L14 Cholesterol and Lipoprotein Metabolism Flashcards
What is the composition of a triglyceride?
Glycerol backbone and three fatty acids
What is the composition of a phospholipid?
Two fatty acids attached to glycerol and phosphate with a variable head group
What are some roles of cholesterol? (good and not so good) (3)
- Structural component of cell membrane for cell integrity and fluidity
- Precursor of steroid hormones, vitamin D and bile acids
- Accumulation in arteries leading to CHD and stroke
Where is cholesterol mainly synthesised?
Liver and intestine, however can be synthesised in all cells
What is cholesterol synthesis controlled by? (3)
- Dietary intake
- Cholesterol levels
- Hormones
What condition do ‘statins’ treat?
Hypercholesterolaemia
How are cholesterol levels normally balanced?
Balance between intake, synthesis, use, reabsorption and excretion
What is HMG-CoA reductase?
A rate limiting enzyme to control cholesterol synthesis
What is the structure of a lipoprotein?
Polar surface with phospholipids, cholesterol and proteins
Non-polar lipid core with TGs and cholesteryl esters
What is the main component of chylomicrons? Is it the highest or lowest density?
Triglycerides
Lowest density due to its high fat and low protein content
What is the main component of VLDL?
Triglycerides
What is the main component of LDL?
Cholesterol
What is the main component of HDL?
Protein
Where are chylomicrons produced?
Inside enterocytes
Where are VLDLs produced?
In the liver from chylomicron remnants and lipids
How are LDLs produced?
From VLDL (via IDL) after lipoprotein lipase removes triglycerides
Where are HDLs produced?
Initiated in the liver but mature in circulation
What apo-lipoporotein is associated with HDL?
apoA-I
What apo-lipoporotein is associated with LDL and VLDL?
apo-B100
What apo-lipoporotein is associated with chylomicrons and chylomicron remnants?
apoE
What is the main function of lipoproteins? (1)
What are its three pathways? (3)
- Used for transporting lipids
- Exogenous pathway - digestive system to liver
- Endogenous pathway - liver to other tissues
- Reverse transport - from tissues back to the liver
What are functions of apolipoproteins? (2)
- Helping stabilise lipoproteins
- Interact with receptors on cell surfaces
How does the exogenous lipid transport pathway work? (4 steps)
- Dietary lipids are packaged into chylomicrons inside enterocytes
- Chylomicrons are absorbed into the lymphatic system via lacteals
- Then enter the bloodstream via thoracic and right lymphatic ducts
- Remodelling of chylomicrons
How do chylomicrons work? (4 steps)
- Chylomicrons interact with capillaries of muscle and adipose tissue
- Lipoprotein lipase hydrolyses TGs
- FAs and glycerol enter the cell for storage or fuel
- Converted into chylomicron remnants that travel back to the liver
How does the VLDL lipid transport pathway work? (3 steps)
- Liver produces VLDLs which carry TGs and cholesteryl esters to tissues
- Lipoprotein lipase removes TGs from VLDL to cells
- Removal of TGs result in VLDL remnants which are mostly returned to the liver
How is LDL formed? (3 steps)
- Remaining VLDL remnants in circulation become IDLs
- Some IDLs are reabsorbed by the liver via LDL receptor
- Remaining IDLs are hydrolysed by hepatic lipase which forms LDLs
What lipoprotein is the main lipoprotein that transports cholesterol to cells in the body?
LDL
How is LDL taken up by cells? (3 steps)
- LDL’s apoB-100 binds to LDL receptor (LDLR) on the cell surface
- LDLR-mediated endocytosis occurs; cell membrane encloses LDL into a vesicle which enters the cell
- LDL is hydrolysed and cholesterol is released
What is the chain of events from an oversupply of cholesterol? (6)
- Increased intracellular cholesterol
- Inhibited cholesterol synthesis
- Inhibited LDLR synthesis
- Down-regulation of LDLR synthesis
- Decreased LDL uptake
- Hypercholesterolaemia
What happens when there is excess LDL? (2)
- LDL accumulates in the arterial walls
- May become oxidised leading to atheroma formation
How do HDL particles fill with cholesterol? (1)
By ApoAI binding to ABCAI
Describe HDL maturation (3 steps)
- HDL binding to ABCAI causes efflux of free cholesterol and phospholipids
- Free cholesterol is esterified by lecithin-cholesterol acyltransferase (LCAT) and stored as cholesterol esters
- Cholesterol esters move to hydrophobic core of particle and produces a mature HDL
Describe HDL reverse transport - direct pathway (2)
- HDL particles circulate and remove cholesterol from cells, and pick up phospholipids via phospholipid transport protein (PLTP)
- HDL then delivers cholesterol to the liver or steroidogenic organs such as adrenals, testes and ovaries
a) What does HDL use in its indirect transport pathway? (1)
b) What does it promote the transfer of? (2)
c) Why is this pathway beneficial? (1)
a) Cholesteryl ester transfer protein (CETP)
b) Promotes the transfer of:
- TG from VLDL and LDL to HDL
- Cholesterol esters from HDL to VLDL and LDL
c) Enables HDLs to stay in circulation to remove cholesterol
