Atherosclerosis 2 Flashcards
Does VLDL and remnant particles contain much TAG?
They are TAG-rich
What is the Fuel Transport Pathway ?
- Chylomicrons transport TAG to periphery cells, remnants metabolised in liver
- VLDLs transport fuel from liver to peripheral tissues & remnants return to liver
- Part of the VLDL remnants & IDL are converted into LDL which enters the overflow
pathway
What is the Overflow pathway ?
- LDLs travel in blood from liver to the peripheral tissues and back to the liver
- On their way back they may enter the arterial wall
What can remove TAGs from TAG-rich lipoprotein particles ?
- Hydrolases
- Lipoprotein lipase (LPL)
- Hepatic triglyceride lipase
(HTGL)
What does the LPL do ?
- Digests TAGs in chylomicrons and VLDLs and releases FA & glycerol
for cell metabolism or storage - Also, bind to heparan sulfate proteoglycans on vascular endothelial cells
What is HTGL associated with ?
HTGL is associated with liver plasma membranes and acts on particles already digested by LPL
What can humans not metabolise in terms of the structure of the cholesterol?
Humans cannot metabolise the cholesterol ring system
What is involved in the reverse cholesterol transport ?
- CERP (cholesterol efflux regulatory protein)
- plays major role in cholesterol efflux - LCAT (lecithin:cholesterol acyl transferase)
- esterifies cholesterol - CETP (cholesterol ester transfer protein)
- a plasma protein
- transfers part of its cholesteryl esters to TAG
rich lipoproteins
- Binds to scavenger in liver after increasing in size
- Results in transfer of cholesterol to the cell
membrane, which is then excreted as free sterol
or as bile acids
Why are Apolipoproteins important for lipoprotein transport ?
- Solubilise the non-polar lipids in the circulation
- Interact with cellular receptors, therefore determine metabolic fate of lipoprotein
What is ApoE synthesised by and involved in ?
- Synthesised by the liver, brain, adipose tissue, and arterial wall
- Most abundant in plasma lipoproteins derived primarily from the liver i.e. VLDL and LDL
- Involved in the homeostasis of triacylglycerol-rich lipoproteins and HDL
In humans, ApoB48 is produced only in ?
The small intestine in response to fat in the diet
What is required for proper folding of ApoB proteins ?
Cholesterol esters
Only ApoB100 binds to?
ApoB specific receptors
What does ApoB-100 control vs ApoB-48 ?
ApoB-100 controls metabolism of LDL whereas ApoB-48 controls chylomicrons
ApoE controls ?
Receptor binding of remnant particles
ApoC act as ?
Enzyme activator/inhibitor & is extensively exchanged between different lipoprotein classes
What are key determinants for VLDL and LDL formation?
ApoB100 and ApoE
What happens without ApoB100 ?
- Much less CHY, VLDL and LDL are formed and the plasma TAGs and cholesterol
concentrations decrease as a result
What is Hypothyroidism ?
- An underactive thyroid gland
- Common signs are tiredness and weight gain
- Present in 1.4% to 13% of patients with hyperlipidemia
- Overt hypothyroidism is a secondary cause of hyperlipidemia and associated coronary heart
disease - Cholesterol profiles may be improved by treating overt hypothyroidism
The lipid abnormalities seen with hypothyroidism are thought to be primarily related to ?
A reduction in LDL receptor activity
Thyroid stimulating
hormone (TSH) might up-regulate ?
Hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) expression, which suggested a potential direct role of TSH in the cholesterol biosynthesis in the liver
What can smoking do to the vessels, cholesterol levels and blood pressure?
- Smoking can damage and tighten blood vessels, raise cholesterol levels, and raise blood pressure
- Smoking also doesn’t allow enough oxygen to reach the body’s tissues
