1. Lipid Transport Flashcards
1
Q
Where do lipids come from in the blood?
A
Either from out food (exogenous), or they’re made by our liver (endogenous)
2
Q
What are lipoproteins?
A
- lipid delivery vans
- they transport cholesterol and triglycerides
3
Q
What are triglyceride-rich lipoproteins? And what is their composition?
A
Chylomicrons
- 90-95% TG
- very small amounts of cholesterol esters, PLs, free cholesterol and proteins
- get from diet
VLDL
- 50-65% TG
- 5-10% protein
- a bit more of everything else than CMs
- produced by liver
4
Q
What are cholesterol-rich lipoproteins? What os their composition?
A
LDL
- 5-6% TG
- 25% protein
- Much more cholesterol ester (35-45%)
- also more of the other components
HDL
- 7% TG
- 45% protein
- less cholesterol esters and free cholesterol than LDL, similar PL levels
5
Q
What are apolipoproteins? Give examples
A
They have various roles
- structural component of lipoproteins
- ligand binding receptor recognition
- activation/inhibition of lipolysis
- cholesterol efflux
- polymorphic forms
- some have undefined role
- They govern lipoprotein metabolism
- ApoB is major apolipoprotein of VLDL, IDL and LDL
- ApoB48 - only in lipoproteins of intestinal origin (exclusive to CMs and remnants)
- ApoA1 - major apolipoprotein of HDL
- ApoA,C and E move between HDLs and TG-rich lipoproteins
6
Q
What is the exogenous lipoprotein pathway?
A
Delivers TGs FROM THE GUT to adipose tissue and muscle, and cholesterol to the liver
- dietary fat and cholesterol are packaged into CMs, along with cholesterol and bile acids from liver
- CMs pass through capillaries
- LPL on endothelial walls will hydrolyse CMs for storage and use
- FFAs from this hydrolysis goes to muscles (oxidised) and adipocytes (stored)
- remnant lipoprotein goes to the liver and acts on LDL (and related) receptors on liver and is taken up
7
Q
What is the endogenous lipoprotein pathway?
A
This delivers TGs and cholesterol FROM THE LIVER to adipose tissue, muscle and other tissues
- liver synthesises cholesterol - packages with ApoB100
- TG is then added
—This becomes VLDL - VLDL travels in circulation, is broken down by LPL —> IDL and nascent HDL
- IDL acts on liver receptors (LDLR and LRP)
- It will also be acted on by hepatic TG lipase (HTGL), which hydrolysis it further to LDL
- This LDL can act on peripheral receptors, as they cannot make cholesterol themselves
8
Q
How are LDL receptors recycled?
A
- LDL binds to its receptor
- it is then internalised into an endosome
- in this, there is an acidic environment, causing LDL to be released from the receptor, and the receptor can travel back up to the surface and be presented again
9
Q
What does PCSK9 do to stop recycling of LDLR?
A
- PCKS9 binds to the LDL-receptor complex and prevents LDL release
- therefore increased PCSK9 causes a reduction in LDL receptors on the surface (as they get degraded in an endosome)
10
Q
What is reverse cholesterol transport?
A
- Any cholesterol left over in the tissues cannot be broken down, and so needs to be removed to avoid atherosclerosis
- ATP-binding cassette 1 (ABCA1) takes it out of the cell and into HDL
- HDL exchanges material with circulating IDL, and reduces cholesterol inside
- IDL then acts on LDLR and LRP on liver
- HDL will also act on the SR-B1 receptor on the liver
11
Q
What controls cholesterol homeostasis?
A
- Cholesterol produced in multi-step process - rate limiting step is HMG-CoA reductase (HMG-CoA to mevalonic acid)
- cholesterol can be excreted with biles acids, or mixed with ApoB and TGs to make VLDL
- SREBP2 is very sensitive sterol sensor protein - senses intrahepatic free cholesterol
- increased SREBP2 —> decreased cholesterol synthesis
- Also downregulates the LDL receptor, so less LDL is taken to the liver
12
Q
What happens in combined Hyperlipidaemia?
A
- High amounts of free cholesterol —> more VLDL
- causes saturation of LPL, and thus more remnant particles and IDL
- more exchange of cholesterol from HDL to IDL, depleting HDL
- more lipoproteins returned to liver via LDLR
- some is hydrolysed by HTGL, and so more cholesterol ends up in the tissue
- accumulation of cholesterol —> atherosclerosis risk
13
Q
What do oxidised lipoproteins do?
A
- when all pathways are saturated, there will be remnant particles hanging around for longer
- these become susceptible to enzymes that normally wouldn’t have any action on them —> oxidation
- These are a chemoattractant for macrophages, and so increases inflammation
- the macrophages can also become foam cells
14
Q
What is the process of atherosclerosis?
A
- Fatty streak formed by foam cells and intercellular lipids inside the vessel wall
- plaque formation —> fibrous cap with collagen fibres
- unstable plaque —> complicated lesion, thrombosis and ulceration
