Lipid Transport Flashcards
What are the three lipid transport systems?
Exogenous
Endogenous
??
What is the function of the exogenous lipid transport system?
Transport lipids from the gut to the liver
What is the function of the endogenous lipid transport system?
Lipids synthesised by the liver to non- hepatic tissues include including adipocytes
Give the makeup (inc percentage) of fatty acids in circulation
Triglycerides(45%)
Phospholipids (35%)
Cholesterol (15%)
Free fatty acids (5%)
What are free fatty acids formed from?
Triglycerides stored in adipose tissue
What do free fatty acids circulate with?
Bound to protein as an Na+ salt - particularly albumin
What would an unbound fatty acid act as in the fluid?
A detergent
What does saturation of FA molecules occur at?
2mM
How do fatty acids enter cells?
Simple diffusion
What are lipoproteins carried in the blood as?
Plasma lipoproteins
What are the 5 types of lipoprotein?
Chylomicron Very low density lipoprotein (VLDL) Intermediate density lipoprotein (IDL) Low density lipoprotein (LDL) High density lipoprotein (HDL)
What does the hydrophobic core consist of?
Triglycerides and cholesterol esters
What does the hydrophilic surface consist of?
Phospholipids and cholesterol
What’s the difference between an apolipoprotein and a lipoprotein?
Lipoprotein = particle Apolipoprotein = associated with the lipoprotein
What apoproteins do chylomicrons have?
B48, APOCII, E
What apoproteins do VLDL have?
B100, APOCI, APOCII, APOCIII and E
What apoproteins do LDLs have?
B100
What apoproteins do IDLs have?
B100 and APOE
What apoproteins do HDLs have?
APOAII, APOAII, APOCII, APOCIII, APOD and APOE
Give functions of apoproteins
Structural
To solubilise lipids
Act as enzyme cofactors
Tissue targeting
What are the enzymes or enzyme cofactors for lipoprotein lipase?
APOCII
Which apoproteins bind to LDL receptors?
Apo B100 and APO E
Which apoproteins bind to HDL receptors?
APOE
How do dietary lipids enter the gut?
Triglycerides
What does lipase break down triglycerides into?
Fatty acids and monoacylglycerol
What do phospholipids and cholesterol esters form?
A chylomicron which only expresses APOB48
What do nascent chylomicrons interact with?
A HDL and picks up Apo CII and Apo E
Where is the B48 added to the chylomicron?
SER
How are chylomicrons secreted in the lymphatic system?
Reverse pinocytosis
Where do chylomicrons get their Apo C2, C3 and E from?
HDLs
How does the chylomicron undergo enzymatic degradation?
Interaction with lipoproteinlipase
Where is lipoproteinlipase b mainly expressed
Tissues which mainly metabolise lipids (like muscle, adipocytes and mammary glands)
How does the Km of LPL isoform in adipocytes compare to the Km in muscle?
Greater in adipocytes
What is LPL activated by?
APO CII
What is LPL on adipocytes stimulated by?
Insulin
What is type 1 hyperlipidaemia?
Deficiency in lipoproteinlipase or apo C2
What is type 1 hyperlipidaemia characterised by?
High plasma triglyceride
What is type 2 hyperlipidaemia?
Caused by a genetic defect in the synthesis, processing or function of the LDL receptor v
What is type 2 hyperlipidaemia characterised by?
High LDL levels
What is type 4 hyperlipidaemia?
Raised VLDL concs often due to obesity or alcohol abuse
Why do chylomicrons have a low density?
High TG levels
What fat soluble vitamins do chylomicrons contain?
A and E
What is a chylomicrons lifetime in circulation?
1 hour
What is a triglycerides lifetime in circulation?
5 mins
How are remnants of chylomicrons and VLDLs removed by the liver?
With the involvement of APO E
When are VLDLs synthesised?
When the dietary intake of carbs exceeds immediate needs
What are the components of nascent VLDLs?
TG, fatty acids, phospholipids, cholesterol esters and APO B100
What is the formation of VLDLs stimulated/ inhibited by?
Stimulated by insulin and inhibited by glucagon
What molecules interfaces with and activates LDLs?
Apo CII
What are foam cells?
Part of the initiating process of atherosclerotic cells within the blood vessel
What happens when the products of a TG travel into an adipocyte cell?
They will be converted back into TGs and stored
What happens when the products of a TG travel into an muscle cell?
Converted into ATP, o2 and water
What happens when the TGs are removed from an LPL?
Becomes an IDL
How much IDL will be transported into the liver?
60%
What happens when IDLs interact with HDLs?
The HDLs take back the apo E and apo CII for future donations
How much of the LDL is returned to the liver?
60-70%
What happens when Apo B100 attaches to the peripheral tissue
Fatty acids, cholesterol, glycerol and amino acids are broken down and used in metabolism
What happens if the LDL circulates for long enough?
It undergoes oxidation
What happens if the macrophage accumulates too much oxidised LDL?
Forms a foam cell
How long does it take for LDLs to be metabolised?
3 days
What do HDLs do?
Takes cholesterol laden cells back to the liver
What are the three ways in which HDLs can be made?
As nascent particles by the liver and intestine
Budding or apoproteins from chylomicrons
Free from apoA1
What do nascent HDLs do?
Acquires cholesterol and phospholipids from endothelial cells
What does the transfer of cholesterol and phospholipids from nascent HDLs require
ATP binding cassette protein 1 (ABC1)
What does HDL possess that catalyses cholesterol esterification and what does it prevent?
Lecithin cholesterol acyltransferase (LCAT) prevents it returning to the cell
What do Cholesterol rich HDLs do?
Delivers it to the liver or exchange it with other particles including VLDL and VLDL remnants
What is the healthy HDL:LDL ratio
3:5
Give the steps of receptor mediated endocytosis
LDL binds to the LDL receptor on the plasma membrane
The membrane invaginate and forms an endosome
Inside the endosome the LDL and receptor dissociates
Receptors is then broken down after fusion with a lysosome
What is an LDL broken down into?
Amino acids
Fatty acids
Cholesterol ester droplets
What happens to the cholesterol ester droplets after they’ve been broken down from LDLs
Reforms cholesterol which is incorporated into the ER or can be used to synthesise steroid hormones
What regulates cholesterol uptake and synthesis?
Cholesterol regulates itself
What happens if there’s an increase in cholesterol?
Inhibits HMG-CoA reductase activity
What happens if there’s a decrease in cholesterol?
Increases LDL receptor synthesis and expression
Where do you find SR-81?
Endothelial cells, intestine, macrophages, smooth muscle cells, keratinocytes etc etc
What does SR-81 bind to?
HDL
What does SR-A1 and SR-A2 bind to?
LDL
Where do you find SR-A1 and SR-A2?
Macrophages
What is the cause of familial hypercholesterolemia?
Single amino acid substitution that prevents localisation of the LDL receptor to the coated pits
What happens in familial hypercholesterolemia?
LDL receptors don’t bind to LDL enough
Too much LDL in blood
Build up in cholesterol leads to the formation of a foam cell
Foam cells are the precursors for atherosclerosis
What is high serum cholesterol?
800mg/ml
What is a normal cholesterol level?
200mg/ml
What happens to homozygous people with familial hypercholesterolemia?
Develop blocked arteries- die young from heart attacks
De novo synthesis is not regulated by LDL
What is diabetes mellitus?
Increased FFA mobilisation
Decreased chylomicron and VLDL utilisation
What does obesity cause?
Hypertension
NIDDM
Hyperlipademia
Hyperglycaemia
What gene defects in receptors lead to?
Hypercholesterolemia
Atherosclerosis
