Cholesterol 4 Flashcards
What are the features of cholesterol reverse transport?
As cholesterol cannot be degraded it is returned from peripheral tissues to either the liver or steroid producing tissues
Efflux is rapid with roughly 0.1% of total cell cholesterol being cleared per minute
Apo-A1 containing HDLs picks up cholesterol from tissues
What is the relationship between HDL concentration and heart disease?
Inverse relationship, believed to be due to reverse cholesterol transport
What is tangiers disease?
It is a genetic disorder where there are orang, lipid-engorged tonsils
HDL deficiency
Accumulation of cholesterol in macrophages
Premature atherosclerosis
What causes Tangiers disease?
A mutation in an ATP-Binding-Cassette (ABC) transporter which usually has the function of exporting cholesterol and phospholipids for uptake into HDL
What is the normal cholesterol efflux pathway?
Free cholesterol is obtained either through synthesis, recycling from lipoproteins or cholesterol ester droplets
This is then exported via the ABC transporter protein where it combines with the extracellular pre-beta-HDL formed from Apo-A1 particles in the liver leading to the formation of a preHDL
Lecithin-cholesterol acyl transferase is then used to enrich the preHDL into an HDL by producing cholesterol esters
These HDLs will then either be taken up by the liver or steroid producing tissues as a source of cholesterol or they can transfer their cholesterol esters to other lipoproteins through cholesterol-ester transfer protein
How does HDL transfer its cholesterol to the liver and steroid producing tissues?
HDL binds to a scavenger receptor, SR-B1
The lipids and cholesterol are then transferred to the tissue and the HDL will then go and pick up other cholesterol and phospholipid cargo
How are HDLs protective of atherosclerosis?
HDLs can promote removal of cholesterol from cells including the macrophage/foam cells through reverse cholesterol transport
Thus the risk of atherosclerosis can be seen as a balance between LDL delivery and HDL removal
Paroxinase is a serum esterase associated with HDLs and capable of destroying the oxidated LDLs
HDL has anti-inflammatory processes
What is responsible for the accumulation of cholesterol by foam cells?
LDL near the arterial wall may be damaged through oxidative reactions promoted by inflammatory cells
This leads to the oxidation of unsaturated fatty acids generating aldehydes which modify proteins and other LDL components
The modified LDLs can bind to scavenger receptor which is normally there to promote endocytic destruction of damaged molecules/cells, these are not normally part of cellular cholesterol metabolism and so not regulated
