lecture 20: iron Flashcards
factors that affect iron bioavailability
interactions with ligands
organic acids enhance absorption
inhibitory ligands: phytates, polyphenols, calcium, fiber
mechanisms of iron exchange, transport, and storage must maintain…
an extremely low free iron concentration (can generate highly cytotoxic free radicals)
storage forms of iron
ferritin and hemosiderin
ferritin structure
H subunits: ferroxidase activity (Fe2+ to Fe3+), limits Fe2+ induced production of hydroxyl radicals
L subunits: nucleation of iron core of ferritin
liver and spleen (iron storage): higher proportion of L subunit
heart and brain (iron detox): H subunits predominant
transferrin
transport of iron, facilitates iron uptake
synthesized in liver
two-iron binding sites, tight Fe3+ binding
transferrin receptors
involved in cellular uptake of transferrin bound-iron from circulation, high affinity for Fe3+
iron (Fe2+) export
occurs via ferroportin, works with ferroxidases to export iron out of the cell
dependent on transferrin and ferroportin
transferrin-bound uptake by cells
mediated by expression of transferrin receptors
transferrin binds > complex is invaginated into clathrin-coated pits to form vesicles
Fe3+ reduced to Fe2+
ferroportin
export of Fe2+ (ferrous iron)
works with ferroxidases to oxidize to Fe3+ before loading to apotransferrin
DcytB
membrane bound, reduces Fe3+ to Fe2+
DMT1
absorbs iron from GI tract after reduction to Fe2+
uptake of luminal heme iron into enterocytes
heme iron more bioavailable than non-heme
after absorption, degraded by heme oxygenase resulting in free Fe2+
erythroblasts
nucleated developing RBCs, eventually becomes erythrocyte (mature RBC)
takes up transferrin-bound iron and transported into mitochondria to form heme
biological functions of iron
exists in several oxidation sates
transport/metabolism of oxygen
movement of electrons
iron proteins can be classified according to the coordination chemistry of their iron
heme proteins, iron sulfur proteins, non heme non iron sulfur protiens
heme proteins
single iron bound by heme
O2 transport, e transfer, cyt P450 metabolism
oxygen carriers hemoglobin and myoglobin
unoccupied 6th coordination site- binding site for O2, inorganic ligands, organic ligands
AA 6th site - e transfer
6th coordinate position of heme in electron transporting cytochromes
6th coordinate position occupied by an AA residue
cytochromes transport electrons, alternate iron in heme between Fe3+ and 2+
iron-sulfur cluster proteins
most common: 2Fe-2S and 4Fe-4S
electron transfer rxns, initiating catalysis, biological sensors
mononucleur non-heme iron proteins
single Fe atom, involved in rxns with O2 as substrate
1st subgroup: aromatic AA hydroxylase
2nd subgroup: dioxygenases, requires keto acid substrate
one O2 transferred to substrate, other to keto-acid
dinuclear non-heme iron proteins
dinuclear iron sites
involved in Fe2+ to Fe3+ oxidation
iron deficiency
low hemoglobin conc > anemia
more anemic in underdeveloped/developing regions: less meat, more food that blocks iron absorption - PHYTATES
exacerbated by infectious diseases
