5 Lipid transport Flashcards
How do we get cholesterol?
Some dietary
Mainly synthesised in the liver
Lipids are hydrophobic, what does this mean?
- insoluble in water
- problem for transporting in blood
- transported in blood by carriers:
-albumin - fatty acids
-lipoprotein particles
Lipoprotein definition
Sphere of phospholipids used to transport lipid in bloodstream
Chylomicron function
Transports dietary TAGs from intestines to tissues
VLDL function
Transports liver synthesised TAGs to adipose tissue for storage
IDL function
Transports liver synthesised cholesterol from liver to tissues
LDL function
Transport of liver synthesised cholesterol to tissues
HDL function
Transports excess cholesterol from peripheral tissues to liver for disposal as bile salts
Density of lipoproteins order
Least
Chylomicron
VLDL
IDL
LDL
HDL
Most
Size of lipoprotein order
Biggest
Chylomicron
VLDL
IDL
LDL
HDL
Smallest
When are Chylomicrons present in blood?
4-6 hours after eating
What do chylomicrons look like after flotation ultracentrifugation?
Creamy appearance
How is density of lipoproteins measured?
Flotation ultracentrifugation
Apolipoprotein definition
Peripheral and integral proteins on lipoproteins
Peripheral - on top
Integral - pass through
Apolipoprotein function
- structural: packaging water insoluble lipids
- functional: cofactor, ligands for cell surface receptor
Lipoprotein lipase function
Hydrolyses TAGs in lipoprotein
Needs ApoC-II as cofactor
What is the cofactor of lipoprotein lipase?
ApoC-II
When does a Chylomicron become a Chylomicron remnant?
When lipid content drops below 20%
Relationship between VLDL,IDL and LDL
VLDL > IDL > LDL
IDL - 30% depletion
LDL - 10% depletion
What is bad cholesterol?
Why?
LDL
- Longer half life: more susceptible to oxidative damage
- no apoC/E: no efficiently cleared by liver
What happens to oxidised LDLs?
Taken up by macrophages
Foam cells form
Can cause atherosclerosis
How do LDLs enter tissues?
Receptor mediated endocytosis
What happens in receptor mediated endocytosis?
Receptors for ApoB-100 ligand on LDL allow LDL to be endocytosed
LDL digested by lysosomes
What is good cholesterol?
Why?
HDL
- Removes excess cholesterol from peripheral tissues
- Takes to liver or steroidogenic cells to be removed
- Reduced chance of foam cells and forming atherosclerotic plaques
Hyperlipoproteinaemia defintion
High levels of 1 or more classes or lipoprotein
Causes of hyperlipoproteinanemia
Overproduction
Under removal
What is type I hyperlipoproteinaemia?
Chylomicron present in plasma even when fasting
Due to defective LPL
What is type IIa hyperlipoproteinaemia?
- High levels of oLDL > foam cells > risk of atherosclerosis
- Due to defective LDL receptor so LDL gets oxidised
familial hypercholesteroaemia
What is type III hyperlipoproteinaemia?
Raised IDL and Chylomicron remnants
Due to defective apoE
What is the first treatment of hyperlipoproteinaemia?
- DIET : reduced saturated fats and lipids, increase fibre
- LIFESTYLE : exercise, stop smoking - reduces cardiovascular risk
Second treatment of hyperlipoproteinaemia
- STATINS : inhibits HMG-CoA reductase, used in cholesterol synthesis so less cholesterol made
- BILE SALT SEQUESTRANTS - bind bile salts in GI tract so liver produces more bile acids (uses cholesterol)
What is hypercholesteroaemia?
High levels of cholesterol in blood
What is the normal cholesterol level in blood?
<5mmol/L
Signs of hypercholesteroaemia
- XANTHELASMA : yellow patches on eyelids
- TENDON XANTHEMA : nodules on tendons
- CORNEAL ARCUS : white/blue circle around eye
What is xanthelasma and what it is a sign of?
Yellow patches on eyelids
Hypercholesteroaemia - high levels of cholesterol
What is tendon xanthema and what is it a sign of?
Nodules on tendon
Hypercholesteroaemia- high levels of cholesterol
What is corneal arcus and what is it a sign of?
Difference in young and older people
White/blue circle around eye
Hypercholesteroaemia- high levels of cholesterol
Normal in older people
Concerning in younger people
Process of plaque formation
1) LDL have longer half life so get oxidised
2) oLDL engulfed by macrophages
3) foam cells made + accumulate in intima of blood vessels
4) fatty streak formed
5) evolves into atherosclerotic plaque > angina
6) plaque ruptures
7) thrombosis (clotting) > stoke or myocardial infarction
What can a ruptured plaque cause?
Stroke
Myocardial infarction