Iron Metabolism Flashcards
What is the reticuloendothelial system or macrophages?
Reticuloendothelial system: total combination of monocytes, mobile macrophages, fixed tissue macrophages, and some specialized endothelial cells in the bone marrow/spleen/lymph nodes. Almost all of these cells result from monocytic stem cells.
Generalized phagocytic system located in all tissues, especially in the tissue areas where large quantities of particles, toxins, unwanted substances must be destroyed.
Reticular tissue has collagen in fibres forming a network that supports cells. Produced by fibroblasts. Provides a framework and environment for cells in hematopoietic tissue, some lymphoid organs (BM, lymph nodes, spleen). Macrophages and dendritic cells are dispersed in reticular tissues, monitor cells formed there or passing through.
Why is iron damaging to cells
Iron can donate electrons to O2, forming O2-, a reactive superoxide radical, or to hydrogen peroxide –> OH radical.
These molecules can oxidize macromolecules like lipids, proteins, DNA –> consequences to cell
How much iron is in the body total?
3-4 g in various forms
How much iron lost per day? How?
Lost via shedding of cells from skin, gut (epithelial cell turnover) and bleeding. 1-2 mg iron per day ( < 0.1% of total body iron)
How much iron do RBCs carry?
2 - 2.5 g (majority of the body’s iron)
How much iron is in the plasma? What is it bound to?
2 - 3 mg, bound to transferrin (transports iron for use in erythropoiesis in BM)
What form is iron stored in, and what protein does this?
Iron is stored in the ferric (Fe3+) form, in ferritin. Part of the ferritin protein has ferroxidase activity - converts F2+ to Fe3+.
How much iron is stored? Where is it primary kept?
About 1 gram (in males) of iron is stored mainly in hepatocytes andl liver macrophages (also spleen red pulp macrophages)
Women of reproductive usually have significantly less stored iron (d/t menstruation, childbearing)
Where does iron absorption take place in the gut?
Duodenum and upper jejunum
How is dietary non-heme iron absorbed?
Initially in ferric form (Fe3+), reduced in the gut to ferrous (Fe2+) by ferric reductase.
Fe2+ is transported into enterocyte by divalent metal ion transporter 1 (DMT-1). Some stored, some released.
How does iron leave the cell?
Ferroportin. Found on basolateral membrane of enterocytes, reticuloendothelial macrophages, hepatocytes.
Ferroportin exports iron in the ferrous (Fe2+) form. Transferrin binds it in the Ferric Fe3+ form Ferroxidases play a role in iron transport
What determines ferroportin activity?
- Ferroportin is regulated transcriptionally in enterocytes, macrophages, and translationally by iron responsive element (IRE) in its mRNA via iron regulatory proteins (IRPs)
- Low intracellular iron –> IRPs bind to IRE in ferroportin mRNA –> translational suppression, less iron export
- Hepcidin also regulates it post-translationally
What does hepcidin regulate?
- Absorption of iron by enterocytes
- efflux of recycled iron from macrophages
- efflux of stored iron by hepatocytes
Where is hepcidin produced?
Mainly in hepatocytes
How does hepcidin regulate iron levels?
Excess iron in plasma –> liver secretes hepcidin –> hepcidin binds ferroportin –> endocytosis and degradation of both –> iron is locked in cell.
Also regulates intake of iron in duodenal entrocytes (mechanism unclear as iron absorption on apical surface, ferroportin on basolateral surface.) May be via rising intracellular iron levels d/t reduced efflux from hepcidin and ferroportin.
