1. How does iron status regulate iron absorption?- Iron balance is controlled at point of absorption- Absorption adapts to a person’s needs - Mucosal cells in the intestine store excess iron in mucosal ferritin (a storage protein)- If the body needs iron: mucosal ferritin releases iron to mucosal transferrin (a transport protein), which hands off iron to another transferrin that travelsthrough the blood to the rest of the body- If the body does not need iron: Hepcidin (a hormone released from the liver) tells the digestive system to reduce the absorption of iron. Thus, iron is not absorbed and is excreted in shed intestinal cells instead. Iron absorption is therefore reduced when the body does not need iron. - Hepcidin maintains iron levels in the body. Hepcidin prevents hemochromatosis (excess iron in the body)2. How does heme iron absorption compare to non-heme iron absorption? For the non-heme iron, what form is better absorbed? - Heme iron (from hemoglobin) is better absorbed (23%) than non-heme iron (from plant foods and animal foods)- Non-heme iron must be reduced from Fe^3+ (ferric) to Fe^2+ (vitamin C needed and ferrireductase) - Non-heme iron (once reduced to Fe^2+) goes through DMT-1 - Heme iron goes through the heme transporter (HCP1)- Non-heme iron is hard for our body to transport- Fe^3+ (non-heme iron) is soluble in acid/insoluble in alkaline solution  less absorbed3. Identify the enhancers and inhibitors of iron absorption. - Non-heme iron absorption-enhancing factors:o Meat, fish poultry (MFP factor) o Ascorbic acid (vitamin C- sugars, acids)  Reduces non-heme iron from Fe^3+ to Fe^2+ (Fe^2+ can be absorbed better)o Ferrireductase at brush border o Low iron status- Non-heme iron absorption inhibitors:o Phytates and fiberso Calcium and phosphorous (at high intakes)o EDTA in food additiveso Tannic acido Polyphenols (tea & coffee) o Oxalates (spinach)o Phosvitin o Divalent cations o Excess alkalinization o Malabsorption syndromes o Rapid transit time4. How do Zn and Fe influence each other’s absorption? - High Zinc causes low copper and iron absorption because:o Copper binds to metallothionein (trapped)o Zinc binds with transferrin= decreases iron absorption- High iron intake causes low zinc absorption5. What’s the function of metallothionein in zinc homeostasis?- Metallothionein is a zinc storage protein (for iron it is mucosal ferritin)- It is a zinc binding protein- Regulates Zinc absorption - Releases zinc into the blood when needed 6. What protein transfers iron in the blood? What form of iron does it bind to? How is iron transported in the way taken up by cells? - Mucosal transferrin transfers iron to blood transferrin - Blood transferrin carries iron in the blood to the rest of the body - Fe^3+ is the form of iron on transferrin - Iron is taken up by the cells when it is bound to transferrin (holoenzyme)7. What protein stores iron inside of the cells?- Ferritin - Homosiderin- Storage in the bone marrow, spleen, and liver8. How does iron status regulate the amount of the two proteins above? By what mechanisms? Note: This regulation is a good example of a nutrient regulating gene expression at the mRNA level as opposed to at the transcriptional level like vitamin D and A do. - If you have low iron:o Iron response element binding protein (3 Fe) binds to IRE on ferritin mRNA and inhibits translation of ferritino IRE-BP (3 Fe) binds to transferrin receptor mRNA and increases the stability of the mRNA.- If you have iron:o IRE-BP binds an additional Fe ion. IRE-BP9(4 Fe) translocates into themitochondria to function as aconitase in the TCA cycle. ANo INTERACTION WITH mRNA WILL NOT OCCUR WHEN IRON IS HIGH.ADDITIONAL QUESTION: What organs store iron in the body?- In red blood cells as heme in hemoglobin - Storage iron mainly in the bone marrow, spleen, and liver - Myoglobin9. What are the commonly used methods to determine iron status? - Iron deficiency can be assessed by measuring various biochemical indices:o Measure serum ferritin and transferrin  Ferritin is reduced (storage) and transferrin is increased o Measure transferrin saturationo Measure erythrocyte polyporphyrin A precursor to hemoglobin that accumulates in plasmao Measure hemoglobin and hematocrit (volume of RBC) values 10. Generally, what are the functions of iron in the body? What are the functions of zinc in the body?- Iron Functionso Oxidation- reduction reactions of energy metabolism Cofactor to enzymes Part of the electron carriers in the ETCo Structural/functional component of Hemoglobin (blood) and myoglobin (muscle) Most of the body’s iron is found here  Carries oxygen  Accept, carry, and release oxidationo Cofactor in enzymes that control: brain function, tissue formation, immune function, hormone production - Zinc functionso Catalytic role in enzymes  Zinc metalloenzymes- Aid in synthesis of DNA and RNA- Manufacture heme for hemoglobin- Participate in essential fatty acid metabolism- Release vitamin A from liver stores- Metabolize alcohol in the liver- Dispose damaging free radicals (ANTIOXIDANT) Zinc is needed for action of several hormones- insulin and thyroid gland  Zinc is essential for cell division Zinc affects blood clotting  Zinc is required for normal taste perception Zinc is required for normal sperm development and fetal development ADDITIONAL QUESTION: What are metalloenzymes?- Metalloenzymes are enzymes that contain one or more minerals as part of their structure - This is an enzyme containing tightly bound metal atoms (e.g. the cytochromes)11. What are the major causes of iron deficiency? - Iron is the most common mineral deficiency in the world - Results from depleted tissue stores- Occurs when iron absorption cannot keep pace over an extended period of time with the rate of iron loss- Initially: ferritin levels decrease & transferrin increases to help facilitate absorption- Increase in drug abuse increase in iron deficiency- Primary causes: low intake of bioavailable iron, increase iron requirements (rapid growth, pregnancy, menstruation), excess blood loss (pathologic infestations, unsanitary conditions)12. List a few main symptoms of iron deficiency. o Reduced iron stores compromise energy metabolismo Tired tissueso Impairment of neurotransmitter synthesis o Reduction in physical and mental work- Iron deficiency with anemiao Severe depletion of Fe storeso Low hemoglobin concentrationso Microcytic, hypochromic (no