Iron Flashcards
what is heme
heme iron is a metalloporphyrin ring with Fe in the middle
heme synthesis
glycine + succinyl CoA +(PLP) reason why low Hb can be B6 def
+ (ferrochelatase) to incorporate Fe+2
= heme
Fe absorption depends on
form of iron:
food - heme or non-heme
form of non-heme - ferrous+2 or ferric +3
3 general steps of Fe absorption
- uptake at BBM
- transport across cell
- transport across BLM to plasma
non-heme absorption
- bound nonheme iron is broken down by HCl
- Fe+3 reductase to Fe+2
- Fe+2 uptake by divalent metal transporter 1 (DMT1) into cell
- Fe+2 binds PCBP2 (binding protein) in cell for transport in cytosol, used in cell OR, stored as ferritin
- ferroportin transports iron across BLM. coupled oxidation with hephaestin Cu+-> Cu+2 and Fe+2-> Fe+3
- apotransferrin binds to Fe+3 in blood = transferrin-Fe+3 (transport form in blood)
heme Fe absorption
- Mb and Hb broken down by HCl
- heme uptake into HCP1 (heme carrier protein 1). Free heme absorbed into cell
- heme oxygenase breaks down heme = protoporphyrin + Fe+2
- PCBP2 bound Fe+2
- functional use in cell or stored as ferritin
- ferroportin transports across BLM, coupled with Cu+ -> Cu+2 and hephaestin = Fe+3
- apotransferrin and Fe+3 = transferrin for transport in blood
enhancers of non-heme Fe absorption
vitamin c- reduce Fe+3 to Fe+2
food acids (citrate)
fructose
MFP factor: meat/fish/poultry have actin, mysoin digestive products- has to be contractile proteins, includes shellfish and clams
maybe: CYS-peptide or aa HIS, CYS
mucin: lining of stomach and small intestine (natural chelator unless GI problems/malabsorption)
inhibitors of non-heme absorption
Polyphenols (tannins in coffee, tea)
Oxalic acid (e.g. spinach)
Phytate [prefers Zn2+]
Phosvitin (egg yolk)
Calcium
Fe absorption step 1 (3 parts)
a) heme: released from Hb or Mb
transported across BBM by HCP1 -> inside cell FE+2
b) Fe+2 absorbed by DMT1, inside cell Fe+2
c) Fe+3 either:
i. converted to Fe+2 in lumen
ii. combines w mucin and binds to integrin to be absorbed, when inside cell changed to Fe+2
transport across enterocyte and BLM step 2&3
- Fe+2 transported to BLM by ligands (mobilferrin)
- at BLM, Fe+2 exits through ferroportin
- Fe+2 to Fe+3 conversion so it can combine w transferrin in plasma
- copper enzyme hephaestin needed to couple oxidation
how does liver control Fe absorption
liver protein- hepcidin released when stores are adequate (sensed as diferric transferrin entering liver)
decrease intestinal iron absorption by decreasing ferroportin- bind to ferroportin and degrade
= Fe not released into blood
mutation in hepcidin can prevent control
transport form of iron
Fe+3 bound to apotransferrin = transferrin
receptor for iron
at tissues where iron is used or stored TfR transferrin REceptor binds transferrin and pulls into cell
controlling TfR on membranes = control tissue uptake
what does high TfR in plasma mean
to be excreted, high levels means low iron stores, apotransferrin can be reused
Fe exit from cells that aren’t enterocytes
need Cu enzyme “ferroxidase” to oxidize iron to ferric
enterocyte, hephaestin = other cells, ceruloplasmin
Fe+2 and Cu+2 = Fe+3 and Cu+1
plasma ferritin exiting from stores
ferritin (apoferritin and iron) = cell storage of iron as Fe+3
small but constant leak out of cells, for every 10mg Fe in storage = 1mch/L plasma ferritin Fe
healthy man has 1000mg iron stored = 100mch/L plasma ferritin
women: 500mg = 50mcg/L plasma ferritin
Fe cycling
RBC synthesis: proerythroblasts differentiate into erythrocytes in marrow
-availability of Hb limiting factor in RBC size and number
erythrocytes circulate 120days = functional Fe (not transport)
in reticuloendothelial cells (spleen), old RBCs disassembled, remove Fe - efficient
overall efficient use/reuse of Fe without external losses of blood, adults need to replace 1mg/ day
functional form of Fe
hemoglobin in RBC
what is a measure of Fe storage
plasma ferritin /leakage
1mcg/L = 10mg Fe stored
where is storage of Fe highest
reticuloendothelial cells (spleen)
4 functions of Fe
- Hb and Mb
- each RBC has millions of Hb molecules
- heme synthesis needs glycine, succinyl CoA, PLP, Zn-enzyme, final step: Fe+2 + protoporphyrin ring = heme
- attach globin - cytochromes (contain heme) = ETC
- other heme enzymes (catalase)
- non-heme enzymes
- prolyl hydroxylase in collages synthesis (cross-link) PRO -> OHproline, requires vit C to regenerate Fe+2 in enzyme
non-heme food sources
all plant sources, eggs, dairy, 60% of MFP
enriched flour products or cereals
heme food sources
different meats have diff heme %, average 40%
beef 62%
lamb 57%
pork 49%
poultry 39%
fish and seafood 13%
organ meats 45%
what form of non-heme iron is stable
oxidized, Fe+3
fortified foods use this, Fe+2 might cause peroxidation
supplements: can add Fe+2