MEH - Lipid Transport Flashcards
How are lipids transported n the body?
98% bound in lipoprotein particles 2% albumin
What do lipoprotein particles consist of (5)?
TAGS, phospholipid, cholesterol, cholesterol esters, proteins
Above what level of cholesterol is a risk?
> 5mM/L
How are different phospholipids classified?
According to their different polar head groups
How much cholesterol do we require a day? What happens if we don’t get that from the diet?
Minimal or none. The liver can synthesise cholesterol directly (most is actually done this way)
3 uses of lipids in the body?
- Bile salts
- Steroid hormones
- Membranes
What is cholesterol transported around the body as? What enzyme catalyses the formation of these?
Cholesterol esters - LCAT
What are apolipoproteins? Which one is associated with bad cholesterol (LDL) , which with good (HDL)?
Specific proteins associated with lipoprotein particles - have functional and structural roles. Groups ABCDEH
ApoB- bad
ApoA1 - good
There are 5 distinct classes of lipoproteins - what are they? What varies in them? Which has the most of each
Chylomicrons, VLDL, LDL, IDL, HDL
They vary in fat content, cholesterol ester, apolipoprotein and cholesterol.
VDLD has most lipid in least protein
HDL has high protein and cholesterol ester content
Why is HDL the smallest in size and VLDL the largest?
Because particle diameter is inversely proportional to density
What are the structural (1) and functional (2) roles of apolipoproteins?
1) Packaging water insoluble lipid
1) cofactors for enzymes
2) ligands for cell surface receptors
What apolipoproteins are added to chylomicrons during their metabolism (3) ?
First ApoB-48 - then they enter lymphatic system
Once enter thoracic duct Apo C and E are added.
Apo C binds to LPL (lipoprotein lipase) on adipocytes and muscle - depletes lipoprotein content
Which receptor binds to ApoC and which to ApoE and where?
LPL - lipoprotein lipase binds to ApoC in skeletal muscle and adipose tissue so the chylomicron depletes it’s contents - when contents depleted to 20% it becomes a chylomicron remnant and ApoC dissociates
LDL - low density lipoprotein receptor in liver - binds to ApoE and the chylomicron remnant is taken up by hepatocytes by endocytosis - lysosomes then contain enzymes for remaining metabolism.
What is the role of lipoprotein lipase?
It is an enzyme that hydrolyses TAGS in lipoproteins - requires apoC as a cofactor - in endothelial cells in capillaries –> FA can then be taken in by skeletal muscle and adipose for use/storage.
What is the different roles of VLDL, LDL, IDL, and HDL?
VLDL - made by liver to transport TAG to other tissues
LDL - provide cholesterol from liver to other tissues
HDL - can remove cholesterol from laden cells and return it to the liver.
Why is LDL bad?
Doesn’t have apoC or ApoE so are not efficiently cleared by endocytosis and lysosomal degradation in the liver, so in the blood circulation longer and more susceptible to oxidative damage - radicals –> oxidised LDL can be taken up by macrophages forming foam cells that then add to atherosclerosis in blood vessels.
Which Apos do Chylomicrons, VLDL, LDL and HDL have?
Chylomicrons - first B-48 then C then E
VLDL - have apoB100, ApoC and ApoE
LDL - ApoB
HDL - ApoA
What is an IDL particle?
If the VLDL content depletes ~30% it becomes a short lived IDL particle before becoming an LDL particle (20% and loses Apo E and C).
What is an LDL receptor and what is its use? What is the ligand for this receptor on LDL?
Receptor expressed by peripheral cells that bind LDL - LDL take in via receptor mediated endocytosis to deliver cholesterol. Ligand is ApoB100
Where are HDLs synthesised (3)? What else can form a HDL-like particle? What happens as they mature? Is an enzyme required?
HDLs are synthesised in the liver and intestine, ApoAI can also acquire cholesterol and phospholipid from other lipoproteins and cell membranes to form a HDL like particle. HDLs can also be budded off from VLDL and chylomicrons as they are digested by LPL. They mature as core fills up with phospholipid and cholesterol from cells lining blood vessel - lipid transfer doesn’t need enzymes.
How does HDL reduce likelihood of foam cells and atherosclerotic plaque formation?
They remove cholesterol from laden cells in epithelium of blood vessels.
What protein within the cell facilitates transfer of cholesterol to HDL? How is cholesterol then converted to cholesterol ester?
ABCA1
LCAT
What happens to cholesterol in HDL (2)?
1) Cells requiring cholesterol for steroid hormone synthesis can scavenge from HDL using the scavenger receptor SR-B1
2) HDL can exchange cholesterol for TAG with VLDL using the CETP (cholesterol exchange transfer protein)
What is lipoproteinaemia? What causes it?
Raised plasma level of one of more lipoprotein classes. Either over production or under removal
What 3 defects cause lipoproteinaemias?
Enzymes
Receptors
Apoproteins
What receptor/apoprotein can be defective causing lipoproteinaemia?
- LDL receptor
- ApoE
How many types of lipoproteinaemia are there?
6 (I, IIa, IIb, III, IV, V)
Where in the body can cholesterol deposit and whats it called?
Eyes - corneal Marcus
Tendons - Xanthoma
Eyelids - Xanthelasma
Do you want low or high HDL relatively in the blood?
High - want low LDL
How do you treat high cholesterol?
Diet - mainly reduced Sat fats so cholesterol can’t be made. Reducing actual cholesterol may have limited effects.
Lifestyle - increase exercise stop smoking
Drugs - if no improvement
Bile salt sequestrants
Statins - block HMG co A reductase - e.g. atorvastatin
How do bile salt sequstrants reduce cholesterol? Name 1
Same as dietary fibre sequester cholesterol to be excreted. Colestipol
How do statins work and which part of the cholesterol synthesis pathway does this enzyme work at?
Block HMG co A reductase which is the first enzyme in the cholesterol synthesis pathway
What normal levels do you want LDL and HDL in blood?
HDL >1mmol/L (.1.2mmol/L women)
LDL < 3mmol/L
