobilinogens condense to form a linear chain HMB (HMB synthase)
- cyclises spontaneously to form uroporphyrinogen 1 or its converted to uroporphyrinogen 3 by enzyme uroporphyrinogen 3 co synthase.
- uroporhyrinogen 3/1 is decarboxylated to COPROpopryphrinogen
- copro enters mitochondria and gets converted to protoporphyrinogen 3 by
coproporphyrinogen oxidase - protoporphyrinogen 3 is converted to protoporpyhrin by enzyme protoporphyrinogen oxidase
- final step ferrochelatase (heme synthase)
side chains of uroporphyrinogen
acetyl and propinoyl groups
where does heme synthesis occur
like the urea cycle partly in the mitochondria then cytosol. starts of in the mitochondria. only the first step (formation of ALA) occurs in mitochondria. Then moves to cytoplasm, then . moves back to mitochondira again.
