L4 - Lipid Transport Flashcards
2% of lipids are transported in the blood attached to albumin, the rest are carried as what?
lipoproteins
What is the recommended range for plasma cholesterol?
<5mMol/L
Some cholesterol is obtained from the diet but most is synthesised in the liver. List three major functions of cholesterol
- Modulates membrane fluidity
- Precursor of steroid hormones
- Precursor of bile acids
Give some lipids that are transported within the micelles of lipoproteins
triglycerides/cholesterol esters (transportable form)/Fat soluble vitamins (A,D,E and K)
lipoproteins consist of three major things, a phospholipid monolayer, it’s cargo (lipids) and apoliporproteins which bind the lipids. These apolipoproteins can be peripheral or ______
integral
What do chylomicrons transport specifically around the bloodstream?
dietary fats
VLDL’S transport fats made in the liver, as they travel around the bloodstream and deplete their cargo they become IDL’s and then _____
LDL’s
what do HDL’s do?
transport cells excess cholesterol to the liver
How long are chylomicrons present for after eating a meal?
4 hours
Order these in DENSITY, highest to lowest chylomicrons idl's ldl's hdl's vldl's
HDL's LDL's IDL's VLDL's Chylomicrons
Which lipoproteins express apoB and which express apoA1? (important)
apoB - VLDL, IDL, LDL apoA1 - HDL
Give two functions of the apolipoproteins
- package lipids
- act as co-factors for enzymes
- act as ligands for cell-surface receptors
Chylomicrons containing dietary fats are loaded with cargo and the apoB-48 apolipoprotein in the small intestine before entering the lymphatics. Briefly describe their path from here to their breakdown in the liver
Enter the subclavian vein via the thoracic duct into the circulation and acquire ApoC and ApoE.
ApoC binds LDL on tissues and muscle, this releases the fatty acids and when triglyceride levels reach 20% apoC dissociates and the chylomicron becomes a remnant
Remnants travel to liver where LDL receptors on heptaocytes binds apoE and the remnant resulting in endocytosis and metabolism of the remnant
VLDL’s transport fat made in the liver, they also deliver them by binding binding to LPL on liver and muscle cells, what apolipoproteins are added to VLDL’s ?
apoB100 during formation
apoC and apoE from HDL particles in the blood
What are fatty acids released from any of these lipoproteins used for in the
a) muscle
b) adipose tissue
a) energy production
b) re-synthesis of triglyceride and storage as fat
As VLDL particles are depleted they can dissociate from LPL and go back to the liver, as they deplete to 30% they become IDL’s and then to 10% LDL’s. What do IDL’s lose to become LDL’s and are endocytosed by peripheral cells
apoC and apoE - explanation - this means they can no longer be cleared by the liver
What is the primary function of LDL’s?
To provide cholesterol from the liver to perihperal tissues
Why are LDL’s considered more dangerous?
They have a much higher half life in the plasma, this means that they are in the blood for longer and thus more susceptible to oxidative damage
How does oxidative damage to LDL’s lead to atherosclerosis?
Oxidised LDL’s are phagocytosed by macrohpages which results in the formation of foam cells -> fatty streak formatino -> atherosclerotic plaque formation -> atherosclerosis -> angina/stroke etc.
Why do we see fatty liver in patients with kwashiokor
Low protein diet means that lipoproteins can’t be made effectively, fats not delivered to tissues and instead retained in the liver
cells requiring cholesterol express what receptor on their surface?
LDL receptor- apoB-100 on LDL acts as the ligand for this
Nascent HDL’s accumulate cholesterol and phospholipids lining blood vessels, transfer to HDL’s requires enzymatic activity, true or false?
False, it does not require enzymatic activity
HDL’s collect cholesterol via reverse cholesterol uptake and deliver to the liver for breakdown to bile salts, they can also exhange cholesterol with LDL’s in circulation, and give to cells that need extra cholesterol T/F
T
What is a hyperlipoproteinaemia?
Raised plasma level of one or more lipoprotein classs
What causes hyperlipoproteinaemias?
Over-production or under-removal of the lipoproteins
A patient presents with chylomicrons in their plasma after fasting for 10 hours, what is defective?
LPL - they aren’t being depleted of their cargo (type 1 hyperlipoproteinaemia)
A patient presents with raised IDL and chylomicron remnant levels, what is causing this?
Defective apoE for removal in the liver
Clinical signs of hyperlipoproteinaemias are the result of cholesterol depositions in the body because of subsequent elevated cholesterol levels, name two of these clinical signs
Xanthelasma - yellow patches on eyelids
Tendon Xanthoma - Nodules on tendons
Corneal arcus - white circle around eye in younger people (present in normal older people)
give a non-pharmacological and a pharmacological approach to treating hyperlipoproteinaemias
non - Low cholesterol diet/ increase exercise/ stop smoking
pharm - bile salt sequesterants - forces live to make more bile acids which uses cholesterol/statins
