Iron Absorption and Transport

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Iron Absorption and Transport - Rusty Essentials

  • Absorption: Duodenum (Fe²⁺ form). Non-heme Fe³⁺ reduced by DcytB.
  • Enterocyte Uptake: Heme (HCP1); Fe²⁺ (DMT1).
  • Basolateral Export: Ferroportin (Fe²⁺). 📌 Ferroportin = For Passage Out.
  • Oxidation: Hephaestin (enterocyte) / Ceruloplasmin (plasma) convert Fe²⁺ → Fe³⁺.
  • Blood Transport: Transferrin carries Fe³⁺.

    ⭐ Hepcidin, a liver hormone, is the main negative regulator, blocking iron export by degrading ferroportin. Iron absorption and transport pathway

Iron Absorption and Transport - The Gut Gate

  • Dietary Iron:
    • Heme (meat): Absorbed by HCP1 (Heme Carrier Protein 1).
    • Non-heme ($Fe^{3+}$, plants): Needs reduction to $Fe^{2+}$ (ferrous).
  • Duodenal Enterocyte Uptake (Apical):
    • Non-heme $Fe^{3+}$ $\xrightarrow{DcytB \ (reductase)}$ $Fe^{2+}$.
    • $Fe^{2+}$ enters via DMT1 (Divalent Metal Transporter 1).
    • Heme enters via HCP1; Heme Oxygenase releases $Fe^{2+}$ intracellularly.
  • Intracellular $Fe^{2+}$ & Basolateral Export:
    • Storage: As ferritin (stores $Fe^{3+}$).
    • Export: $Fe^{2+}$ via ferroportin (FPN1).
      • $Fe^{2+}$ $\xrightarrow{Hephaestin \ (Cu-ferroxidase)}$ $Fe^{3+}$.
      • $Fe^{3+}$ binds plasma transferrin.

⭐ DMT1 is the key apical transporter for non-heme ferrous iron; ferric iron is not its substrate.

Iron absorption and transport in enterocyte

Iron Absorption and Transport - Bloodstream Bound

  • Basolateral Export from Enterocyte:
    • $Fe^{2+}$ exits via Ferroportin (FPN1).
    • Hephaestin: Membrane-bound ferroxidase (Cu$^{2+}$-dependent); oxidizes $Fe^{2+}$ to $Fe^{3+}$ at basolateral membrane for plasma loading.
    • Ceruloplasmin: Plasma ferroxidase (Cu$^{2+}$-dependent); also oxidizes $Fe^{2+}$ to $Fe^{3+}$.
  • Plasma Transport (Bound to Transferrin):
    • Transferrin (Tf): Main iron transport protein; binds 2 $Fe^{3+}$ ions per molecule.
      • Synthesized in liver.
      • Delivers iron to cells with Transferrin Receptors (TfR1), especially erythroid precursors.
    • TIBC (Total Iron Binding Capacity): Indirect measure of circulating transferrin. ↑ in iron deficiency, ↓ in iron overload/inflammation.

⭐ Normal transferrin saturation (Serum Iron / TIBC × 100) is 20-50% (average ~33%). Values <16% suggest iron deficiency.

  • Regulation:
    • Hepcidin: Key regulator; binds ferroportin, causing its internalization & degradation, thus ↓ iron release into blood from enterocytes and macrophages.

Iron Absorption and Transport - Hepcidin's Command

  • Hepcidin: Key peptide hormone from liver; master regulator of systemic iron.
  • Mechanism: Binds ferroportin (FPN1) → internalization & degradation of FPN1 → ↓ iron export from enterocytes/macrophages into blood.
  • Regulation of Hepcidin Synthesis:
    • Upregulation (↑ Hepcidin):
      • High iron stores (sensing via HFE, TfR2, HJV)
      • Inflammation (IL-6 via STAT3 pathway)
    • Downregulation (↓ Hepcidin):
      • Iron deficiency
      • Hypoxia (HIF-dependent pathways)
      • Increased erythropoietic activity (Erythroferrone - ERFE)

Hepcidin regulation of ferroportin and plasma iron

⭐ Hepcidin dysregulation is central to iron disorders: low hepcidin in hemochromatosis, high hepcidin in anemia of chronic disease (ACD).

High‑Yield Points - ⚡ Biggest Takeaways

  • Iron absorption predominantly occurs in the duodenum and proximal jejunum.
  • Dietary iron: Heme iron (Fe2+) is better absorbed than non-heme iron (Fe3+).
  • Apical uptake: DMT1 transports Fe2+; DcytB reduces Fe3+ to Fe2+.
  • Basolateral export: Ferroportin transports iron out, aided by hephaestin (oxidation).
  • Plasma transport: Transferrin binds and transports Fe3+ in blood.
  • Key regulator: Hepcidin inhibits iron absorption by degrading ferroportin.
  • Storage: Iron is stored intracellularly as ferritin (Fe3+ form).

Practice Questions: Iron Absorption and Transport

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All of the following decrease in iron deficiency anemia except:

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Flashcards: Iron Absorption and Transport

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_____ is a measure of transferrin molecules in the blood

TAP TO REVEAL ANSWER

_____ is a measure of transferrin molecules in the blood

Total iron-binding capacity (TIBC)

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