Cholesterol & lipoproteins Flashcards
What are the functions of lipids
- energy storage
- cell memb. components
- solubilise fat soluble vitamins
- biosynthesis precursors
- signalling molecules
Where is cholesterol obtained from
- 25% diet
- synthesised in liver
How is cholesterol transplanted in blood
- insoluble in blood plasma
- lipoprotein carriers
- what are lipoproteins
Particles transporting lipids
What makes lipoproteins different
Protein:lipids
How are lipoproteins classified
- density
- chemical
What are the different classes of lipoproteins and where are they made
- chylomicrons (intestines)
- VLDL (liver)
- LDL (VLDL)
- HDL (blood)
What is the function of chylomicrons
- transport of dietary fats from intestines
What is the function of VLDL
Transport lipids to peripheral tissues
What is the function of LDL
- main carrier of chol.
- provides cholesterol to peripheral tissues
What is the function of HDL
- transport cholesterol to liver from peripheral tissues
What is the structure of lipoproteins
- monolayer—> phospholipids, cholesterol and apolipoproteins
- core—> cholesterol esters, triglycerides
What are apolipoproteins
- protein strands
- surface of lipoproteins
What is the function of apolipoproteins
- determine start + end points for cholesterol transport
What makes lipoproteins
Lipid + apolipoproteins
What are the 4 major classes of apolipoproteins
- ApoA
- ApoB
- ApoC
- ApoE
Where is ApoA found and what is its function
- HDL
- mediates efflux of cholesterol from peripheral cells
- influx in liver
Where Ishtar function of ApoB
- recognises ApoB/E receptors
- facilitates LDL uptake
What is the function of ApoC
- activator of lipoprotein lipase
What is the function of ApoE
- stabilise VLDL
- ligand for ApoB receptor
What is the synthesis of apolipoproteins in the small intestines regulated by
- dietary fat intake
What is the apolipoproteins liver synthesis controlled by
- drugs
- hormones
Give 2 examples of apolipoproteins function
- regulate key enzymes in lipoproteins metabolism
- ligand for interaction with lipoprotein receptors
Give examples of apolipoproteins regulating key enzymes
- ApoC-ii —> lipoprotein lipase
- ApoA-i lecithin-cholesterol acyltransferase
Give examples of ligand interacting with lipoprotein receptors
- apoB100 & ApoE in LDL receptors
- ApoA-i for HDL receptors
what is the structure of LDL
- phospholipids & free colesterol on SM
- hydrophobic core –> triglyceride & cholestryl esters
- ApoB
what is the structure of HDL
- SM (same as LDL)
- core (same as LDL)
- Apo A-I
- Apo A-ii
what is the function of ApoA-i and Apo-Aii in HDL
- protect against oxidation
- anti-inflammatory
where are chylomicrons made & what do they do
- intestine
- transport triglycerides & cholesterol in blood
what are triclycerides hydrolysed by and what are they used for
- lipoprotein lipase –> fatty acids
- energy source/store
what happens to chylomicrons after hydrolysis of triglycerides
- shrink
- back to liver
where are VLDL made? what do they do? why does lipoprotein lipase act on them
- liver
- transport lipids to tissue
- release fatty acids for tissues
what happens to LDL from VLDL
- taken up by target cells
- by LDL receptors
- digested in lyssome
- release cholesterol
what is the function of HDL? where are they synthesised?
- remoce cholesterol
- blood
what are lipoprotein receptors
membrane-bound receptors
what is the function of lipoprotein receptors
- enable enterance of cholesterol to cells
what does LDL receptor bind to
- apoB-100
- apoE
what is LDL receptor gene expression regulated by
- intracellular cholesterol concentration
what do high levels of intracellular cholesterol result into
- supress LDL receptor synthesis
- chol not taken up by cells, remain in blood
- deleterious onsequences
how does HDL protect aganst arthesclorisis
- scavenges cholesterol back to liver, excerted by bile
- reverse Cholesterol Transport
what is dyslipidaemias
- familial hypercholesterolaemia
- mutation in LDL receptor
- cells can’t take up LDL
what does dyslipidaemias result in
- blood LDL increases
- excess cholesterol in arteries
- higher risk of atherosclerosis
what is cholesterol essential component of
- cell membranes
- bile acids
- steroid hormones
- fat-soluble vitamins
what do high serum levels indicate
- risk of cardiovascular disease
what are the cardiac clincal manifestations of artherosclerosis
- chest pain
- palpitations
- heart attck
what are the cerebral clinical implications of atheroscllerosis
- stroke
- cerebral haemorrhage
what are the peripheral clinical implications of athersclerosis
- pain
- ischaemia
- ulceration
- gangrene
what are the stages of development of athresclerosis plaque
- fatty streak
- fibrous plaque
- advanced plaque
what is the cholesterol-synthetic pathway
- HMG-CoA –> Mevalonate –> IPP –> FPP –> squelene –> cholesterol
what is the enzyme converting HMG-CoA to mevalonate
HMG-CoA
how do statins reduce the risk of hypercholestrolaemia
- prevent cholesterol synthesis in liver
- act as HMG-CoA reductase inhibitors –> no mevalonate
what are pleitropic effects
- unanticipated
- undesirable
what are FPP & GGPP
isoprenoids
how are Ras & Rho prenylated
- Ras: Farnesylated (FPP)
- Rho: Geranylgeranylated (GGPP)
what are statins’ pleitropic effects
- improve endothelial dysfunction
- antioxidant
- inhibit iflammatory response
- stabilise artherosclerotic plaques
what are PCSK9 expressed by
- liver
- intestine
what is the role of PCSK9
- lipid metabolism
- promote intracellular degenaration of LDL-R
- prevents recycling of LDL-R to cell surface
- reduces LDL-R population
what does PCSK9 inhibition do
increase LDL uptake
