L.6 Iron Metabolism & Disorders Flashcards
Iron absorption steps
- Ingestion of dietary iron
Non-heme = ferric form Fe3+
Heme = ferrous form Fe2+ - Ferric complexes of non-heme sources are not easily absorbed - gastric acid solubilizes this iron.
- Iron released from protein complexes by proteolytic enzymes in stomach.
- Ferric iron (Fe3+) reduced to ferrous state (Fe2+) at brush border of enterocytes by Dcytb
- Ferrous transported across entercyte plasma membrane into cytoplasm by DMT-1 (membrane protein)
Acidic pH of stomach facilitates transport. - In enterocyte, iron stored as ferritin
Iron storage
Stored as ferritin
Lost when enterocyte is sloughed off into intestinal tract.
Iron release from enterocytes
- Iron moves from enterocyte to circulation through membrane protein Ferroportin-1.
- Hephaestin oxidizes iron Fe2+ to Fe3+ form which is required for binding to apotransferrin.
What protein regulates movement of iron into plasma by ferroportin?
Hepcidin
What is the site in the Hb molecule where oxygen reversibly binds?
Iron held at the centre of the porphyrin ring
Iron is crucial for oxygen transport in hemoglobin.
What are the two forms of iron supplied in the diet?
- Haem iron
- Non-Haem iron
Where is Haem iron derived from?
Hb, myoglobin from food of animal origin
What is the form of Non-Haem iron?
Ferric Fe+++ form
How is Non-Haem iron converted before absorption?
Converted to the ferrous form
What is the recommended daily intake of iron for a healthy diet?
Approx 15mg iron/day
What amount of iron do we need to absorb daily?
1-2 mg/day
List some sources of dietary iron.
- Red meat
- Liver
- Green vegetables
- Poultry
- Dried fruit
What increases iron absorption in the body?
Foods containing ascorbic acid and muscle protein
What can inhibit iron absorption?
Caffeine
How much iron does the typical adult human body contain?
About 3-5 grams of iron
What are the vital roles of iron in the body?
- Synthesis of haem, myoglobin, cytochromes
- Co-factor in DNA synthesis
- Connective tissue production
What happens to excessive iron in the body?
It is toxic to the body.
Where is iron primarily found in the body?
- Red blood cells (RCs)
- Macrophages
- Hepatocytes
- Enterocytes
How much iron is lost from the body per day?
1-2 mg of iron
What factors increase the efficiency of intestinal absorption of iron?
Accelerated erythropoietic activity and depletion of body iron stores
What can result in accelerated erythrocyte production?
- Bleeding
- Hypoxia
- Haemolysis
Is there a physiological mechanism for the excretion of iron?
No
Where does control of iron balance occur?
At the level of iron absorption (duodenum and jejunum)
What factors modify iron balance?
- Dietary excess (over supplementation)
- Inherited protein defect (haemochromatosis)
- Anaemia (ineffective erythropoiesis)
- Iatrogenic (Red Cell Transfusions)
What is Hepcidin?
Master iron regulating protein
What role does Hepcidin play in iron balance?
Regulates iron recycling/balance via interaction with ferroportin 1
What is the function of DMT1?
Transports iron across the enterocyte apical plasma membrane
What does Ferroportin 1 do?
Transports iron across the basolateral membrane of the enterocyte
What is the role of Hephaestin?
Facilitates cellular export of iron & oxidizes Fe2+ to Fe3+ for binding to apotransferrin
What is the first step in iron absorption?
Dietary iron exists in 2 forms: Non-heme (Fe3+) & Heme (Fe2+)
What does gastric acid do to iron?
Solubilizes this form of iron and provides an acidic environment
What enzyme reduces ferric iron Fe3+ to ferrous iron Fe2+?
DcytB (duodenal cytochrome b)
What happens to iron in the enterocyte?
- Stored as ferritin
- Transported across the basolateral membrane into the plasma
How is iron transported across the basolateral membrane?
By Ferroportin 1
What happens to iron when it enters circulation?
Oxidized by Hephaestin to Fe3+ for binding to transferrin
What is Transferrin?
Transports iron around the blood
What is the significance of transferrin saturation?
Indicates body iron status
What is the formula to calculate % transferrin saturation?
Serum iron/TIBC x 100%
How does iron enter developing RBCs?
By receptor-mediated endocytosis through TfR on the RC membrane
What happens to excess iron taken up by developing erythroblasts?
Stored as Ferritin
Where is iron stored in the body?
- Bone marrow
- Liver
- Pancreas
- Spleen
What is Haemosiderin?
Formed from aggregates of ferritin, found primarily in macrophages
What is Ferritin?
Primary iron storage protein found in the bone marrow, liver, spleen
What is the role of Hepcidin in iron absorption?
Inhibits absorption when iron stores are adequate
What factors lead to high hepcidin levels?
- Chronic kidney disease
- Dialysis
- Genetic factors
- Infectious/inflammatory disease
What condition is characterized by increased absorption of iron from the GI tract?
Hereditary Haemochromatosis (HH)
What mutation is associated with Hereditary Haemochromatosis?
C282Y mutation
What is the treatment for Hereditary Haemochromatosis?
Phlebotomy
