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: Fe 2+, Fe 3+ 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.  Recommended dietary allowance 10-15 mg  10-50 mg in the diet (only 10-15% is normally absorbed) g% Hemoglobin2,568 Myoglobin0,154 Transferrin0,0030,1 Ferritin, tissue1,027 Ferritin, serum0,00010,004 Enzymes0,020,6 Total3,7100 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) 1.The heme iron (unknown mechanism) 2.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 (Fe 3+ ) Transferrin + Fe 3+ + CO 3 2- →Transferrin 2(Fe 3+ CO 3 2- ) - 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 (Fe 3+ ) - 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 (O 2 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)