Lipid Transport Flashcards
How are lipids transported in the blood?
Inside lipoproteins such as:
Chylomicrons VLDL (Very low density) IDL (Intermediate density) LDL (Low density) HDL (High density)
What are the components of a lipoprotein and what is their function?
Phospholipid monolayer -
Forms capsule.
Peripheral apolioproteins and integral apolioproteins -
Act as co-factors for enzymes and ligands for receptors.
What are chylomicrons and how are they metabolised?
Chylomicrons are lipoproteins that transport dietary TAGs to adipose tissue.
Chylomicrons travel through lymph system and drain into the left subclavian vein to enter systemic circulation. Along the way several apolioproteins are added.
apoC binds to lipoprotein lipase on adipocytes and muscle which causes the chylomicron to release its content.
When chylomicron is only 20% full apoC dissociates and the chylomicron is transported to the liver where it’s broken down. The liver uses the rest of the TAG.
What is VLDL and how is it metabolised?
Produced in the liver to transport TAG to other tissue.
It binds the lipoprotein lipase on endothelial cells in muscle and adipose tissue.
This causes the VLDL to begin to release its TAG content.
When it has depleted a little it returns to the liver.
If it has depleted to 30% TAG it will become an IDL particle.
How is IDL metabolised?
When formed from the VLDL the IDL may also return to the liver to be metabolised.
Or it may rebind to lipoprotein lipase and continue to be depleted.
If it reaches 10% TAG content then it is now named a LDL
What is a LDL and how is it metabolised?
LDLs have a high cholesterol content and therefore their main function is to provide cholesterol from the liver to peripheral tissue.
Peripheral tissue contain LDL receptors. When LDL binds the cell engulfs LDL, containing the cholesterol inside.
What is the clinical relevance of LDL particles?
They have a much longer half-life than other lipoproteins.
This makes them susceptible to oxidative damage.
When damaged they will be engulfed by macrophages. However, these macrophages can then form foam cells.
Foam cells contribute to the formation of atherosclerotic plaque.
What is HDL and how is it metabolised?
HDL is a lipoprotein made to transport excess cholesterol from peripheral tissue to the liver.
Nascent (empty) HDL is produced in the liver.
It enters systemic circulation and absorbs cholesterol from endothelial cells.
HDL then transports the cholesterol either back to the liver, to tissue requiring it for the production of steroid hormones or to LDL.
What are hyperlipoproteinaemias?
Raised levels of one or more lipoproteins.
What is hypercholesterolaemia and its symptoms?
High levels of cholesterol in the blood.
Yellow patches on the eyelids.
Nodules on tendons.
White circle around the eye.
How can high levels of LDL cause problems?
Because of its long half-life it’s susceptible to oxidative damage.
Oxidised LDLs are engulfed by macrophages. If macrophages contain too much lipid they can become foam cells.
These foam cells accumulate in the intima of blood vessels which can develop into atherosclerotic plaque.
The plaque can stenose the vessel which can cause angina. If the vessel ruptures then the thrombus that forms can cause ischaemia leading to stroke or myocardial infarction.
How can hyperlipoproteinaemias be treated?
First -
Reduce cholesterol in diet.
More exercise.
Stop smoking to reduce risk of CVD.
Drugs -
Statins reduce cholesterol synthesis.
Bile salt sequestrants bind to bile salts in the GI tract. More bile salts must be made to replace them. Cholesterol is used to produce the bile salts.
