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Metabolism of iron
Alice Skoumalová
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
Iron metabolism:
Iron metabolism:
Recommended dietary allowance 10-15 mg
10-50 mg in the diet (only 10-15% is normally absorbed)
g %
Hemoglobin 2,5 68
Myoglobin 0,15 4
Transferrin 0,003 0,1
Ferritin, tissue 1,0 27
Ferritin, serum 0,0001 0,004
Enzymes 0,02 0,6
Total 3,7 100
Iron distribution:
Iron absorption from the intestine:
D (DMT 1), I (Integrin), M (Mobilferrin), Fn (Ferritin), Fp (Ferroportin), H (Hephaestin), R (Ferrireductasa)
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
Iron transport:
Transferrin (Fe3+) Transferrin + Fe3+ + CO32- → Transferrin • 2(Fe3+CO3
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 (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)
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
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
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
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
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
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)