Cholesterol and Lipid Metabolism Flashcards
What are 3 main features of lipids?
insoluble (or partially soluble) in water
essential for membrane integrity and biogenesis
energy sources, precursors for hormones and signalling molecules
How are non-polar lipids transported?
in the blood as lipoproteins
Name 2 non-polar lipids.
cholesterol esters and triglycerides
What are the 2 classifications of lipoproteins?
HDL and LDL
Atherosclerosis is strongly associated with high HDL and low LDL.
True/False?
False
Elevated LDL
Decreased HDL
Esterified cholesterol and triglycerides make up which component of lipoproteins?
hydrophobic core
What makes up the hydrophilic coat of lipoproteins?
monolayer of amphipathic cholesterol, phospholipids & apoproteins
Which major lipoproteins contain apoB-100?
LDL and VLDL particles
Which major lipoprotein contains apoA1 and apoA2?
HDL
Cylomicrons contain apoB-48 and are the largest major lipoprotein.
True/False?
true
What are the roles of apoB-contiaing lipoproteins?
Deliver triglycerides to:
muscles for ATP synthesis
Adiopocytes for storage
Where are chylomicrons formed and which pathway are the involved in?
intestinal cells
exogenous pathway
Where are VLDL particles formed and which pathway are they involved in?
liver cells
endogenous pathway
Which type of triglycerides does the exogenous pathway transport?
dietary triglycerides
Which type of triglycerides does the endogenous pathway transport?
triglycerides synthesised in that organ i.e. the liver
What are the 3 steps in the life-cycle of ApoB-containing liposomes?
- Assembly & Activation
- Intravascular metabolism
- Receptor mediated clearance
What is MTP and what does it do?
Microsomal Triglyceride transfer Protein
Lipidates apoB100 to form VLDL which joins with triglyceride droplets
Where do the free fatty acids used in VLDL assembly come from?
adipose tissue - particularly during fasting
de novo synthesis
How are chylomicrons and VLDL particles activated?
transfer of apoCII from HDL particles
Where do VLDL particles assemble?
hepatocytes
Which lypolitic enzyme is associated with capillary endothelium?
Lipoprotein lipase (LPL)
What does ApoCII facilitate?
binding of chylomicrons + VLDL particles to LPL
What does LPL do to core triglycerides so that they can enter tissue?
hydrolyses them to free fatty acids + glycerol
What are chylomicron and VLDL remnants?
Particles depleted of their triglycerides, but still containing cholesteryl esters
What happens after the chylomicrons and VLDL dissociate from LPL?
ApoC II is transfered to HDL in exchange for ApoE - particles are now remnants
What is apoE?
a high affinity ligand for receptor mediated clearance
What do remnants do?
return to liver where they are further metabolised by hepatic lipase
What percentage of remnants are cleared by receptor mediated endocytosis into hepatocytes?
All of ApoB-48 containing remnants & 50% of apoB-100 containing remnants
What is clearance of LDL particles crucially dependent upon?
the LDL receptor expressed by liver and other tissues
Hepatocytes endocytose LDL particles by receptor-mediated endocytosis. What happens then within the cell?
cholesterol is released from cholesteryl esters by hydrolysis
What does this released cholesterol cause?
inhibition of HMG-CoA reductase
down-regulation of LDL receptor expression
storage of cholesterol as cholesteryl ester
What is HMG-CoA reductase?
the rate limiting enzyme in de novo cholesterol synthesis
