Lipid transport Flashcards
why is it a problem to transport lipid in the blood
they are hydrophobic so need carriers
how are 98% of lipids transported in the blood
lipoprotein particles
how is 2% of lipids transported in the blood
bound to albumin
what is the range for total cholesterol in the blood
less than 5mmol/L
describe the structure of a phospholipid
- polar hydrophillic head
- non-polar hydrophobic fatty acid tails
what molecules are in the head of phospholipids
choline
phosphate
glycerol
what are the two classes of phospholipids and how do they differ
- phosphatidylcholine (choline in head)
- phosphatidylinositol (inositol in head)
what structures can phospholipids form
- liposome
- micelle
- bilayer
where is cholesterol obtained from
some from diet but mostly from liver
what is the role of cholesterol
membrane fluidity
precursor of steroid hormones
precursor of bile salts
what is cholesterol transported around the body as
cholesterol ester
how is a cholesterol esters made
cholesterol esterified with a FA using enzyme lecithin cholesterol acyltransferase (LCAT) or acetyl CoA cholesterol acyltransferase
describe the structure of a lipoprotein
- phospholipid monolayer with some cholesterol sphere
- filled with cargo of TAG, cholesterol esters, fat vitamins
- integral and peripheral apolipoproteins
what are the five classes of lipoproteins
- chylomicrons
- VLDL
- IDL
- LDL
- HDL
what are the main carriers of fats
chylomicrons
VLDL
what are the main carriers of cholesterol esters
IDL
LDL
HDL
order the classes of lipoproteins in terms in density from less dense to more dense
- chylomicrons
- VLDL
- IDL
- LDL
- HDL
what is the relationship between particle diameter to density
particle diameter inversely proportional to density
why can plasma have a creamy appearance
chylomicrons in plasma 4-6hrs after a meal
what are apolipoproteins
particular complement of associated proteins
what are the six major classes of apolipoproteins
A, B, C, D, E, H
what are the two roles of apolipoproteins
- structural: packaging water insoluble lipids
- functional: co-factor for enzymes and ligands for cell surface receptors
what class of apolipoproteins are important to CM, VLDL, IDL, LDL
apoB
what class of apolipoproteins are important to HDL
apoA1
where are chylomicrons loaded
small intestine
what apolipoprotein is added to chylomicrons
apoB-48
where do loaded chylomicrons travel to
lymphatic system and drain into thoracic duct which empties left subclavian vein
what two new apolipoproteins are acquired by chylomicrons when draining into throacic duct into blood
apoC and apoE
how are fats in chylomicrons depleted
apoC binds to lipoprotein lipase (LPL) on adipocytes and muscle capillary walls and muscles use fat for energy and adipose store FA as TAG
what happens to a chylomicron when it is reduced to 20%
apoC dissociates and chylomicron becomes a chylomicron remnant
what happens to chylomicron remnants
travel back and taken up by liver using receptor mediated endocytosis by apoE binding to LDL receptor on hepatocyte where remainder of contents used for metabolism
what does the enzyme lipoprotein lipase do
hydrolyses TAG in lipoproteins
what is the function of chylomicrons
transport dietary TAG from intestine to tissues
what is the role of VLDL
transport TAG in liver to adipose
what is the role of IDL
short lived precursor for LDL
transport cholesterol from liver to tissues
what is the role of LDL
transport cholesterol from liver to tissues
what is the role of HDL
transport excess tissue cholesterol to liver for disposal as bile salts
where is VLDL made
liver
what apolipoprotein is added to VLDL during formation
apoB100
what apolipoprotein is added to VLDL during travel in blood
apoC and apoE from HDL
where does VLDL bind and what occurs
lipoprotein lipase on endothelial cells in muscle and adipose and start to become depleted of TAG
- muscle uses FA for energy
- adipose storage
how are IDL and LDLs formed
VLDL –> IDL –> LDL
what percentage depletion of VLDL does it become IDL
30%
what happens to IDL particles
can either taken up by liver or rebind to LPL enzyme for further depletion
what percentage depletion of IDL does it become LDL and what happens to the IDL
10%
- apoC and apoE dissociate
what is the primary function of LDL
provide cholesterol from liver to peripheral tissues
how do peripheral tissues take up fats from LDLs
peripheral cells express LDL receptors and take up LDL via receptor mediated endocytosis
why are LDLs not effectively taken up by liver
LDL do not have apoC or apoE and liver LDL receptor has high affinity for apoE
why is LDL more damaging than others
longer half life so more susceptible to oxidative damage
- oxidised LDL take up by macrophages that can transform to foam cells which can lead to atherosclerotic plaques
describe the process of LDLs entering cells through receptor mediated endocytosis
- cells requiring cholesterol express LDL receptors on mem
-apoB100 on LDL acts as a ligand for receptors - receptor-LDL complex taken into cell by endocytosis into endosomes
- fuse with lysosomes for digestion to release FA and cholesterol
- LDL receptors on cells controlled cholesterol conc in cell
where are HDLs synthesised
- liver and intestine
- can bud off chylomicrons and VLDL as they are digested by LPL
- free apoA-1 can also acquire cholesterol and phospholipid from other lipoproteins and cell mems
how doe HDLs mature
- accumulate phospholipids and cholesterol from cell lining blood vessels
- hollow core fills and takes globular shape
-does not require enzymatic activity
what is reverse cholesterol transport
- HDLs have ability to remove cholesterol from cells with high cholesterol to return to liver
- important to reduce plaque formation
- ABCA1 protein within cell helps transfer cholesterol to HDL which is converted to ester by LCAT
what is the fate of mature HDL
- take up by liver via specific receptors
- cells requiring additional cholesterol can utilise scavenger receptor to get it from HDLs
- HDL can also exchange cholesterol ester for TAG with VLDL via cholesterol exchange transfer protein)
what is hyperlipoproteinaemia
high lipoproteins in blood
what are the two ways hyperlipoproteinaemia can be caused
- over production
- under removal
how many classes of hyperlipoproteinaemia are there
6
what are the signs of hyperlipoproteinaemia
- high blood cholesterol
- xanthelasma ( yellow particles eyelid)
- tendon xanthoma (nodules on tendon)
- corneal arcus (white/blue circle around eye)
what are the four types of treatment for hyperlipoproteinaemia
- diet (less cholesterol in diet more fibre)
- lifestyle (increase exercise)
- statins (inhibt HMG-CoA reductase)
- bile salt sequestrants (bind to bile salts to forces liver to produce more)
