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Iron

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Intro to Iron

  • A metal element that exists in several oxidation states ranging from Fe6+ to Fe2+

  • most important forms: ​

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  • stable in blood and foods​

  • RDA

    • men: 8mg​

    • women

      • premenopausal: 18mg​

      • postmenopausal: 8mg

      • pregnant: 27mg

      • lactating: 9mg

  • UL = 40mg

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Iron Food Sources

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  • heme iron

    • from hemoglobin and myoglobin in animal products: meat, fish, poultry (MFP)​

  • non heme iron

    • nuts, fruits, vegetables, fortified grains, tofu, dairy​

study question:

  • what are vegetarians and vegans at risk of?

Digestion and Absorption

Heme Iron

  • heme iron must be hydrolyzed from the globin portion of hemoglobin/myoglobin before absorption

  • enzymes include proteases in the stomach and small intestines

  • heme is soluble and can be absorbed as a whole

  • heme carrier protein 1 (hcp 1) is used for transport

  • absorption most efficient in duodenum

Non heme Iron - bound to food components

  • must be released before it is absorbed

  • released with help from HCl and proteases from stomach and small intestines

  • mostly ferric iron released, some ferrous

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  • Fe3+ is fairly soluble in acidic pH

  • in small intestine, Fe3+ may become ferric hydroxide (Fe(OH)3), which is relatively insoluble, making it less available for absorption

  • absorption of Fe3+ is increased by an acidic environment

  • Fe2+ is fairly soluble in alkaline pH

    • absorbed through divalent cation transporter (DMT 1)​

    • DMT1 transports any ions that carry 2 positive charges

    • low iron increases DMT1 synthesis

study question:

  • why are heme iron and nonheme iron digested and absorbed differentlt?

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Iron Absorption

Physiological Factors

  • current Fe status

  • low stores

  • increased need

    • pregnancy​

    • growth

    • hypoxia

    • blood loss

Dietary Factors

  • enhancers

    • sugars​

    • acids

    • MFP

    • mucin

  • inhibitors

    • polyphenols​

    • oxalic acid

    • phytates

    • phosvitin

    • Ca, Zn, Mn, Ni

    • vitamin A and C

Iron Transport & Uptake

  • ferrous Fe converted to ferric

  • ferric Fe in blood attached to transferrin

    • binding site at C terminal = high affinity to iron​

    • binding site at N terminal = low affinity to iron, will bind to other minerals

  • uptake by tissues

    • affected by transferrin saturation level​

    • transferrin binds to transferrin receptors to form a complex

    • complex internalized into vesicle

    • iron released from transferrin

    • apotransferrin returned to plasma

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Storage & Turnover

  • most iron goes to liver

    • taken up and binds to liver ferritin​

  • some iron goes directly to bone marrow for RBC synthesis

    • RBC is major site of body iron​

      • 60% of body iron​

  • spleen is another major storage site

  • ferritin is the primary storage form of iron in cells

    • synthesized​ in liver, bone marrow, spleen, intestine, and other tissues

    • ferritin is constantly synthesized and degraded, providing an intracellular iron pool

  • turnover: 

    • Hgb, ferritin, and hemosiderin degradation yield plasma iron​

  • excretion: 

    • most go through GI tract​

    • skin

    • urine

    • larger losses with blood loss

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Functions

  • iron functions as a part of several proteins

    • hemoglobin, myoglobin​

      • heme is the center of hemoglobin, myoglobin​

      • binds O2 in lungs, releases to tissues

    • cytochromes in ETC

      • ​heme is the center of cytochromes

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  • serves as a cofactor

  • pro-oxidant

    • fenton reaction​

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Deficiency

Risk Factors

  • rapid growth

    • 6mo - 4yo​

    • adolescents

  • increased needs

    • pregnancy​

  • disease

    • celiac​

    • chronic blood loss

  • vegetarians

    • especially vegans​

  • food insecurity

Stages of Iron Depletion

Key point: depletion doesn't lead to anemia at the beginning

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STAGE 1: early negative iron balance

  • plasma ferritin decreases

  • stores start to diminish

  • slight decrease in transferrin saturation

  • normal erythropoiesis, so no anemia

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STAGE 2: iron depletion

  • plasma ferritin continues to decrease

  • still not enough to compromise RBC

  • may compromise key enzymes

  • still have normal RBC indicators

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STAGE 3: iron-deficient erythropoiesis

  • large decrease in ferritin

  • increased transferrin binding capacity

  • % transferring saturation decreased

  • increased erythrocyte protoporphyrin

    • ​—Heme synthesis needs both Fe and protoporphyrin

    • decreased Fe leads to increased erythrocyte protoporphyrin

study question:

  • why does transferring binding capacity increase?

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STAGE 4: iron-deficiency anemia

  • low in RBC, Hgb, Hct

    • microcytic​

    • hypochromic

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Toxicity

  • accidental overload in young children could be fatal

  • related to indigestion of excessive amounts of iron pills or vitamin/mineral pills

  • hemochromatosis

©2023 by Syracuse University Dr.Margaret Voss

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