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Metabolism of iron

Metabolism of iron

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Metabolism of iron

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  1. Metabolism of iron Alice Skoumalová

  2. Iron in an organism: • total 3-4 g (2,5 g in hemoglobin) • heme, ferritin, transferrin • two oxidation states: Fe2+, Fe3+ • Function: • 1. Heme iron: • hemoglobin, myoglobin, cytochrom-c oxidase, catalase • 2. Non-heme iron: • Fe-S complexes (xanthine oxidase), DNA synthesis (ribonucleotide reductase) • Free iron is toxic ! • Regulation: • at the level of absorption

  3. Iron metabolism:

  4. Iron metabolism: • Recommended dietary allowance 10-15 mg • 10-50 mg in the diet (only 10-15% is normally absorbed) Iron distribution:

  5. Iron absorption from the intestine: D (DMT 1), I (Integrin), M (Mobilferrin), Fn (Ferritin), Fp (Ferroportin), H (Hephaestin), R (Ferrireductasa)

  6. Intestinal absorption of iron: • - in the duodenum • - regulation (by the synthesis of apoferritin within mucosal cells) • The heme iron (unknown mechanism) • The nonheme iron • is not readily absorbed (chelates with oxalates, phytates, etc.) • vit. C increases the uptake • Iron sources: • meat, liver, fish, eggs, green vegetables, cereals Iron loss: - daily loss ~ 1-2 mg (cell desquamation, ♀ menstruation, pregnancy, multiple births, lactation) - bleeding Recyclation of iron: - from aged erythrocytes (~ 20 mg) - transferrin receptors on cells

  7. Iron transport: • Transferrin (Fe3+) Transferrin + Fe3+ + CO32-→ Transferrin • 2(Fe3+CO32-) - only one third saturated with iron - unsaturated transferrin protects againsts infections (iron overload and infection) • Lactoferrin • - binds iron in milk • -antimicrobial effect (protects newborns from gastrointestinal infections) • Haptoglobin • - binds hemoglobin in the plasma • Iron storage: • Ferritin (Fe3+) - storage of iron (hepatocytes, RES, muscles) - in the blood → sensitive indicator of the amount of iron in the body • Hemosiderin - when iron is in excess (amorphous iron deposition)

  8. Iron-containing proteins: 1. Heme proteins Hemoglobin Myoglobin Enzymes that contain heme as their prosthetic group (catalase, peroxidase, NO synthase) 2. Nonheme proteins Transferrin Ferritin Enzymes that contain iron at the active site Iron-sulphur proteins

  9. Regulation of iron metabolism: • Hepcidin (a key regulator in iron metabolism) • ↓ resorption of iron in the intestine → ↓ concentration of iron in plasm • mechanism: binding to ferroportin (the iron is trapped in the cell) • increased concentration in inflammation (chronic disease anemia) • reduced production → hereditary hemochromatosis

  10. Iron deficiency (sideropenia): • Causes • inadequate intake, reduced resorption, increased loss • Symptoms • reduction of iron stores in liver and bone marrow • decrease in the amount of plasma ferritin • decrease in the percentage saturation of serum transferrin • decrease in the level of Hg, morphological changes of erythrocytes • microcytic hypochromic anemia (excessive menstrual flow, multiple births, GIT bleeding) • Therapy • supplementation

  11. Iron overload → hemochromatosis: • Causes • genetic - iron uptake regulation (hereditary hemochromatosis) • treatment of patients with hemolytic anemias • excessive ethanol and iron ingestion • Symptoms • accumulation of iron in the liver, pancreas and heart • Therapy • bloodletting, chelating agents

  12. Summary: 1. Function of iron (O2 transport, redox reactions , detoxification, cell division) 2. Iron can be toxic 3. Complicated regulation at the level of resorption 4. Iron is important for microorganisms 5. Abnormalities of iron metabolism → diseases

  13. Pictures used in the presentation: Marks´ Basic Medical Biochemistry, A Clinical Approach, third edition, 2009 (M. Lieberman, A.D. Marks) Textbook of Biochemistry With Clinical Correlations, sixth edition, 2006 (T.M. Devlin)