Lipoprotein Handling Flashcards
Name the two pathways by which lipoproteins can be formed?
Endogenous (made by liver in the form of VLDL) or exogenous (from dietary sources, transported in chylomicrons post-absorption in the intestines)
Describe the endogenous pathway of lipoprotein synthesis
VLDLs transport endogenously synthesised TAG from the liver to the tissues
Describe the exogenous pathway of lipoprotein synthesis
Chylomicrons transport dietary lipids, that have been absorbed by the intestine, to the tissues.
Describe the general structure of lipoprotein
Cholesterol esters and TAG are located in the hydrophobic core and the outer layer contains phospholipids, free cholesterol and apoproteins
When does endogenous fatty acid synthesis usually occur?
In the presence of excess energy intake, where fatty acids are combined with glycerol-3-phosphate to form TAG
What is the most abundant form of lipid in the body?
TAG (90% of fatty acids go on to form this)
Why does the transport of TAG require modification to become lipoprotein?
TAG is hydrophobic and therefore can’t be transported in aqueous blood so it is packaged into lipoproteins to enable transport
What role do apoproteins play in lipoproteins?
Control the fate of the lipoproteins by interacting with cellular receptors as well as playing a role in activating and inhibiting enzymes
Name the 5 different types of lipoprotein in order of density, from lowest to highest.
Chylomicron, VLDL, IDL, LDL, HDL
What is the main component of chylomicron and what is it’s main apoprotein?
Main component = TAG.
Main apoprotein = B48
What is the main component of VLDL and what is it’s main apoprotein?
Main component = TAG
Main apoprotein = B48
What is the main component(s) of IDL and what is it’s main apoprotein?
Main components: TAG and cholesterol
Main apoprotein = B100
What is the main component of LDL and what is it’s main apoprotein?
Main component: cholesterol
Main apoprotein: B100
What is the main component of HDL and what is it’s main apoprotein(s)?
Main component: protein
Main apoproteins: AI, AII
What is the role of the B100 apoprotein?
controls the metabolism of LDL
What is the role of the B48 apoprotein?
controls chylomicrons
What is the role of the ApoE apoprotein?
controls receptor binding of receptor particles
What is the role of the ApoC apoprotein?
acts as enzyme inhibitor
What is the function of chylomicrons?
Transport dietary TAG
What is the function of VLDLs?
Transport TAG from liver to the periphery
How are IDLs formed?
From the shrinking of VLDLs into a remnant particle (IDL)
How are LDLs formed?
From the conversion of IDL particles to LDL particles in the liver
What is the function of LDL?
Mainly contain esterified cholesterol which they deliver to the peripheral tissues
What is the function of lipoprotein lipase?
Degrades TAG in chylomicrons and VLDL to release FFA and glycerol for uptake by adjacent cells.
Describe lipoprotein lipase activity after a meal
LPL activity high in adipose tissue
Describe lipoprotein lipase activity during starvation
LPL activity high in muscle so fatty acids derived from VLDL are mainly fed into oxidation (to release energy)
Which enzyme converts IDL to LDL?
hepatic TAG lipase
Why may cells take up LDL?
if intracellular cholesterol levels decline (only if reactions to make cholesterol cease)
How do cells take up LDL?
LDL (apoB/E) receptor on the plasma membrane of the cell whereby binding causes cholesterol to be released and esterified within the cell
Why is cholesterol essential?
Essential part of cell membranes and is a precursor for bile acids and steroids
Which transcription factor regulates the expression of HMG-CoA reductase and the LDL receptor?
SREBP
How may smoking/diabetes contribute to the formation of atheromatous plaques?
Oxidised LDL (free radical) generated which binds to scavenger receptor instead of LDL receptors in macrophages. Because these scavenger receptors take up cholesterol, and have no negative feedback system, the macrophages become laden with lipid and form foam cells which leads to the formation of fatty streaks in the arterial wall, leading to the formation of a plaque.
How do statins work to reduce blood cholesterol levels?
In the liver HMG-CoA reductase is an enzyme involved in cholesterol sythesis which is packaged into VLDL, statins inhibit this enzyme to reduce blood cholesterol levels
How does cholestryamine work to reduce blood cholesterol levels?
Binds bile acids in the gut to prevent enterohepatic circulation
Where are HDLs formed?
Liver and intestine
What is the role of HDL?
Scavenges free cholesterol from cell membranes via ABCA1 membrane transporter and esterifies this cholesterol. In addition, HDL transports cholesterol from the peripheral tissues to the liver for disposal as well as binding to scavenger receptors to transfer cholesterol to the cell membrane.
