L11 - Absorption of iron and gastrointestinal disease WIP Flashcards
What is the role of iron in human biology?
- O2 transport and storage (Hb and Mb)
- Electron transport (cytochromes contain iron, no iron means can’t make ATP)
- Plethora of enzymes
- Cell cycle control (regulation of progression between stages of cell cycle)
What are the two main types of iron found in diet?
- Haem iron
- Red meat
- Poultry
- Seafood - Non-haem iron (inorganic)
- Nuts
- Beans
- Vegetables
- Whole grains
Describe the process of luminal enterocyte iron uptake
- Fe3+ in lumen is reduced to Fe2+ (ferric reductase) by duodenal cytochrome B (DcytB)
- DMT1 (divalent metal transporter - a brush border protein on the apical membrane of the enterocyte) is responsible for ferrous uptake into the enterocyte cell
- Once in the cell, Fe2+ can either bind with ferritin for inert iron storage within the cell or it is transported out of the cell via ferroportin into the blood stream (cellular iron efflux)
- In the blood, Fe2+ is oxidised to Fe3+ by hephaestin (ferroxidase)
- The Fe3+ is then bound with apo-tf (transferrin) to circulate in the blood stream (it is essential for iron binding in the blood) - makes holo-tf?
How do iron stores communicate with the small bowel?
With hepcidin (protein regulator of iron metabolism)
hep => produced in the liver
Cidin => bacteriocidal properties
How do iron stores communicate with the small bowel?
With hepcidin (protein regulator of iron metabolism)
hep => produced in the liver
Cidin => bacteriocidal properties
Describe the regulation of iron in the body
- Tight regulation is crucial
- Because body iron levels are relatively constant
- Can’t really excrete iron as there is no active secretory mechanism, only lose a small amount
What triggers start/ stop of absorption of iron?
- Low iron levels TRIGGER absorption
2. High iron levels STOPS absorption
What is the physiological processing of iron?
- Done via “iron cycle”
- V small amounts of iron absorbed via diet in small bowel
- Stored in liver
- V small amounts of iron lost everyday in sweat, loss of mucosa
Describe haem transport of iron
- Via haem carrier protein (HCP1) at brush border of enterocyte (important for haem import)
1. Once into cell, haem broken down by haem-oxygenase 1 (HO-1)
2. Releases free iron and biliverdin
3. Enters labile iron pool within cell
4. Exported by ferroportin or stored by ferritin
Function of HO-1 (haem-oxygenase 1)?
Haem catabolism to release free iron and biliverdin
What is intravascular haemolysis?
When RBC ruptures as a result of the complex of complement autoantibodies attached on the surfaces of RBC’s attack and rupture RBC’s membranes, or a parasite exits the cell that ruptures the RBC’s membrane as it goes
- Releases haemoglobin into plasma (free Hb)
- Mechanical trauma
- Complement fixation
- Toxic dmg to RBC
What happens to free Hb in the plasma?
(Free Hb in plasma released from intravascular haemolysis)
- Bound to haptaglobin
- Expresses receptors for haptaglobin
- Quantity of free plasma haptaglobin decreases in direct proportion to amount of Hb being released through eythrocyte lysis
- Directed to macrophages
- Broken down into haem and globin
- Haem broken decomposed into biliverdin and free iron (biliverdin is eventually converted to bilirubin)
What could be a consequence of an excess of breakdown from biliverdin into bilirubin?
Hyperbilirubinaemia
What is haem biosynthesis?
- A biochemical pathway with multiple complex steps and lots of enzymes
- Defects can lead to disease
What is the consequence of a deficiency in an enzyme or substrate of the haem biosynthesis pathway?
Accumulation of intermediates of haem synthesis in blood, tissues and urine leading to clinically significant outcome of a group of disorders called porphyrias
