Learning Objectives 1) Identify the physiological roles for iron and the importance of oxidation states for its function - Healthy adult has 3-4 g of iron: 65% bound in heme prosthetic group of hemoglobin, 10% in myoglobin, 1-5% in other heme-containing enzymes, rest of it in non-heme iron (transferrrin in blood and ferritin in cells)!- Iron exists in body in 2 oxidation states: Ferric (Fe3+) and Ferrous (Fe2+), can switch between these two by accepting or donating an electron (Fe3+ + electron- <--> Fe2+)!- Fenton Reaction!- Generates a hydroxyl w/a free radical that can damage proteins, DNA, and lipids (by reacting w/them) and Fe2+ is more likely to undergo this rxn!!- Excess iron in blood is sequestered in transferrin and in cells is bound to ferritin!- Tests to monitor iron status:!- Serum iron: total circulating iron in serum!- Total iron binding capacity: total amout of transferrin!- Percent transferrin saturdation: how much of total transferrin is bound to iron!- Serum ferritin: total amount of iron stored in the body!- Ferritin: 24 subunits that form a cage that can hold up to 4500 Fe3+ molecules, found in every cell type in body!- one of subunits has: ferroxidase activity so it can convert Fe2+ to Fe3+ (safer storage form)!- syn. is regulated by iron levels!- Transferrin: carrier protein that binds Fe3+ iron in the plasma, taken up by cells by interacting w/ transferrin receptor (TfR), this complex is internalized by endocytosis-->forms endosomes-->fe3+ released in endosome-->TfR recycled to pm!- syn. is regulated by cellular iron levels! 2) Understand the pathways for intestinal iron absorption and transport and for cellular uptake of iron 3) Describe how iron absorption and cellular iron levels are regulated to achieve iron homeostasis - Iron normally lost thru shedding intestinal and skin cells and blood loss, so the regulation of iron homeostasis occurs entirely at the level of intestinal absorption and mobilization from body iron stores (liver, macrophages)!- Iron absorption varies from about 5-10% in healthy people up to 20-35% in an individ who is irondeficient - Hepcidin secreted in response to high iron levels-->binds to ferroportin-->triggers its internalization and degradation!!!!!!!!!!!- Individ cells control Fe availability by controlling synthesis of ferritin and transferrin receptor!- Regulator: Iron Regulatory Protein (binds iron)!- IRP1= a non-heme iron protein functions as metabolize enzyme (aconitase) inv. in citric acid cycle (when iron is high)!- When iron is low: it loses iron, is inactive, and becomes an RNA-binding protein that recog the IRE (Iron response element) in ferritin and transferrin receptor mRNAs!!! 4) Recognize how excesses and deficiencies in iron lead to conditions of hemochromatosis and iron-deficiency anemia - Hemochromatosis: a genetic disease of iron overload, patients develop toxic iron deposits in liver, heart, and other organs leading to cirrhosis, cardiomyopathy, diabetes, and other endocrine disorders!- Treatment: regualr phlebotomy!- Absorb about 30% of dietary iron (vs. normal individial 10%)!- Most common genetic disorder in the world (carrier frequency 1/8-1/12) (1/200-1/300 people)!- Common form: caused by a mutation in the HFR gene that reg hepcidin induction in response to high iron --> insufficient hepcidin + enhanced iron absorption!- Iron-deficiency anemia - Most common form of anemia in the world, = 1 billion people, more in women!- Most common cause: parasitic infections --> intestinal blood loss!- Best known symptom: microcytic hypochromic anemia-- you have small and pale red cells due to decreased hemoglobin!- Often causes decreased immunocompetence!- Iron Nutrition - Elevated req during puberty and pregnancy and in menstruating women!- Men consume 17mg/day (above RDA), women consume 12 mg/day (below RDA)!- Good sources: red meat, beans, spinach, poultry, fish, oysters, liver!- Non-heme iron absorbed less effectively than heme iron (from animal sources)
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