Folate, B12 And Haem Flashcards
Explain the biological roles of Fe.
As a component of hemoglobin, Fe enables RBCs to transport O2 from the lungs to tissues, allowing for internal respiration. It also participates in the electron transport chain through cytochromes, facilitating ATP synthesis. Fe is essential for DNA synthesis, as enzymes like ribonucleotide reductase rely on it for nucleotide production, making it essential for cell proliferation, particularly in rapidly dividing cells such as erythroblasts. In the immune system, Fe is necessary for the proper function of immune cells, though it also serves as a resource for microbial pathogens, creating a balance where both deficiency and excess can impact infection susceptibility.
With what substance does free Fe react, making it toxic in cells?
Fe reacts with H2O2 to produce free radicals.
Why is free Fe toxic in circulation?
Fe is toxic in circulation as it supports microbial pathogen growth.
How is non-heme iron solubilized and reduced for absorption?
Gastric acid solubilizes and ionizes non-heme iron, while brush-border ferrireductase reduces it to Fe(II).
How is Fe(II) transported into enterocytes?
Fe(II) is transported via the proton-coupled divalent cation transporter (DCT1) or divalent metal transporter (DMT1/Nramp2), most efficiently in the upper duodenum.
What dietary factors influence Fe(II) absorption?
Organic acids and bile facilitate absorption, while antacids, H2 histamine blockers, and some dietary components inhibit it.
How is inorganic iron transported across the basolateral membrane?
Fe(II) is transported by ferroportin (IREG1) and reoxidized to Fe(III) by hephaestin, a membrane-associated copper oxidase.
How does Fe(III) enter circulation?
Hephaestin promotes Fe(III) binding to transferrin for plasma transport.
How is heme iron absorbed?
It is unclear
What hormone controls iron homeostasis?
Hepcidin regulates iron homeostasis by inhibiting ferroportin, reducing iron absorption and release into circulation.
What is the effect of hepcidin on iron homeostasis?
In low hepcidin conditions, Fe is exported by ferroportin into extracellular space. In high hepcidin conditions, ferroportin is degraded and Fe accumulates intracellularly.
Explain the transport of Fe from enterocytes, through the blood stream, to the target tissue cells.
Iron is transported out of the enterocyte using ferroportin. Fe2+ is oxidised to Fe3+ by hephaestin at the basolateral membrane. Ceruloplasmin (also a Cu-dependent oxidase), may also carry out this oxidation. Fe3+ binds to transferrin, a plasma protein that transports iron in circulation. This complex then binds to transferrin receptors on tissue cells. It is then internalized by receptor-mediated endocytosis. Inside the cell, Fe3+ is released for metabolic processes, including hemoglobin synthesis and storage as ferritin.
Describe the structure of transferrin.
Transferrin has two domains connected by a helical hinge. Each domain has two lobes.
What is total serum iron?
SI is the amount of iron that is actually bound.
What is the total iron binding capacity?
The TIBC is the total transferrin in serum.
Explain the processes of cellular Fe metabolism.
Tf-bound Fe³⁺ enters the cell via transferrin receptor 1 (TfR1) and is internalized into an endosome, where STEAP3 (a ferrireductase) reduces Fe³⁺ to Fe²⁺. The Fe²⁺ is then transported into the cytoplasm via DMT1 (divalent metal transporter 1).
Non-Tf-bound Fe³⁺ is reduced at the plasma membrane by DCYTB (duodenal cytochrome b), assisted by ascorbate, and transported via DMT1/ZIP8/14 into the cytoplasm. The labile iron pool (LIP) represents freely available Fe²⁺, which can be used by mitochondria for heme and Fe-S cluster synthesis, stored in ferritin, or exported via ferroportin (FPN1). This system ensures a balance between iron uptake, storage, utilization, and export, preventing both deficiency and toxicity.
Where do transferrin receptors cluster?
Clathrin-coated pits
How are the 2 sub-units of TfRs linked?
Disulfide bonds
How is Fe recycled through the spleen?
Splenic and hepatic macrophages scavenge senescent erythrocytes and release iron from haem, through hydrolytic enzymes. Haem is catabolized. Movement of iron across the phagosome (similar to endosome) membrane occurs via Dmt1 and Nramp1. Release of iron from splenic macrophage into serum is via ferroportin. Recycling contributes to the major pool of serum, it exceeds contribution of intestinal absorption.
Where is ferritin found?
Ferritin is found in the nucleus, mitochondrion, cytosol and in serum.
What is ferritin responsible for?
Intracellular storage of Fe (sometimes serum)
What could elevated serum ferritin be symptomatic of?
Fe overload, inflammation, leak
Where are H-form apoferritin sub-units found?
In the heart and nucleated blood cells, good for rapid turnover (It can oxidate Fe (II))
Where are L-form apoferritin sub-units found?
In the liver and spleen, good for storage
