Lipid Transport Flashcards
1
Q
How is lipid carried in the blood
A
- Hydrophobic molecules insoluble in water - need carriers to transport in blood
- 2% lipids carried bound to albumin but has limited capacity
- 98% of lipids are carried as lipoprotein particles consisting of phospholipid, cholesterol, cholesterol esters, free fatty acids
2
Q
What is the function of apolipoproteins
A
- apoB (VLDL, IDL, LDL) and apoAI (HDL) important
- Can be integral or peripheral of phospholipid bilayer
- Structural - packaging water insoluble lipid
- Functional - cofactor for enzymes, ligands for cell surface receptors
3
Q
Describe the structure of lipoproteins
A
- Surface coat (shell) and a hydrophobic core
- Surface coat contains phospholipids, cholesterol and apolipoproteins
- Hydrophobic core contains triacylglycerols and cholesterol esters
4
Q
What is the role of cholesterol and how is it transported in blood
A
- Some obtained from diet but most synthesised in liver
- Essential component of membranes to allow fluidity
- Precursor of steroid hormones (aldosterone, testosterone, cortisol, oestrogen)
- Precursor of bile acids
- Transported around body as cholesterol ester
5
Q
What are the classes of lipoproteins and their main function
A
- Chylomicrons - transport dietary triacylglycerol from intestine to tissues such as adipose tissue
- VLDL - transport of triacylglycerol synthesised in liver to adipose tissue for storage
- IDL - short lived precursor for LDL, transport of cholesterol synthesised in the liver to tissues
- LDL - transport of cholesterol synthesised in the liver to tissues
- HDL - transport of excess tissue cholesterol to liver for disposal as bile salts and to cells requiring additional cholesterol
6
Q
Explain the role of lipoprotein lipase in lipoprotein metabolism
A
- Responsible for removing core triacylglycerols from lipoprotein particles such as chylomicrons and VLDLs
- Found attaches to inner surface of capillaries in tissues such as adipose tissue and muscle
- Insulin increases synthesis
- Hydrolyses triacylglycerols to fatty acids and glycerol
7
Q
Explain the role of Lecithin: cholesterol acyltransferase (LCAT) in lipoprotein metabolism
A
- Removal of core lipids form lipoprotein particles makes them unstable as ratio of surface to core lipids increase
- LCAT converts surface lipid to core lipid to restore stability
- Deficiency results in abnormal structure and failure of lipid transport
8
Q
Explain how chylomicron metabolism occurs
A
- Loaded in small intestine and apoB-48 added before entering lymphatic system
- Involved in transport of dietary fat
- Enter bloodstream at thoracic duct which empties into left subclavian vein and acquires two new apoproteins once in blood
- apoC binds lipoprotein lipase on adipose cells and muscle
- Released fatty acids enter cells, depleting chylomicron of its fat content
- When triglyceride reduced to 20%, apoC dissociates and becomes chylomicron remnant
- Chylomicron remnant returns to liver and apoE binds to LDL receptor and taken up by receptor mediated endocytosis
9
Q
Explain VLDL metabolism
A
- Made in liver for transporting triacylglycerol to other tissues
- Apolipoproteins apoB100 added during formation and apoC and apoE added from HDL particles in blood
- VLDL binds to lipoprotein lipase and starts becoming depleted of triacylglycerol
- As VLDL is depleted, some VLDL particles dissociates from the LPL enzyme complex and return to liver
- Once VLDL is depleted beyond 30%, becomes IDL
- In muscle, the released fatty acids are used for energy production
- In adipose, the fatty acids are used for re-synthesis of triacylglycerol and storage
10
Q
Explain IDL and LDL metabolism
A
- IDL particles can also be taken up by liver or rebind to LPL enzyme to further deplete triacylglycerol content
- LDL particle has high cholesterol content as all triacylglycerol taken by tissue
- LDL mainly transports cholesterol to peripheral tissues
- Receptor mediated endocytosis - LDL taken up by cell and cholesterol release inside
- Cells requiring cholesterol synthesise LDL receptors
- LDL receptors unexposed when cholesterol inside to avoid overaccumulation
- LDL particles do not have apoC or apoE so are not efficiently cleared by liver
11
Q
Outline HDL metabolism
A
- Transport excess cholesterol from peripheral cells back to liver for metabolism
- Do not have cargo when leaving liver
- Synthesised in liver and intestine
- Can also bud off from chylomicrons and VLDL as they are digested by LPL
- HDL have ability to remove cholesterol from cholesterol-laden cells and return it to liver
- ABCA1 help load HDL with cholesterol in peripheral tissues (reverse cholesterol transport)
- Excess cholesterol can be converted into bile salts in the liver
- HDL can exchange cholesterol ester for TAG with VLDL via action of cholesterol exchange transfer protein (CETP)
12
Q
Explain how tissues obtain the lipids they require
A
- LDL responsible for delivering cholesterol to tissues
- Cells requiring cholesterol express LDL receptors in plasma membrane
- ApoB-100 on LDL acts as a ligand for these receptors
- Receptor/LDL complex taken into cell by receptor mediated endocytosis into endosomes
- Fuse with lysosomes for digestion to release cholesterol and fatty acid
13
Q
Explain the classification of hyperlipoproteinaemias
A
- Type 1 - defective lipoprotein lipase, no linked with coronary heart disease, chylomicrons in fasting plasma
- Type IIa - defect in LDL receptor - associated with coronary heart disease
- Type III - defective apoprotein (apoE - cannot enter liver), raised chylomicron remnants and IDL - associated with coronary heart disease
- Type IV - associated coronary disease
- Type V - raised chylomicrons and VLDL in fasting plasma - associated with coronary heart disease
14
Q
What are clinical signs of hyperlipiproteinaemias
A
- High level of cholesterol in blood
- Xanthelasma - yellow patches on eyelids
- Tendon xanthoma - nodules on tendon
- Corneal arcus - obvious white circle around eye
15
Q
Explain the pathogenesis of atherosclerosis
A
- Half life of LDL in blood is much longer, more susceptible to oxidative damage
- Oxidised LDL engulfed by macrophages
- Macrophages becomes saturated with LDL and becomes foam cells
- Accumulate in intima wall of blood vessels to form fatty streak
- Fatty streaks evolve into atherosclerotic plaque
- Grows and encroaches on the lumen of the artery leading to angina
- Could rupture and trigger acute thrombosis (clot)by activating platelets and clotting cascade
- Could cause stroke or MI
