Metabolism of iron Alice Skoumalová. Iron in an organism: total 3-4 g (2,5 g in hemoglobin) heme,...

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)