Iron Flashcards
Iron is required for 3 systems of metabolic processes
- haemoglobin
- myoglobbin
- cytochrome
Transport of iron
- transferrin
- complex on protein ( ferritin. haemosidirin)
- iron-sulfure clusters (enz)
- litte in free form bc toxic to proteins, membranes, DNA
iron storage around body
- haemoglobin (50%)
- ferritin (30%) in liver, BM, Reticulo-endoth. cells
- myoglobin (7%)
- cytochromes (7%)
Regulation of iron homeostasis (9)
- Fe3+ reduced to Fe2+ by duodenal cytochrome b (Dcytb)
- Divalent metal transporter (DMT1) allows entery of Fe2+ through enterocyte (If Fe3+ bound to ferritin then reduced to Fe2+)
- Fe2+ Exit enterocyte via Ferroportin
- Fe2+ oxidised to Fe3+ by Hephaestin-a ferro oxidase
- 1-2x Fe3+ binds to Transferrin to be transported in blood to liver
- Transferrin binds to TrF2 -> displaces HFE
- HFE binds to HJV
BMP6 secretion - activates formation of hepcidin
- hepcidin bind to ferroportin = dec Fe absorption
function of caeruloplasmin
- responsible for Fe release in iron stores in liver & other cells, converting Fe2+ to Fe3+ (like hephaestin in enterocyte)
- Iron recycling
- copper transport
What are the pathophysiological processes involved in iron deficiency of chronic disease
Due to Acute/chronic infection or inflamm. disorder = IL6
=> stimulate process to make hepcidin = Hi hepcidin = dec Fe absorption
- Transferrin may be low
- Ferritin N/inc
What are the pathophysiological processes involved in iron overload caused by alcohol * also applyies to acute/chronic liver disease
- blocks the iron sensing in liver = process to making hepcidin is ceased/dec
- low hepcidin = hi Fe absorbption
What are the pathophysiological processes involved in ineffective erythropoeisis = dec tiss. O2 from thalassemia & sickle cell
- dec O2 = hypoxia inducible factor (HIF)
- HIF release EPO (& duodenal DMT1)
- EPO -> Erythroblast make ERFE -> bind to & inhibit Bmp6 ≠ production process of hepcidin
biochemical measurements for Ix
iron, Transferrin, ferrritin, transferring saturatino (%Tsat)
tests & measurements for iron deficiency
- dec Fe, inc transferrin => dec %Tsat
1. inc Serum / soluble transferrin receptor
2. Iron stain (prussian blue) of BM aspirate *Gold std
tests & measurement for iron overload
*inc Fe, dec transferrin => inc %Tsat
1. Genetic studies for haemochromatosis mutations
2. hepatic iron indices: tiss. biopsya-, magnetic resonance imaging
Regulation of ferritin levels (at translational level)
@ Low iron [ ] = not enough to bind to regulatory site on IRE-binding protein = remain activated = bound to Iron-response element (IRE) on 5’ of ferritin mRNA = ribosome can’t attach to IRE ≠ translation
*iron acts as regulatory inhibitor to IREBP = translation of ferritin
Ferritin is a marker for Fe stores but Why is ferritin not a reliable indicator for overload? what is used more as a reliable source?
a) - also a acute phase protein
- inc in liver damage, inflammation, acute illness, injury, surgery
b) transferritin saturation - Sp for Fe overload
Regulation of transferrin receptors levels (at translational level)
@ low iron [ ] = not enough to bind to regulatory site on IRE-binding protein = remain activated = bound to Iron-response element (IRE) on 3’ of transferritin mRNA = protects transferrin receptor mRNA from degradative nucleases & allows translation of transferrin receptor = to bring more iron in
*Hi iron [ ] = degrade tranferrin mRNA = stop Fe brought in
Compare the clinical significance of the HFE C282Y homozyg. and H63D mutations
HFE C282Y: Inadequate or inappropriate hepcidin secretion, or effect, = iron overload disorders. (but at low penetrance so not affect magority)
H63D: iron over load but lesser extent than C282Y
C282Y/H63D: compound heterozygotes: disrupt S-S in alpha 3 domain = not bind to beta 2 microglobulin. low iron status?
