Lipipd Transport Flashcards
Why must lipids be transported bound to carried in the blood?
They are hydrophobic/insoluble in water
How are the majority of lipids transported in the blood?
Via lipoprotein particles
What do lipoproteins usually consist of?
Phospholipid
Cholesterol
Cholesterol esters
Proteins
TAGs
What is normal plasma glucose levels?
5mmol/L
What is the normal amount of cholesterol in blood plasma?
Less than 5mmol/L
Describe the structure of phospholipids
2 non polar hydrophobic fatty acid tails
Polar hydrophilic phosphate head
What are the functions of cholesterol?
Regulates membrane fluidity
Precursor of corticosteroids (steroid hormones)
Precursor of bile acids
What form is cholesterol transported in around the body?
As cholesterol ester
What enzyme catalyses the formation of cholesterol esters?
LCAT
Describe the structure of a lipoprotein
Phospholipid monolayer with small amount of cholesterol
Peripheral Apolipoproteins on outside of phospholipid monolayer
Integral apolipoproteins embedded in phospholipid monolayer
Cargo inside lipoprotein = TAG, cholesterol ester, fat soluble vitamins
Give 2 examples of integral apolipoproteins
ApoA
ApoB
Give 2 examples of Peripheral Apolipoproteins
ApoC
ApoE
How are lipoproteins classified?
By density
What are the 5 classes of Lipoproteins?
Chylomicrons
VLDL
IDL
LDL
HDL
What is the function of Chylomicrons and VLDLs?
Transport TAG
Where do Chylomicrons transport Triacylglycerols from and to?
Dietary TAG from the small intestine to adipose tissue
Where do VLDLs transport Triacylglycerols from and to?
TAGs synthesised in the liver to adipose tissue
What is the function of IDLs, LDLs and HDLs?
Transporting cholesterol
Where does IDLs and LDLs transport chosterol from and to?
Cholesterol synthesised in the liver to tissues requiring cholesterol
What is IDL in relation to LDL?
A short lived precursor of LDL
Where do HDLs transport cholesterol from and to?
From cholesterol laden tissues back to the liver to be metabolised to bile salts for excretion
What are Apolipoproteins?
They are the particular complement of associated proteins to a lipoprotein particle
What are the 2 roles of apoproteins?
Structural - packaging water insoluble lipids
Functional - act as ligands for cell surface receptors, Co factors for enzymes
What Apolipoprotein is added to Chylomicrons containing TAGs before they enter the lymphatic system?
ApoB(-48)
Once Chylomicrons containing TAGs enter the blood, what 2 apoproteins are added?
ApoC
ApoE
What is lipoprotein lipase?
Enzyme which breaks down TAG in lipoprotein particle to release fatty acids
Which Apolipoprotein on Chylomicrons binds to Lipoprotein Lipase on adipocytes and muscle ?
ApoC
Wha happens to ApoC when the TAG content of a Chylomicron has been reduced to about 20%?
ApoC dissociates
Leaves Chylomicron remnant
What happens to Chylomicron remnants?
Return to liver
ApoE binds to LDL receptor
Chlyomicron remnant taken up by receptor mediated endocytosis
What Apolipoproteins are added to VLDL when in the blood?
ApoB
ApoC
ApoE
What happens to VLDL when it reaches the endothelial cells in muscle and adipose?
Binds to lipoprotein lipase
Fatty acids released and are taken up by muscle for energy production, in adipose fatty acids re synthesised into TAG for storage
How do cells that need cholesterol obtain cholesterol?
Express LDL receptor and when LDL binds it takes it up via receptor mediated endocytosis
Why are LDLs not efficiently cleared by the liver? (Have the longest half life)
Do not have ApoC or ApoE
Liver LDL receptor has a high affinity for ApoE
What is the clinical relevance of high levels of LDL?
LDL susceptibility to oxidative damage due to its long half life
Oxidised LDL taken up by macrophages forming foam cells in intima of blood vessel
Foam cells form fatty streaks contributing to the formation of atherosclerotic plaques
Leads to atherosclerosis
What are the 6 classes of Hyperlipoproteinaemias?
I
IIa
IIb
III
IV
V
What are the clinical signs of Hypercholesterolaemia?
Xanthelasma
Tendon Xanthoma
Corneal Arcus
What happens in hypercholesterolaemia?
Cholesterol gets deposited in various areas of the body
What is Xanthelasma?
Yellow patches on eyelids
What is Tendon Xanthoma?
Nodules on tendon
What is corneal arcus?
Obvious white blueish circle around eye
What happens when an atherosclerotic plaque grows and then ruptures?
Blood flow is reduced
Once ruptured thrombosis occurs causing clotting
Leads to stroke or myocardial infarction
How are Hyperlipoproteinaemias initially treated?
Diet - reduce cholesterol and increase fibre
Lifestyle - more exercise, stop smoking
What is the next step if the initial approach to treating Hyperlipoproteinaemia doesn’t work?
Statins - inhibit HMG-CoA REDUCTASE so inhibit cholesterol synthesis
Bile salts sequestants- more bile salts makes liver use up more cholesterol by producing more bile acids
