Iron Flashcards
Non-heme Iron
Transported by DMT1 (reduced). Vit C enhances absorption.
Found only in plants.
Primarily bound to phytates, making it unavailable for absorption.
Need to eat twice as much non-heme iron to compensate for lack of bioavailability.
Heme Iron Digestion
Gastric and intestinal proteases hydrolyze heme iron from the globin portion of hemoglobin and myoglobin.
hcp1(heme carrier protein) accepts heme into enterocyte
Gastric and Intestinal Proteases
Hydrolyze heme iron from the globin portion of hemoglobin and myoglobin.
Heme is carried across brush border of the enterocyte via hcp1 (heme carrier protein 1).
hcp1
Heme carrier protein 1.
Located in small intestine, it carries heme to an enterocyte.
Non-heme Iron Digestion
Hydrolyzed by HCl and proteases.
Stomach acid reduces Fe3+ (ferric ion).
Ferric iron passes from stomach to alkaline small intestine which creates insoluble ferric hydroxide.
Fe(OH)3
Or vitamin C can reduce ferric to ferrous iron which can be transported via DMT1.
DMT1
Transports ferrous iron.
Inversely regulated by iron status.
Integrin
Questionable ferric iron transporter.
Chelators and Ligands
Compounds that bind to form a complex.
Influences iron absorption both ways:
Loose, soluble complex = + absorption
Strong, insoluble complex = - absorption
Enhancers of Nonheme Iron Absorption
Sugars (fructose, sorbitol)
Acids (ascorbic, citrate, lactic, tartaric)
Meats and their digestive products
Mucin (vitamin A)
Inhibitors of Nonheme Iron Absorption
Polyphenols (tannins in tea and coffee)
Oxalis acid
Phytates
Ca, Zn, Mn, Ca, Zn, Cu
Entering Enterocyte (Chaperones)
First step in absorption. Binds to iron.
Ferric Iron: AA (cysteine and histidine), Mobilferrin
Ferrous Iron: Ferritin, Hemosiderin
Ferritin (storage)
Most iron is stored in ferritin, mainly in the liver.
Ferritin production is regulated by iron status.
Must be in oxidized (+3) form; 4,500 atoms stored.
Serum ferritin used to evaluate iron status.
Transferrin (transfer)
Glycoprotein synthesized in liver, found in blood
Transfers iron within blood stream.
Only carries 2 oxidized iron (ferric) atoms.
Contains 33% of body’s iron.
Iron ^ = less transferrin
Siderophores
Bacteria binding protein.
Compete with transferrin for iron.
Infection.
Hepcidin (regulator)
Released from liver when iron stores are high.
Regulation based on transferrin.
Decreases ferroportin.
Liver detects iron status by binding of diferric transferrin to TfR1.
HFe is released, and binds to TfR2.
HFe-TfR2 complex senses iron status. Stimulates hepcidin synthesis.
Hepcidin targets enterocytes and macrophages. Degrades ferroportin which prevents iron from being exported into blood.
Hemochromatosis
Mutation that interferes with hepcidin release, thus causing excess iron storage.
Adult men and postmenopausal women who are not iron deficienct should not supplement.
RDA and UL
8mg men 18mg women
45 mg constipation, nausea, vomiting.
Increase risk for stomach cancer and CVD
Inhibitors
Calcium and zinc
Deficiency of copper or vitamin A
Polyphenols, phytates, oxalic acid, fiber, tannins
High pH
Enhancers
vitamin C, riboflavin, niacin, mucin (vit A), sugars, protein
Low pH
Heme Iron
Porphyrin ring. Derived from hemoglobin and myoglobin.
20% absorption
TfR
Transferrin receptors.
Endocytosis takes up transferrin, iron atoms then released.
Toxicity 45 mg
Inhibits zinc absorption.
Increases risk for stomach cancer and CVD.
Constipation, nausea, vomiting.
Death @ 200 mg.
Hemochromatosis
Genetic disorder.
Down regulates iron absorption, excess iron is stored. Organ damage.
How is iron excreted?
Can only be taken out via blood giving.
Mucosal cell sloughing. No purposeful excretion.
Why is it important for iron to be bound to something?
Ability to oxidize creates free radicals. DNA damage (cancer).
Iron can be used by bacteria to proliferate, especially if protein deficient.
Copper
Oxidizes iron to bind to transferrin to be transported through the blood stream.
Ceruloplasmin and Hephaestin
Cu dependent enzyme that oxidizes iron to ferric (+3) form.
What vitamins can reduce iron?
Vitamin C, niacin, and riboflavin.
Take iron off ferritin.
Assessment
Serum ferritin
Hemosiderin
Found in many cells (primarily liver). Aggregates of ferritin.
Iron binding proteins
Hemosiderin Ferritin Transferrin Siderophores Amino acids Mobilferrin
Mobilferrin
Enterocytes. Transports iron through cells.
Hemoglobin and myoglobin
Functional Fe
65% oxygen in blood
10% oxygen in muscles
Most iron present here.
Recycling
Iron stored in macrophages in cell Ferroportin Ceruloplasm Transferrin TfR (transferrin receptor that accepts Fe)
Hypochromic microsytic anemia
Not enough hemoglobin makes small, pale red blood cells. B6 or iron deficiency.
Measure ferritin.
Sources
Heme: beef, animal products, some in milk
20% absorption
Non-heme: beans, raisins, nuts
2-8% absorption
Ferroportin
Gets iron out of enterocyte.
Fe can be sloughed off here if down regulated.
Functions: Heme Moiety and Cofactor
Hemoglobin/ myoglobin: oxygen transport in blood/ muscle cells
Cytochrome: transport electrons
Oxygenases: insert oxygen into substrates
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Cofactor for many enzymes (peroxidase and oxidoreductase)
DNA synthesis
Cytochromes
Transport electrons via reduction/ oxidation.
Respiratory system.
