S2: Lipid Transport Flashcards
List places lipids are transported from
- Gut to the liver
- The liver to non hepatic tissue including adipocytes
- Non-hepatic tissue back to the liver
List the percentage of different types of fats and lipids in circulation
- Triacylglycerol (triglycerides) (45%)
- Cholesterol esters and free cholesterol (15%)
- Phospholipids (35%)
Free fatty acids (5%)
The % given in human plasma varies greatly with nutritional state
Do fats and lipids dissolve in plasma?
All are insoluble in water, they are not transported completely freely dissolved in the blood. This is because they are hydrophobic and also they interfere with membrane structure (being components of membranes themselves)
What are free fatty acids? How are they transported?
- Formed from triacylclycerides broken down into glycerol and free fatty acids
- Stored in adipose tissue
- They are transported bound to albumin as Na+ salt
- Fatty acids enter cells by simple diffusion and intracellular concentration of FFA is kept low
How are the majority of lipids transported in the blood?
They are transported in the blood as plasma lipoprotein. These are relatively large structures consisting of both lipid and large proteins (called apolipoproteins),
What are the 5 types of lipoproteins?
What are they classified by?
- Chylomicrons
- Very low density lipoproteins (VLDL)
- Intermediate density lipoproteins (IDL)
- Low density lipoproteins (LDL)
- High density lipoproteins (HDL)
They are classified by their density.
Chylomicrons have the lease density but are the largest in size. HDL have the highest density.
What is a lipoprotein?
Large protein with phospholipids orientated around the outside (similar to membrane) but in a single layer. The hydrophobic core contains compounds such as cholesterol esters and triglycerides.
Compare lipoprotein composition of chylomicrons and HDL
Chylomicrons have a very low density, they have high TG and low protein.
HDLs have a very high density with low TG and high protein.
List multiple functions of apolipoproteins/apoproteins
- Structural = form a substrate in which lipid can be constructed
- To solubilise lipids= allowing body to transport a difficult class of molecules
- Act as enzymes or enzyme cofactors= Apo C2 helps activate lipoprotein lipase, Apo A1 transfers some lipids between particles
- Allow tissue targeting to specific tissues= Apo B100 and Apo E bind to the LDL receptor, Apo E also binds to the HDL receptor
Explain the course of dietary lipids
Triglycerides we consume are broken down by lipases in the gut to fatty acids and monoacylglycerols
The triglycerides are then assembled into a chylomicron along with other lipids (phospholipids and cholesterol) and proteins. They are low density
due to high TG.
Chylomicrons are then released into the lymphatics which carries them via the thoracic duct to the SVC - secreted by reverse pinocnocytosis. By this pathway dietary fats avoid the direct delivery to the liver and instead made available to extrahepatic tissue (i.e. they have first call). This is very different to digested proteins and carbs which are released into the portal vein and delivered directly to the liver.
Apo C2, C3, E and B48 added in the SER
Explain removal of fatty acid from lipoprotein
Lipoprotein lipase (LPL) is expressed on top of endothelial cells and this is activated by the apolipoprotein Apo C2
When LPL is activated, the TG is broken down and there is diffusion of across the membrane of free fatty acid.
This continues as the chylomicron goes around the circulation and it gains density
Compare the KM of LPL isoform in adipocyte and muscle
Km adipocyte > muscle
What stimulates LPL on endothelial cells and adipocyte?
LPL activated by Apo C2 on endothelial cells
LPL on adipocyte activated by insulin
Name 3 types of hyperlipidaemia (high levels of circulating lipids)
Type 1: Deficiency by lipoprotein lipase or Apo C2 - characterised by high plasma triglycerides
Type 2: Most caused by genetic defect in synthesis processing or function of LDL receptor - characterised by high LDL
Type 4: Often due to obesity or alcohol abuse - most common form results in raised VLDL concentrations
Describe chylomicrons
- Contents reflect meal composition
- Low density due to TAG (triaglycerol)
- Contain fat soluble vitamin A and vitamin E (important for preventing oxidation of lipids)
- Circulate for 1 hr but half life of TAG is only 5 mins so they are rapidly modified by LPL which breaks down TAG causing uptake of fatty acid by tissue
- As chylomicrons go round the circulation, the density of these particles increase as chylomicron remnants (TAG) is removed by the liver. This is done by interaction of Apo E with receptors on hepatocytes
How are chylomicron remnants removed?
How does this affect density?
They are removed by the liver. This is done through interaction of Apo E with receptors on hepatocytes.
This increases density as TAG is removed