1. Microminerals (trace elements) Iron
Dr. Sherin Bakhashab

2. Iron Sources: Recommended daily allowance:
Liver, heart, meat, spleen and fish
Egg yolk and dates
Recommended daily allowance:
The RDA for adult man is 10 mg/ day, and for woman is 18 mg/day.

3. Absorption Mechanism of absorption:
Absorption of iron occurs mainly in the duodenum.
Diet contains about mg iron/day, but only % of this amount is absorbed.
Mechanism of absorption:
a) The pathways responsible for the absorption differ partially for non-heme and heme iron.
b) Luminal non-heme iron is mostly in ferric state (Fe+++) and must first be reduced to ferrous state (Fe++) by ferrireductases.
c) Fe++ is then transported across the apical membrane by divalent metal transporter 1 (DMT1).

4. Absorption
c) Heme iron is moved across the apical membrane into the cytoplasm through transporters.
d) Inside mucosal cells, iron either:
Transported through the cell to the circulation.
Incorporated into ferritin, i.e. ferritin acts as storage compound.
e) Fe++ iron moved to circulation, is transported through the cell membrane by ferripotin.

5. Absorption of iron from duodenum

6. Absorption
f) This process is coupled to oxidation of Fe++ iron to Fe+++ iron, which is carried out by the iron oxidases hephaestin. g) Fe+++ iron binds to the plasma protein transferrin, which delivers iron.

7. Factors affecting iron absorption
Most of the dietary iron is present in the ferric state (Fe+++) as ferric organic compounds.
Factors promoting iron absorption:
Cooking of food and gastric HCl facilitate the liberation of Fe+++ from organic compounds.
Reducing substances: vitamin C and cysteine (-SH) of dietary protein help the reduction of Fe+++ into the absorbable ferrous state (Fe++).
Body needs: absorption occurs only if the body need iron. More iron is absorbed when there is iron deficiency or when erythropoiesis is increased.

8. Factors affecting iron absorption
B. Factors inhibiting iron absorption:
Hepcidin:
Hepcidin is synthesized by liver in response to increase in intrahepatic iron levels.
Hepcidin inhibits iron transfer form the intestinal cells to plasma by binding to ferriportin.
With low body stores of iron, hepcidin synthesis falls and this in turn facilitates iron absorption.
High dietary phosphate and phytate: They form insoluble, non-absorbable organic iron complexes.
Steatorrhea: where fatty acids form non-absorbable iron soaps.
Alkalies and tea.
Phytate storage form of phosphorus

9. Body iron It is distributed as follows: The total body iron is 4-5 g.
Hemoglobin (RBCs iron): 66% it is the largest pool of body iron.
Tissue iron: 33%
Plasma iron: 1%

10. Tissue iron
Tissue iron include:
A. Available forms (29%): can be used by tissues when there is body need.
Ferritin:
It is the main storage form of iron.
It is formed of a protein called apoferritin which can carry 24 atoms of iron to form ferritin.
It is present in iron stores: liver, spleen, bone marrow and intestine.

11. Tissue iron 2) Hemosiderin:
When body contains very high content of iron more than the capacity of apoferritin, some of iron is found in granules called hemosiderin.
These granules composed of iron, protein and polysaccharides.

12. Tissue iron
B. Non available forms (4%): can not be used even if there is body needs. All these forms are hemeprotiens, i.e. contain heme ring.
Myoglobin:
It is hemeprotein formed of a single heme ring
It is present in muscles and heart.
It acts as oxygen reserve for quick utilization by contracting muscles.

13. Heme

14. Non available forms 2) Respiratory cytochromes (b,c1, c, a, a3):
These are components of respiratory chain in mitochondria.
They act as electron carriers.
3) Catalase and peroxidase:
These 2 enzymes act on the toxic hydrogen peroxide (H2O2) converting it to H2O.

15. Non available forms

16. Non available forms 4) Tryptophan oxygenase:
This enzyme is important for tryptophan metabolism.
5) Cytochrome P450 :
These are specific group of enzymes that are present in most tissues of the body.
These enzymes are primarily membrane-associated proteins located either in the inner membrane of mitochondria or in the endoplasmic reticulum of cells.
They act as electron carriers.
The Human Genome Project has identified 57 human genes coding for the various cytochrome P450 enzymes.
Cytochrome P450 enzymes metabolize toxic compounds, including drugs and products of endogenous metabolism such as bilirubin, principally in the liver.

17. Plasma Iron Plasma iorn: ranges from 60-160 µg/ dl. Transferrin:
This is an iron containing glycoprotein synthesized in the liver.
Each molecule can carry 2 atoms of iron in ferric state (Fe+3 ).
Transferrin may carry up to µg iron /dl. This is known as total iron binding capacity (TIBC).
TIBC is a measure of the amount of iron that can bound with plasma transferrin.
In iron deficiency anemia, plasma iron is decreases. Liver synthesizes more transferrin with subsequent increase of TIBC.
In liver disease: both plasma iron and transferrin synthesis tend to decreased decrease TIBC.

18. Plasma Iron c) Plasma ferritin:
Very low plasma ferritin is present in plasma.
Measurement of plasma ferritin gives a good indication about body iron stores.
A low plasma ferritin indicates the presence of depleted iron stores, e.g. in iron deficiency anemia.
A raised plasma ferritin is found in iron overload and in many patients with liver disease and cancer.

19. Functions of Iron
Iron enters in the structure of the following compounds:
Hemoglobin: which carries oxygen.
Myoglobin: which stores oxygen.
Respiratory enzymes: which uses oxygen.
Cytochrome P450 : which detoxifies drugs and oxygen.

20. Transport and storage of Plasma iron
Absorbed iron enters in the portal blood in ferrous state (Fe++).
In the plasma it is rapidly oxidized to ferric state (Fe+++). This oxidation is catalysed by a protein containing copper called ceruloplasmin.
Ferric ions are carried by transferrin, which is taken mostly by bone marrow to synthesize haemoglobin.
Iron from iron stores (ferritin) can be released into plasma and carried by transferrin to be utilized by bone marrow and other tissues.

21. Excretion
Iron excreted in the feces is mainly exogenous, i.e. dietary iron that has not been absorbed.
In females there are additional sources of loss, due to menstruation and pregnancy.
Urine contains negligible amount of iron.

22. Metabolic disturbances
Iron deficiency may result from:
Inadequate intake
Impaired absorption, in gastrointestinal disturbances
Excessive loss, example: menstrual loss, gastrointestinal bleeding.
B. Iron excess (siderosis): this term is used to describe the presence of excess iron in the body. In this case, excess iron is accumulated in the liver as hemosiderin.
This may occur under several cases:
Hemolytic conditions: excess iron accumulates in the tissues of patients with all types of hemolytic anemia, where red blood cells are broken.
Repeated blood transfusion may lead to siderosis, since the iron liberated form the broken cells is not excreted.
In some diseases: sever hepatitis, due to release of iron from the liver.